Pottmes, Germany

  • Emovi 3D Knee Assessment Device Intervention for Operational Readiness

    The purpose of this study is to assess the effectiveness of using a 3D medical assessment device versus usual care to help guide clinical decisions about the management of PFP. The objective is to determine if gathering objective biomechanical data from a three-dimensional (3D) motion capture device leads to more precise and optimal care, ultimately improving physical function and other outcomes compared to participants who receive routine care that is not guided by information from this device. Participants will be recruited from primary care and physical therapy clinics at participating sites. Authorized study personnel will search electronic medical records (Genesis) to identify potential study participants diagnosed with knee pain. After consent and enrollment, participants will complete baseline measures and then receive a Knee Kinesiography exam. The participant will be entered into the KneeKG system using a unique participant identifier. After the knee kinesiography exam with the KneeKG, participants will be randomized 1:1 into one of two different treatment arms: 1) KneeKG informed care or 2) usual care without any information from the KneeKG. Knee mechanics during gait is assessed with a Knee Kinesiography exam. The participant will walk for 5 minutes on a commercial treadmill at their comfortable speed. Three-dimensional (3D) knee kinematics are captured on each leg using the KneeKG system (Emovi, Canada). With this validated FDA cleared medical device, there is an accurate quantification of specific knee biomechanical markers during gait in a clinical setting. There will be two 45-second trials to electronically capture the data which is immediately accessible through automatic reports. Biomechanical markers captured include but are not limited to varus/valgus alignment at stance, varus/valgus alignment at heel strike, knee flexion angle at heel strike, total knee excursion in sagittal plane, tibial rotation at heel strike and throughout gait cycle. The entire procedure will take approximately 15-20 minutes. This procedure will occur at baseline and also again at 12 weeks.

    Phase

    N/A

    Span

    54 weeks

    Sponsor

    Womack Army Medical Center

    Honolulu, Hawaii

    Recruiting

  • An Evaluation of Two PTSD Assessments in an Active Duty and Military Veteran Sample

    This is a randomized, observational study where participants will be randomized into one of the four study cohorts. The primary goals of this study are to establish the test-retest reliability of the CAPS-5 and the PSSI-5 and to compare these with each other (Cohorts 1 and 2), to test the convergent validity of the CAPS-5 against the PSSI (Cohort 3) and against the CAPS-IV (Cohort 4), and finally to investigate the consistency of response over 12 weeks on CAPS-5 (Cohort 1) and on the PSSI-5 (Cohort 2). In addition, on an exploratory level, possible biomarkers of PTSD and their relationship to each other and to diagnosis of PTSD will be evaluated. Participants will be 950 males and females recruited from the Cincinnati VA Medical Center (Cincinnati, OH), Trauma Recovery Center, and Tripler Army Medical Center (Honolulu, HI). the investigators anticipate that understanding the validity and reliability of the PSSI-5 and the CAPS-5 and the biomarkers related to PTSD will provide necessary information for care provided to active duty military and veterans suffering from PTSD. It will also directly inform trial designs and increase the likelihood of technical and regulatory success for new treatments for PTSD.

    Phase

    N/A

    Span

    324 weeks

    Sponsor

    U.S. Army Medical Research and Development Command

    Honolulu, Hawaii

    Recruiting

    Healthy Volunteers

  • Weight Loss and Physical Fitness Following Pregnancy in Active Duty Women

    RESEARCH BACKGROUND: Women naturally gain weight beyond that of the added pregnancy tissue and many gradually lose this excess weight following delivery. In the US, 15-27% of women across all ethnic groups have excess postpartum weight retention (PPWR) of > 10lbs one year after delivery. (Lipsky, Strawderman, and Olson 2012, 1496-1502); (Gunderson et al. 2008, 178-187); (DeGroot et al. 2021a, e0255248) This issue has also been documented in AD women across multiple services with 12-15% not meeting fitness standards at one year postpartum. (DeGroot et al. 2021b, e0255248) (Rogers et al. 2020, e227-e234) This is an immediate concern for AD women as it has a detrimental effect on career progression. Weight retention also has long-term consequences for health including contributing significantly to the risk of obesity, diabetes, heart disease and hypertension. It is shown that women who return to their pre-pregnancy weight by about six months have a lower risk of being overweight 10 years later. (Amorim Adegboye and Linne 2013, CD005627) This critical postpartum time period in a woman's life has major repercussions on her well-being. A significant number of women are never able to effectively lose weight and achieve fitness postpartum. Long-term, the added weight and resulting metabolic effects of postpartum weight retention lead to chronic health conditions such as obesity type II diabetes, chronic hypertension and other components of metabolic syndrome. (Linne et al. 2003, 1516-1522) Many AD women succumb to this cycle of weight retention and are unable to serve effectively in the military. This affects 10-20% of AD women who become pregnant while serving and was highlighted by retrospective research performed at Tripler Army Medical Center. (DeGroot et al. 2021a, e0255248) Our literature review reveals five factors that contribute significantly to weight changes following delivery in AD women: diet, exercise, breastfeeding, sleep and depression. RESEARCH GOALS AND OBJECTIVES: The PADaWL study seeks to determine if dietary interventions by a licensed dietician in the first year postpartum will lead to more effective weight loss and ultimately physical fitness than routine postpartum care among a cohort of AD service members. The primary goal of this research is to determine how effectively AD women lose weight and recover fitness after delivery. Specifically, aims of this study are to: Aim#1: Identify factors that influence the timing of active duty servicewomen return-to-duty fitness postpartum. Aim #2: Characterize the utility of a biometric device to monitor multi-factorial influences on achieving pre-pregnancy fitness postpartum Aim #3: Determine the effectiveness of intensive dietary counseling in the first year postpartum on weight loss and physical fitness. STUDY PROCEDURES: I. Recruitment will be performed using multiple methods and can be recruited at any time during their pregnancy: Passive recruitment will occur in the TAMC OB/GYN clinic. Posters will be displayed throughout the OB/GYN clinic with tabs showing phone numbers allowing the patients to contact researchers directly to inquire about the study. Active recruitment will occur in the TAMC OB/GYN clinic. Providers will directly ask AD women who are obstetric patients whether they are interested in participating and direct them to the research staff. If necessary, appointments in MHS Genesis will be screened for healthy primiparous AD women with an uncomplicated singleton pregnancy who would be candidates for the study. II. Screening for Eligibility: Potential participants will be approached and screened for inclusion and exclusion criteria by either one of the researchers or research assistants. This will be done via telephone call. If they are interested in participating in the study, they will be sent a flyer detailing the study via email. If they maintain interest in participating in the study, they will be asked to meet with the research team at the time of their 34-37week appointment. III. Enrollment: Eligible potential participants will meet a member of the research team either before or after their 34-37week appointment. They will bring a copy of their pre- pregnancy fitness report. During this appointment they will be rescreened. Informed Consent and HIPPA consent will be obtained. Randomization will occur. Subjects will be assigned a de-identified study subject number. An anonymous myfitnesspal.com account will be opened, and they will be asked to familiarize themselves with the website. Subjects will be asked to obtain a scale for home use. Subject will be given a hand- out on all the data which will be collected on her during the course of the study. IV. Data collection at Enrollment: After signing the consent, subjects will be asked to complete questionnaires on fitness and diet during their pregnancy. These questionnaires will be on-line, and they will enter their data utilizing their anonymous study ID. A demographic, cultural and social questionnaire will be obtained. V. Retrospective Data collected after Enrollment: Weight gain in pregnancy, Conditions complicating pregnancy, EPDS score at 28weeks VI. Delivery: All AD women participants in the PADaWL study coming to TAMC L&D for their delivery after 35 weeks will be identified based on the posted website list, via screening of patients on the postpartum ward, or will contact research personnel via telephone call or text. Lipid profile labs will be drawn at the time of their admission with the remainder of their obstetric labs. Subjects will deliver their newborn and after stabilization will be transferred to the postpartum ward. On postpartum day #1 or #2, the subject will be approached by the research team in the postpartum ward. Subjects will be given the Garmin fitness tracker and given instructions on use. The subject will use their initials and only their birthday year to set up the app. She will be asked to start recording diet and activity levels (primarily measured as steps and caloric expenditure) on the day after being discharged from hospital. She will be given repeat instructions on appropriate monitoring of diet and exercise. Before discharge she will obtain a 6-week postpartum appointment with one the researchers. Intervention group will obtain their first virtual nutrition counseling appointment to occur within the first month postpartum VII. Randomized groups to active vs routine dietary management: Both groups will receive the following: Nutrition education handouts pertaining to healthy postpartum eating, Nutrition education handouts pertaining to calorie counting procedures to include websites, apps, and methods of estimating caloric intake, General calorie recommendations based on participant age, height, weight, and activity level Intervention group will receive: One-on-one appointments with a Registered Dietitian via virtual health within the first month postpartum, three months postpartum, six months postpartum, and 12 months postpartum VIII. First 12 weeks postpartum: Period of intense data collection: All subjects will be collecting daily diet information via myfitnesspal.com. All subjects will be collecting activity as well as sleep levels via the Garmin fitness tracker. This data will be downloaded automatically to the website via their smart phone. All subjects will document her breast feeding weekly in the myfitnesspal.com app. All subjects will obtain weekly weights and place data onto their myfitnesspal.com website. The intervention group will have a virtual nutrition counseling appointment within the first month postpartum and a second appointment in the third month postpartum. At the 6- week postpartum appointment with one of the research investigators, subjects will submit a EPDS questionnaire to assess depression. This weekly data will be collected through their 12weeks postpartum. The data will be accessible by the research personnel via the internet. If data is missing, the subject will be contacted by research personnel to improve compliance. IX. 6 months postpartum: Subjects will undergo telephonic interview with research team. The following data will be obtained: Weight, Dietary questionnaire, Fitness questionnaire, Sleep questionnaire, EPDS, Breast feeding data, The intervention group will have a 3rd virtual nutrition counseling in this timeframe. X. 9 months postpartum: The intervention group will undergo a fourth and final virtual nutrition counseling appointment in this timeframe. XI. 12 months postpartum: The patient will undergo her first military fitness evaluation for record at 1 year postpartum including weight and height. She will be asked to bring a copy of these data to her 12month postpartum visit. XII. 12 months postpartum: Subjects will undergo a clinic visit with physical exam with one of the research investigators. In addition, they will submit the following data: Weight, Dietary questionnaire, Fitness questionnaire, Sleep questionnaire, EPDS, Breast feeding data, Post-study questionnaire. The intervention group will have a final virtual nutrition counseling appointment. STAISTICAL ANALYSIS Aim#1: The outcomes evaluated are 1) the ability of AD women to achieve military weight standards at 12 weeks, 6months and 1 year postpartum, and 2) improvement in mandated physical fitness assessment at 12 months postpartum. Odds ratio and t-test will be used to compare pre-pregnancy and postpartum fitness results for the collective enrollment. ANOVA with repeated measures over time will be used to evaluate differences between pre pregnancy, at delivery, and different time points post pregnancy for weight. Regression analysis will be used to determine the linear regression algorithm for weight loss over time for each participant from delivery through up to one year postpartum to determine the x intercept of the time point when weight equals pre pregnancy weight for each participant. This time period of return to pre pregnancy weight can be used along with percent weight loss at 12 weeks post pregnancy as the metrics to examine the relationship with other variables of sleep, breast feeding, activity, etc.Multiple variate stepwise regression analysis will be used to identify which variables most strongly independently influence weight loss (period of time before pre pregnancy weight is achieved, and/or percent weight loss at specific timepoints (1eg. 2 weeks, 6 months, 1 year) from delivery date). Which variables are covariates with other variables will also be determined. Aim #2: The efficacy of the fitness tracker to monitor postpartum women as they regain fitness in the year after pregnancy will be evaluated based on 1) the ability to generate consistent useable data, and 2) the acceptance by the study participants as a wearable device Descriptive statistics will be used to characterize how many events of interrupted data or non-collected data missing data occurs each week for 12 weeks postpartum Aim #3: Determine the effectiveness of intensive dietary counseling in the first year postpartum on weight loss and physical fitness. To test the effectiveness of dietary intervention the participants will be randomized to two groups. Group 1 (n=32) will receive routine postpartum care. Group 2 (n=32) will receive dietary interventions by a licensed dietician. The metric for efficacy of the intervention will be detecting an effect size of 20% in weight, sleep score, breast feeding score ANOVA will be used to compare the two groups with repeated measures over time at 16 time points over time (pre-pregnancy, time of delivery, weekly for 12 weeks, 6 months and 12 months postpartum) for weight, sleep score, breast feeding score. For fitness and activity ANOVA at two time points (pre-pregnancy and 12 months postpartum) by group interaction effect will be analyzed.

    Phase

    N/A

    Span

    119 weeks

    Sponsor

    Tripler Army Medical Center

    Honolulu, Hawaii

    Recruiting

    Healthy Volunteers

  • Trial to Evaluate Dietary Supplements to Maintain Gut Health During Travel

    Probiotics and passive immunoprophylaxis are classes of dietary supplements that are lawfully marketed in the US for maintenance of gut health (GH). This randomized, double-blind, clinical trial will evaluate one commercially available dietary supplement products (passive immunoprophylaxis (Travelan®), compared with placebo, to assess their ability to maintain normal gut function during travel. The results of this clinical trial will be used to evaluate the use of Travelan® to maintain GH during deployment and travel and is not intended to support a marketing application of any dietary supplement as a drug or biological product for human use. This study is a multi-site, randomized, placebo-controlled, double-blind clinical trial conducted on travelers and deployed US and United Kingdom (UK) military personnel. The study will test Travelan®, compared with placebo for maintenance of GH during and immediately after travel. Enrollment of 868 deployed military personnel or travelers will occur at sites within the Uniformed Services University of the Health Sciences (USU) Infectious Disease Clinical Research Program (IDCRP) network and the UK military. Subjects will be randomized to receive a masked regimen of Travelan® or placebo taken as 1 sachet twice daily with meals. Chemoprophylaxis will be started 2 days prior to arrival and maintained for a maximum duration of 20 days (minimum of 10 days) during travel or deployment. Stool smears collected during travel will be used for evaluating the microbiome and for gut pathogen identification. Paired (pre and post-supplement administration) sera and stool samples (pre- and post-supplement administration) will be collected for testing of exploratory objectives. Primary Endpoint (Efficacy): The primary efficacy endpoint is the combined endpoint of incidence of GH disruption (defined as 3 or more unformed stools in a 24-hour period) OR 2 or more unformed stools and one or more associated symptoms (nausea, vomiting, abdominal pain, fever, bloody stool) in a 24-hour period OR antibiotic treatment for diarrhea per subject report, during the period of prophylaxis. Primary endpoint data will be obtained from review of the Travel Diary. Secondary Objectives: Secondary endpoints will include an evaluation of compliance with each dietary supplement and tolerability (e.g. taste, bloating, flatulence, etc.); these will be assessed using the Travel Diary. Differences in GH associated enteropathogen distribution among the 2 treatment groups will be determined by testing stool smears collected by subjects during a GH deficit using a polymerase chain reaction (PCR) assay. Exploratory objectives related to changes in the gut microbiome with dietary supplement use and proteomic signatures of the host-pathogen interaction will be addressed contingent on the availability of additional funding.

    Phase

    N/A

    Span

    166 weeks

    Sponsor

    Henry M. Jackson Foundation for the Advancement of Military Medicine

    Honolulu, Hawaii

    Recruiting

    Healthy Volunteers

  • Active Surveillance, Bleomycin, Etoposide, Carboplatin or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors

    PRIMARY OBJECTIVES: I. To evaluate whether a strategy of complete surgical resection followed by surveillance can maintain an overall survival rate of at least 95.7% at two years for pediatric, adolescent and adult patients with stage I (low risk) malignant germ cell tumors, and at least 95% for patients with ovarian pure immature teratoma. II. To compare the event-free survival of a carboplatin versus (vs.) cisplatin-based regimen in the treatment of pediatric, adolescent and young adult patients with standard risk non-seminomatous germ cell tumors. IIa. To compare the event free survival (EFS) of a carboplatin-based regimen (carboplatin [C] etoposide [E] bleomycin [b]) vs. a cisplatin-based regimen (cisplatin [P]Eb) in children (less than 11 years in age) with standard risk germ cell tumors (GCT). IIb. To compare the EFS of a carboplatin-based regimen (BEC) vs. a cisplatin-based regimen (BEP) in adolescents and young adults (ages 11 - < 25 years) with standard risk GCT. SECONDARY OBJECTIVES: I. To compare the incidence of ototoxicity in children, adolescents and young adults with standard risk germ cell tumors treated with carboplatin-based chemotherapy as compared to cisplatin-based chemotherapy. II. To refine and validate a novel patient-reported measure of hearing outcomes for children, adolescents and young adults with standard risk germ cell tumors. EXPLORATORY OBJECTIVES: I. To prospectively determine the correlation of tumor marker decline (alpha-fetoprotein [FP] and beta-human chorionic gonadotropin [HCG]) with clinical outcome in low and standard risk germ cell tumor patients. II. To compare self-reported peripheral neuropathy and other patient-reported outcomes between children, adolescents and young adults with standard risk germ cell tumors treated with carboplatin-based chemotherapy as compared to cisplatin-based chemotherapy. III. Assess the relationship between hearing loss as measured by audiometry with the effects of tinnitus as assessed on the Adolescent and Young Adult Hearing Screening (AYA-HEARS) instrument. IV. To evaluate the prognostic significance of serum micro ribonucleic acid (miRNA)s in stage I testicular cancer (seminoma and non-seminoma) patients by collecting clinical data and serum specimens for future analysis. OUTLINE: Patients with low-risk stage I grade 2, 3 ovarian immature teratoma or stage I non-seminoma malignant germ cell tumors (MGCT)s undergo observation and can transfer to standard risk arm at time of recurrence if eligibility criteria are met. Patients with stage I seminoma testicular MGCT undergo observation, and those with residual/recurrent disease are treated at the discretion of their physician. Patients undergo computed tomography (CT), magnetic resonance imaging (MRI), and/or chest x-ray as well as blood sample collection throughout the trial to monitor for response and recurrence. Patients may also undergo a tumor biopsy throughout the trial. Patients with standard risk 1 are randomized into 1 of 2 arms. ARM I (CEb): Patients receive bleomycin intravenously (IV) over 10 minutes and carboplatin IV over 1 hour on day 1. Patients also receive etoposide IV over 1-2 hours on days 1-5. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and/or chest x-ray as well as blood sample collection throughout the trial. Patients may also undergo a tumor biopsy throughout the trial. Patients undergo a pulmonary function test on study. ARM II (PEb): Patients receive bleomycin IV over 10 minutes on day 1. Patients also receive etoposide IV over 1-2 hours and cisplatin IV over 1-3 hours on days 1-5. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and/or chest x-ray as well as blood sample collection throughout the trial. Patients may also undergo a tumor biopsy throughout the trial. Patients undergo a pulmonary function test on study. Patients with standard risk 2 are randomized into 1 of 2 arms. ARM III (BEC): Patients receive bleomycin IV over 10 minutes on days 1, 8, and 15, etoposide IV over 1-2 hours on days 1-5, and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and/or chest x-ray as well as blood sample collection throughout the trial. Patients may also undergo a tumor biopsy throughout the trial. Patients undergo a pulmonary function test on study. ARM IV (BEP): Patients receive bleomycin IV over 10 minutes on days 1, 8, and 15, etoposide IV over 1-2 hours on days 1-5, and cisplatin IV over 1-3 hours on days 1-5. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and/or chest x-ray as well as blood sample collection throughout the trial. Patients may also undergo a tumor biopsy throughout the trial. Patients undergo a pulmonary function test on study. After completion of study treatment, patients are followed up every 2 months for 12 months, every 3-6 months to 24 months, every 6 months for years 3-5, and then annually for up to 10 years.

    Phase

    3

    Span

    527 weeks

    Sponsor

    Children's Oncology Group

    Honolulu, Hawaii

    Recruiting

  • Project: Every Child for Younger Patients With Cancer

    PRIMARY OBJECTIVES: I. To maintain a Childhood Cancer Registry for infants, children, adolescents, and young adults with cancer. II. To utilize clinical and biological data to help determine eligibility or stratification, based on childhood cancer disease classification schemas, for potential enrollment of research subjects onto Children's Oncology Group (COG) therapeutic clinical trials. III. To develop a well annotated childhood cancer biorespository for current and future research through the collection of biospecimens (at diagnosis, time of progression, time of recurrence and/or post-mortem), including tumor, host and when feasible parental germline deoxyribonucleic acid (DNA); and key clinical data, including presentation, diagnostic, staging, summary treatment, and outcome information, from every child diagnosed with cancer at COG institutions. IV. To allow use of registry data for permission to be contacted in the future to consider participating in non-therapeutic and prevention research studies involving the child or their parents. OUTLINE: Patients undergo medical data review to create a Childhood Cancer Registry. Patients also undergo collection of biospecimen samples (e.g., tissue, blood, bone marrow, plasma, serum, buccal swab, saliva, cerebrospinal fluid, or urine).

    Phase

    N/A

    Span

    791 weeks

    Sponsor

    Children's Oncology Group

    Honolulu, Hawaii

    Recruiting

  • Risk-Based Therapy in Treating Younger Patients With Newly Diagnosed Liver Cancer

    PRIMARY OBJECTIVES: I. To estimate the event-free survival (EFS) in children with stage I (non-pure fetal histology [PFH], non-small cell undifferentiated [SCU]) and stage II (non-SCU) hepatoblastoma treated with surgical resection followed by 2 cycles of cisplatin, fluorouracil, and vincristine sulfate (C5V). II. To determine the feasibility and toxicity of adding doxorubicin hydrochloride to the chemotherapy regimen of C5V for children with intermediate-risk hepatoblastoma. III. To estimate the response rate to vincristine (vincristine sulfate), irinotecan (irinotecan hydrochloride), and temsirolimus in previously untreated children with high-risk, metastatic hepatoblastoma. IV. To determine whether timely (between diagnosis and end of second cycle of chemotherapy) consultation with a treatment center with surgical expertise in major pediatric liver resection and transplant can be achieved in 70% of patients with potentially unresectable hepatoblastoma. V. To foster the collection of tumor tissue and biologic samples to facilitate translational research and to provide data that may aid in risk-adapted approaches for subsequent clinical trials. SECONDARY OBJECTIVES: I. To estimate the EFS of patients with stage I PFH treated with surgery alone. II. To determine whether orthotopic liver transplantation (OLT) can be accomplished after successful referral and completion of 4 cycles of initial chemotherapy. III. To estimate the 2-year EFS for patients once identified as candidates for possible OLT, the 2-year EFS for patients referred to a transplant center that are resected without OLT, and the 2-year EFS for patients referred to a transplant center who receive OLT. IV. To register children with hepatoblastoma who receive OLT with PLUTO (Pediatric Liver Unresectable Tumor Observatory), an international cooperative registry for children transplanted for liver tumors. V. To determine if PRETEXT grouping can predict tumor resectability. VI. To monitor the concordance between institutional assessment of PRETEXT grouping and PRETEXT grouping as performed by expert panel review. VII. To estimate the proportion of stage IV patients who have surgical resection of metastatic pulmonary lesions. VIII. To determine the proportion and estimate the EFS of patients with potentially poor prognostic factors including alpha fetoprotein (AFP) < 100 ng/mL at diagnosis, microscopic positive surgical margins, surgical complications, multifocal tumors, microscopic vascular invasion, macrotrabecular histologic subtype, and SCU histologic subtype. OUTLINE: Patients are assigned to 1 of 4 treatment groups according to risk group. VERY LOW-RISK GROUP: Patients undergo surgery and receive no further treatment. LOW-RISK GROUP: (regimen T) Patients undergo surgery and then receive adjuvant cisplatin intravenously (IV) over 6 hours on day 1, fluorouracil IV on day 2, and vincristine sulfate IV on days 2, 9, and 16. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. INTERMEDIATE-RISK GROUP: (regimen F) Patients receive C5VD chemotherapy comprising cisplatin IV over 6 hours on day 1, fluorouracil IV on day 2, vincristine sulfate IV on days 2, 9, and 16, and doxorubicin hydrochloride IV over 15 minutes on days 1-2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo surgical resection after course 2 OR surgical resection or liver transplantation after course 4 of C5VD. HIGH-RISK GROUP: (regimen H) Patients receive up front VIT chemotherapy comprising vincristine sulfate IV on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5, and temsirolimus IV over 30 minutes on days 1 and 8. Treatment with VIT repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 4 courses of VIT in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity. Patients undergo tumor resection or liver transplant after course 4 of C5VD followed by 2 courses of adjuvant C5VD. After completion of study therapy, patients who receive chemotherapy are followed up periodically for at least 4 years.

    Phase

    3

    Span

    Sponsor

    National Cancer Institute (NCI)

    Honolulu, Hawaii

    Recruiting

  • Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia

    PRIMARY OBJECTIVES: I. To determine if the administration of post-Induction age-adjusted intrathecal triple therapy (ITT) on a Modified Berlin-Frankfurt-Munster (MBFM) interim maintenance (IM) high-dose methotrexate (IMHDM) backbone will improve 5-year disease-free survival (DFS) of children with high-risk (HR) B-acute lymphoblastic leukemia (ALL) compared to age-adjusted intrathecal (IT) methotrexate (MTX). II. To determine, in a randomized fashion, if the cyclophosphamide + etoposide containing regimen (Experimental Arm 1) will improve the 4-year DFS of children, adolescents, and young adults with very high-risk (VHR) B-ALL compared to a modified MBFM-IMHDM regimen that contains a second IM (Control Arm). SECONDARY OBJECTIVES: I. To determine the toxicity and tolerability of post-Induction age-adjusted ITT compared to age-adjusted IT MTX in children with HR B-ALL. II. To determine the toxicity and tolerability of Experimental Arm 1 compared to the Control Arm in children, adolescents, and young adults with VHR B-ALL. III. To determine whether a single-arm, modified Induction with limited anthracycline exposure and post-Induction therapy regimen with MBFM-IMIDM and reduced vincristine (vincristine sulfate)/steroid pulse frequency and enhanced supportive care in children with Down syndrome (DS) and HR B-ALL will result in a >= 65% 5-year DFS and < 10% Induction mortality. IV. To determine the toxicity and tolerability of MBFM-IMIDM in children with DS and HR B-ALL. V. To estimate overall survival (OS) rates both overall and by regimen a) for HR B-ALL and b) VHR B-ALL patients. VI. To determine the incidence of osteonecrosis (ON), defined by magnetic resonance (MR) imaging, and to characterize the natural history of clinically silent ON in children, adolescents, and young adults 10 years of age and greater and to assess the role of drugs (i.e., asparaginase and methotrexate) in addition to corticosteroids, in the risk for development of ON. VII. To determine if the prevalence of cognitive deficits measured by CogState, in children (ages 6 to 11 years) with HR- and VHR B-ALL at 1 year off therapy, is significantly higher than the normative population (> 14%) in the following domains: working memory, executive function, visual motor, processing speed, and visual attention. TERTIARY OBJECTIVES: I. To determine if the reduction of minimal residual disease (MRD) from end-Induction to end-Consolidation is greater for children, adolescents, and young adults with VHR B-ALL receiving Experimental Arm 1 compared to the Control Arm. OUTLINE: INDUCTION THERAPY: Patients without Down syndrome receive induction chemotherapy comprising cytarabine intrathecally (IT) on day 1; vincristine sulfate intravenously (IV) over 1 minute on days 1, 8, 15, and 22; daunorubicin hydrochloride IV over 1-15 minutes on days 1, 8, 15, and 22; dexamethasone orally (PO) or IV twice daily (BID) on days 1-14 (patients under 10 years old) or prednisone PO or IV BID on days 1-28 (patients at least 10 years old); pegaspargase IV over 1-2 hours on day 4; and methotrexate IT on days 8 and 29 (plus days 15 and 22 for CNS3 patients). Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. CONSOLIDATION THERAPY: Patients are randomized to 1 of 2 treatment arms. ARM I HR B-ALL CONSOLIDATION (C): Patients receive consolidation therapy comprising cyclophosphamide IV over 30-60 minutes on days 1 and 29; cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO once daily (QD) on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22; vincristine sulfate IV over 1 minute on days 15, 22, 43, and 50; and pegaspargase IV over 1-2 hours on days 15 and 43. Patients with continuing clinical evidence of testicular leukemia undergo radiotherapy (RT) QD, 5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. ARM II HR B-ALL C: Patients receive Consolidation therapy as in Arm I HR B-ALL C. Patients also receive ITT comprising methotrexate, hydrocortisone sodium succinate, and cytarabine on days 1, 8, 15, and 22. Patients with testicular leukemia also undergo RT as in Arm I HR B-ALL C. INTERIM MAINTENANCE THERAPY: ARM I HR B-ALL INTERIM MAINTENANCE (IM): Patients receive IM therapy comprising vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; methotrexate IT on days 1 and 29; and mercaptopurine PO on days 1-56. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity. ARM II HR B-ALL IM: Patients receive ITT on days 1 and 29 and IM therapy as in Arm I HR-ALL IM. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity. DELAYED INTENSIFICATION THERAPY: ARM I HR B-ALL DELAYED INTENSIFICATION (DI): Patients receive DI therapy comprising vincristine sulfate IV over 1 hour on days 1, 8, 15, 43, and 50; dexamethasone PO or IV BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-60 minutes on days 1, 8, and 15; methotrexate IT on days 1, 29, and 36; pegaspargase IV over 1-2 hours on days 4 and 43; cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO QD on days 29-42. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. ARM II HR B-ALL DI: Patients receive ITT on days 1, 29, and 36 and DI therapy as in Arm I HR B-ALL DI. MAINTENANCE (M) THERAPY: ARM I HR B-ALL M: Patients receive maintenance therapy comprising vincristine sulfate IV over 1 minute on days 1, 29, and 57; methotrexate IT on day 1 (also day 29 of courses 1-4); prednisone PO BID on days 1-5, 29-33 (may receive methylprednisolone IV if PO is not tolerated), and 57-61; mercaptopurine PO QD on days 1-84; and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicity. ARM II HR B-ALL M: Patients receive ITT on day 1 (also day 29 of courses 1-4) and maintenance therapy as in Arm I HR B-ALL M. Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicity. VERY HIGH-RISK B-ALL: Patients are randomized to 1 of 3 treatment arms. CONSOLIDATION THERAPY PART I: In all arms, patients receive cyclophosphamide IV over 30-60 minutes on day 1; cytarabine IV or SC on days 1-4 and 8-11; mercaptopurine PO QD on days 1-14; methotrexate IT on days 1, 8, 15, and 22 (days 1 and 8 only for CNS3 patients); vincristine sulfate IV over 1 minute on days 15 and 22; and pegaspargase IV over 1-2 hours on day 15. Patients with continuing clinical evidence of testicular leukemia undergo RT QD, 5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. CONSOLIDATION THERAPY PART II: ARM A VHR B-ALL C (CONTROL ARM): Patients receive consolidation therapy comprising cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; mercaptopurine PO QD on days 29-42; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. ARM B VHR B-ALL C (EXPERIMENTAL ARM): Patients receive consolidation therapy comprising cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 60-120 minutes on days 29-33; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. ARM C VHR B-ALL C: Patients receive clofarabine IV over 2 hours on days 29-33 and consolidation therapy as in Arm B VHR B-ALL C. (Closed as of 9/12/2014) INTERIM MAINTENANCE I: In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; mercaptopurine PO QD on days 1-56; and methotrexate IT on days 1 and 29. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity. DELAYED INTENSIFICATION PART I: In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 8, and 15; dexamethasone PO or IV BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-60 minutes on days 1, 8, and 15; methotrexate IT on day 1; and pegaspargase IV over 1-2 hours on day 4. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. DELAYED INTENSIFICATION PART II: ARM A VHR B-ALL DI (CONTROL ARM): Patients receive DI therapy comprising cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; thioguanine PO QD on days 29-42; methotrexate IT on days 29 and 36; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. ARM B VHR B-ALL DI (EXPERIMENTAL ARM): Patients receive DI therapy comprising cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 60-120 minutes on days 29-33; methotrexate IT on days 29 and 36; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. ARM C VHR B-ALL DI: Patients receive clofarabine IV over 2 hours on days 29-33 and DI therapy as in Arm II B VHR B-ALL DI. (Closed as of 9/12/2014) INTERIM MAINTENANCE II: In all arms, patients receive vincristine sulfate IV over 1 minute and methotrexate IV over 2-5 minutes (undiluted) or 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41; pegaspargase IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. MAINENTANCE THERAPY: Patients with CNS3 disease at diagnosis undergo RT QD over 4 weeks (10 fractions total). In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61 (may receive methylprednisolone IV if PO is not tolerated); methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (except on methotrexate IT days); mercaptopurine PO QD on days 1-84; methotrexate IT on day 1 (also day 29 of courses 1 and 2 for CNS patients who did not undergo RT). Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicities. INDUCTION THERAPY: All patients receive cytarabine IT on day 1; vincristine sulfate IV over 1 minute on days 1 and 8, dexamethasone PO or IV BID (patients under 10 years old) or prednisone PO BID (patients at least 10 years old) on days 1-14 (may receive methylprednisolone IV if PO is not tolerated), pegaspargase IV over 1-2 hours on day 4; methotrexate IT on day 8; and leucovorin calcium PO on days 10-11. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity. Rapid early responders (RER): Patients receive induction therapy comprising vincristine sulfate IV over 1 minute on days 15 and 22; dexamethasone PO BID or prednisone PO BID on days 15-28; methotrexate IT on day 29 (also days 15 and 22 for CNS3 patients); and leucovorin calcium PO on days 31-32 (also days 17-18 and 24-25 for CNS3 patients). Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity. Slow early responders (SER): Patients receive daunorubicin hydrochloride IV over 1-15 minutes on day 15 and Induction therapy as RER patients. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity. CONSOLIDATION THERAPY: All patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29; cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO QD on days 1-14 and 29-42; vincristine sulfate IV over 1 minute on days 15, 22, 43, and 50; pegaspargase IV over 1-2 hours on days 15 and 43; methotrexate IT on days 1, 8, 15, and 22 (days 1 and 8 only for CNS3 patients); and leucovorin calcium PO on days 3-4, 10-11, 17-18, and 24-25. Patients with continuing clinical evidence of testicular leukemia undergo RT QD, 5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. INTERIM MAINTENANCE THERAPY: Patients receive vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; intermediate dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; mercaptopurine PO QD on days 1-56; and methotrexate IT on days 1 and 29. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity. DELAYED INTENSIFICATION THERAPY: Patients receive vincristine sulfate IV over 1 minute on days 1, 8, 15, 43, and 50; dexamethasone PO BID or IV on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-60 minutes on days 1, 8, and 15; pegaspargase IV over 1-2 hours on days 4 and 43; cyclophosphamide IV over 30-60 minutes on day 29; thioguanine PO QD on days 29-42; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; methotrexate IT on days 1, 29, and 36; and leucovorin calcium PO on days 3-4, 31-32 and 38-39. MAINTENANCE THERAPY: Patients with CNS3 disease undergo RT QD, 5 days a week, for 2 weeks (10 fractions total). Patients receive vincristine sulfate IV over 1 minute on day 1; prednisone PO BID or IV on days 1-5 (may receive methylprednisolone IV if PO not tolerated); methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO QD on days 1-84; and methotrexate IT on day 1 (also day 29 of courses 1-4 for CNS3 patients who did not undergo RT). Treatment repeats every 12 weeks for 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for 10 years.

    Phase

    3

    Span

    Sponsor

    Children's Oncology Group

    Honolulu, Hawaii

    Recruiting

  • Biomarkers in Tumor Tissue Samples From Patients With Newly Diagnosed Neuroblastoma or Ganglioneuroblastoma

    PRIMARY OBJECTIVES: I. To prospectively analyze the factors that are currently used for risk-group assignment (v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog [MYCN] copy number by fluorescent in situ hybridization [FISH], deoxyribonucleic acid [DNA] content by flow cytometry, and tumor histology using the International Neuroblastoma Pathologic Classification System) in neuroblastoma tumors at the time of diagnosis. II. To maintain a reference bank containing clinically and genetically characterized frozen tumor tissue, tumor DNA and ribonucleic acid (RNA), histology slides and paraffin blocks, neuroblastoma-derived cell lines, patient serum and paired normal DNA obtained at the time of diagnosis, at the time of second-look surgery and at the time of relapse for future research studies. III. To prospectively analyze 1p, 11q, 14q and 17q allelic status, MYCN copy number by quantitative polymerase chain reaction (PCR); and the expression pattern of neurotrophin-related genes in diagnostic neuroblastoma tumors, and assay for the presence of rare tumor cells in biological specimens by reverse transcription (RT)-PCR; these biological variables will be analyzed for independent clinical significance compared to MYCN amplification, International Neuroblastoma Staging System (INSS) stage, age, ploidy, and histologic variables in predicting either response to treatment or outcome. IV. To build a database of the known biologic prognostic factors for patients on therapeutic studies. V. To serve as a Registry for neuroblastoma patients whose tumors demonstrate clinical and genetic features defined as ?Low Risk? for treatment failure in the absence of adjuvant therapy. SECONDARY OBJECTIVES: I. To prospectively analyze the concordance between detection of MYCN amplification in tumor samples and quantitative detection of MYCN DNA in serum, and to analyze the prognostic significance of MYCN amplification as detected in serum samples. II. To build a database that includes information regarding the presentation and natural history of neuroblastoma-associated health problems including but not limited to opsoclonus myoclonus ataxia (OMA) and/or spinal cord compression. OUTLINE: Patients undergo collection of blood, tissue, and bone marrow samples for analysis via RT-PCR, quantitative PCR, flow cytometry, and FISH. After completion of study, patients are followed up periodically.

    Phase

    N/A

    Span

    Sponsor

    Children's Oncology Group

    Honolulu, Hawaii

    Recruiting

  • Patient Retrospective Outcomes (PRO)

    This study is a retrospective, multi-center, de-identified patient data review. The study will include multiple independent cohorts to evaluate clinical outcomes in different subgroups.

    Phase

    N/A

    Span

    978 weeks

    Sponsor

    Boston Scientific Corporation

    Honolulu, Hawaii

    Recruiting

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