Mt. Gilead, Ohio

Product Surveillance Registry

Preventing Relapse of Problem Behavior Through Behavioral Economics: A Translational Analysis

Behavioral treatments can be an effective means to treat problem behavior. One of the most common behavioral treatments is differential reinforcement of alternative behavior, frequently implemented as functional communication training. Most demonstrations of behavioral treatments, including functional communication training, are conducted in highly controlled settings by trained therapists. When these treatments are implemented in community settings (e.g., an individual's home) by caregivers, they will be challenged, which can lead to the recurrence and sustained relapse of problem behavior. Recurrence and relapse can be the first step in a chain that leads to treatment failure. Fortunately, some tactics have been designed to sustain treatment effectiveness and mitigate two forms of relapse (i.e., resurgence and renewal) that result from two of three primary treatment challenges. These tactics function as inoculation (i.e., make problem behavior less likely to return). However, there are no tactics designed to specifically mitigate a third form of relapse: reinstatement This project involves a novel inoculation tactic to mitigate reinstatement and protect against the third common treatment challenge: extinction errors. The tactic in question is based on substantial conceptual and empirical evidence from behavioral economics, as well as the investigators' pilot work. The project uses an innovative translational-treatment model to better understand which of the proposed tactics (our novel tactic or the default standard-of-care approach) better inoculates against extinction errors through real-world analogues. The use of a translational-treatment model is consistent with other research examining the role of basic processes in behavioral treatment when collateral effects are unknown, and will also engender a thorough examination of the proposed tactics. In Aim 1, investigators will establish a proxy response, apply treatment to that proxy response, and examine the effectiveness of progressive ratio training in inoculating against extinction errors and mitigating response-dependent reinstatement. In Aim 2, investigators will establish a proxy response, apply treatment to that proxy response, and examine the effectiveness of progressive ratio training in inoculating against extinction errors and mitigating response-independent reinstatement. Outcomes of this research could improve the current standard of care for behavioral treatments to make them more effective in community application, result in the development and validation of novel inoculation tactics, and significantly improve the lives of individuals with IDD.

Lenalidomide, and Dexamethasone With or Without Daratumumab in Treating Patients With High-Risk Smoldering Myeloma

PRIMARY OBJECTIVES: I. To compare overall survival in patients with high-risk smoldering multiple myeloma randomized to daratumumab-lenalidomide (revlimid)-dexamethasone or revlimid-dexamethasone. SECONDARY OBJECTIVES: I. To compare progression-free survival and response rates between arms. II. To evaluate safety and compare toxicity rates between arms. III. To monitor incidence of infusion-related reactions over the first cycle of daratumumab. IV. To evaluate stem cell mobilization failure and early stem cell mobilization feasibility. EXPLORATORY OBJECTIVES: I. To measure treatment exposure and adherence. II. To estimate treatment duration and time to progression. PATIENT-REPORTED OUTCOMES OBJECTIVES: I. To compare change in health-related quality of life (Functional Assessment of Cancer Therapy [FACT]- General [G]]) from baseline to end of study therapy between arms. II. To compare change in FACT-G scores from treatment end to 6-months post-treatment end between arms. III. To describe changes in FACT-G scores over study therapy and shortly after treatment discontinuation and evaluate correlation with survival. IV. To evaluate attributes of select patient reported treatment-emergent symptomatic adverse events (Patient Reported Outcomes [PRO]-Common Terminology Criteria for Adverse Events [CTCAE]) longitudinally. V. To derive an overall PRO-CTCAE score at each assessment time point. VI. To measure the likelihood of medication adherence (ASK-12) at 6 month intervals throughout treatment. VII. To assess the association of overall PRO-CTCAE score with FACT-G score. VIII. To compare select PRO-CTCAE items and related provider-reported CTCAEs. IX. To evaluate association between treatment adherence and Adherence Starts with Knowledge 12 (ASK-12) score. X. To assess correlation of treatment adherence and ASK-12 score with FACT-G score. XI. To tabulate PRO compliance and completion rates. LABORATORY OBJECTIVES: I. To compare minimal residual disease negative rate after 12 cycles of study therapy between arms. II. To compare minimal residual disease (MRD) positive to negative conversion rates from 12 cycles to end of treatment between arms. III. To examine patterns of change in minimal residual disease levels during study therapy. IV. To evaluate agreement and discordance between methods determining disease-free status. V. To assess the prognostic value of minimal residual disease status at 12 cycles for overall and progression-free survival. IMAGING OBJECTIVES: I. To evaluate the association of baseline fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging with progression-free survival. II. To assess the ability of baseline FDG-PET/CT to predict minimal residual disease status after 12 cycles of study therapy and at the end of study therapy. III. To describe the results of subsequent FDG-PET/CT imaging studies in the subset of patients with baseline abnormal FDG-PET/CT, and to associate these results with progression-free survival (PFS). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive daratumumab intravenously (IV) on days 1, 8, 15, and 22 of courses 1-2, days 1 and 15 of courses 3-6, and day 1 of courses 7-24. Patients also receive lenalidomide orally (PO) daily on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22 in courses 1-12. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive lenalidomide PO daily on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22 of courses 1-12. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. After completion of study, patients will be followed up every 3, 6 or 12 months for up to 15 years from study entry.

Bupropion to Reduce Cancer Related Fatigue in Cancer Survivors

PRIMARY OBJECTIVE: I. To determine the efficacy of bupropion hydrochloride controlled-release (bupropion) versus placebo in reducing fatigue in a double-blinded, placebo-controlled, randomized clinical trial of cancer survivors with fatigue. SECONDARY OBJECTIVES: I. To assess the efficacy of bupropion versus placebo on depression and quality of life in cancer survivors with fatigue. II. To assess the tolerability of bupropion in cancer survivors with fatigue. EXPLORATORY OBJECTIVES: I. To assess the efficacy of bupropion versus placebo on symptomatology and cognition in cancer survivors with fatigue. II. To explore the effects of bupropion on putative mechanisms of cancer-related fatigue. III. To explore associations of CYP2B6 genotype with bupropion metabolism and changes in fatigue. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive bupropion hydrochloride controlled-release orally (PO) once daily (QD) for up to 13 weeks in the absence of unacceptable toxicity. Patients also undergo blood sample collection throughout study. ARM II: Patients receive placebo PO QD for up to 13 weeks in the absence of unacceptable toxicity. Patients also undergo blood sample collection throughout study.

Lung-MAP: A Master Screening Protocol for Previously-Treated Non-Small Cell Lung Cancer

Primary Objective of the Master Protocol (LUNGMAP) The primary objective of this screening study is to test patient specimens to determine eligibility for participation in the biomarker-driven and non-matched sub-studies included within the Lung-MAP umbrella protocol. Secondary Objectives 1. Screening Success Rate Objective To evaluate the screen success rate defined as the percentage of screened patients that register for a therapeutic sub-study. Screen success rates will be evaluated for the total screened population and by the subset of patients screened following progression on previous therapy or pre-screened on current therapy. 2. Translational Medicine Objectives 1. To evaluate circulating tumor DNA (ctDNA) and compare to the FMI Foundation tissue molecular profiling results in patients who submit a new biopsy for screening. 2. To establish a tissue/blood repository. Ancillary Study S1400GEN Objectives The Lung-MAP Screening Study includes an ancillary study evaluating patient and physician attitudes regarding the return of somatic mutation findings suggestive of a germline mutation. Participation in this study is optional. 1. Primary Objective To evaluate patient attitudes and preferences about return of somatic mutation findings suggestive of a germline mutation in the Lung-MAP Screening Study. 2. Secondary Objectives 1. To evaluate Lung-MAP study physician attitudes and preferences about return of somatic mutation findings suggestive of a germline mutation in the Lung-MAP Screening Study. 2. To evaluate Lung-MAP patients' and study physicians' knowledge of cancer genomics. 3. To evaluate Lung-MAP patients' and study physicians' knowledge of the design of the Lung-MAP Screening Study. 4. To explore whether physician and patient knowledge of cancer genomics and attitudes and preferences about return of genomic profiling findings are correlated.

Using Biomarkers to Help Guide Safe Immunotherapy Discontinuation in Patients With Unresectable Stage IIIB-IV Melanoma, The PET-Stop Trial

PRIMARY OBJECTIVE: I. To determine the 12 month event free survival (EFS) rate following discontinuation of anti-PD-1 therapy in patients with disease control and negative fludeoxyglucose F-18 (FDG)- positron emission tomography (PET)/computed tomography (CT) scan or biopsy for residual disease after 12 months of anti-PD-1 therapy (Arm A). SECONDARY OBJECTIVES: I. To determine rates of pathologic response in patients with tumor biopsies where positive hypermetabolic activity was present on FDG-PET/CT scan after 12 months of anti-PD-1 therapy (Arm B). II. To determine the overall 24 month EFS. III. To determine overall survival from start of anti-PD-1 therapy. IV. To determine percentage for patients who remain on treatment beyond 12 months because of positive FDG-PET/CT scan and positive biopsy for residual disease (or unable to obtain a biopsy). V. To determine incidence rates of treatment-related adverse events beyond 12 months from start of treatment in patients who discontinue anti-PD-1 therapy at 12 months and in patients who continue anti-PD-1 therapy beyond 12 months (Arm A versus [vs.] Arm B). EXPLORATORY OBJECTIVES: I. To assess agreement in determining FDG-PET/CT positivity between the local site read and central review. II. To determine if metabolic response on serial FDG-PET/CT from pre-therapy to 12 months of anti-PD-1 therapy, as determined centrally by various criteria, is associated with EFS. III. To determine if metabolic response on serial FDG-PET/CT from 12 to 24 months after start of anti-PD-1 therapy, as determined centrally by various criteria, is associated with EFS. BIOMARKER OBJECTIVE: I. To bank tumor samples and peripheral blood for future biomarker studies. OUTLINE: Patients continue their standard of care anti-PD-1 therapy and are then assigned to 1 of 2 arms. STANDARD OF CARE: Treatment may consist of the following regimens: 1) nivolumab intravenously (IV) over 30 minutes every 2 weeks (Q2W) or every 4 weeks (Q4W); 2) pembrolizumab IV over 30 minutes every 3 weeks (Q3W) or every 6 weeks (Q6W); 3) nivolumab IV over 30 minutes and ipilimumab IV Q3W for 4 doses followed by nivolumab IV over 30 minutes Q2W or Q4W; or 4) pembrolizumab IV over 30 minutes and ipilimumab IV Q3W for 4 doses followed by pembrolizumab IV over 30 minutes Q3W or Q6W. Treatment continues until 52 weeks from start of standard of care anti-PD-1 therapy in the absence of disease progression or unacceptable toxicity. ARM A: Patients with a negative FDG-PET/CT scan or a positive FDG-PET/CT scan but with a negative biopsy for viable tumor discontinue the anti-PD-1 therapy and undergo active surveillance. ARM B: Patients with a positive FDG-PET/CT scan and positive biopsy for viable tumor or a positive FDG-PET/CT scan and biopsy not performed continue their standard of care anti-PD-1 therapy for 12 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up through week 97 and then every 3 months for up to 5 years.

Testing the Use of Combination Therapy in Adult Patients With Newly Diagnosed Multiple Myeloma, the EQUATE Trial

PRIMARY OBJECTIVE: I. To determine if bortezomib, daratumumab and hyaluronidase-fihj (daratumumab), lenalidomide and dexamethasone (Btz-DRd) consolidation followed by daratumumab and lenalidomide (DR) maintenance after standard induction therapy with daratumumab, lenalidomide and dexamethasone (DRd) results in superior overall survival compared to DRd consolidation followed by DR maintenance, in minimal residual disease (MRD) positive patients. SECONDARY OBJECTIVES: I. To determine if Btz-DRd consolidation followed by DR maintenance after standard induction therapy with DRd results in superior overall survival compared to DRd consolidation followed by DR maintenance in MRD negative patients. II. To determine if Btz-DRd consolidation followed by DR maintenance after standard induction therapy with DRd results in superior progression-free survival compared to DRd consolidation followed by DR maintenance in both MRD positive and MRD negative patients. III. To describe and compare the incidence of toxicities during consolidation between Btz-DRd and DRd arms. IV. To assess the improvement in MRD negative rate with consolidation among patients who are MRD positive after induction. V. To assess the sustained MRD negative rate among patients who are MRD negative after induction. PATIENT REPORTED OUTCOMES (PRO) OBJECTIVES: I. To quantify the extent to which the addition of bortezomib to DRd over consolidation treatment contributes to neuropathy and associated physical and functional impairments. (Primary PRO Objective) II. To evaluate the rate of resolution of neurotoxicity and associated physical and functional impairments following completion of consolidation therapy. (Secondary PRO Objective) III. To investigate the relationship between MRD status and patient reported health-related quality of life outcomes. (Exploratory PRO Objective) IV. To evaluate attributes of select patient reported treatment-emergent symptomatic adverse events (PRO- Common Terminology Criteria for Adverse Events [CTCAE]) longitudinally and compare responses with provider-reported adverse events. (Exploratory PRO Objective) V. To tabulate PRO compliance and completion rates. (Exploratory PRO Objective) IMAGING OBJECTIVES: I. To evaluate the association between post-induction fludeoxyglucose F-18 (18F-FDG) positron emission tomography (PET)/computed tomography (CT) and patient outcomes (overall survival [OS] and progression-free survival [PFS]). (Primary Imaging Objective) II. To evaluate the association between baseline 18F-FDG PET/CT and patient outcomes (PFS and OS). (Secondary Imaging Objective) III. To compare overall survival with the addition of Bortezomib to consolidation DRd therapy among 18F-FDG PET/CT-positive and 18F-FDG PET/CT-negative subgroups. (Secondary Imaging Objective) IV. To evaluate the ability of baseline 18F-FDG PET/CT to predict post-induction depth of response as measured by MRD assessment. (Secondary Imaging Objective) V. To evaluate the ability of post-induction 18F-FDG PET/CT to predict MRD conversion post-consolidation. (Secondary Imaging Objective) VI. To utilize 18F-FDG PET/CT, standard risk factors and clinical data to identify distinct subgroups with differing patient outcomes (PFS and OS). (Exploratory Imaging Objective) VII. To compare the various qualitative 18F-FDG PET/CT criteria to determine which criteria yields superior risk stratification. (Exploratory Imaging Objective) OUTLINE: ARM A (INDUCTION): All patients receive standard induction therapy comprising the following: daratumumab subcutaneously (SC) on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7-9, lenalidomide orally (PO) daily on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity. After completion of standard induction therapy, patients are randomized to 1 of 2 arms. ARM B: CONSOLIDATION: Patients receive bortezomib SC on days 1, 8, and 15, daratumumab SC on day 1, lenalidomide PO daily on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive lenalidomide PO daily on days 1-21 and daratumumab SC on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM C: CONSOLIDATION: Patients receive daratumumab SC on day 1, lenalidomide PO daily on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive lenalidomide PO daily on days 1-21, and daratumumab SC on day 1. Cycles repeats every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, every 6 months if 2-5 years from study entry, then annually for up to 15 years from study entry.

Testing the Addition of Radiotherapy to the Usual Treatment (Chemotherapy) for Patients With Esophageal and Gastric Cancer That Has Spread to a Limited Number of Other Places in the Body

PRIMARY OBJECTIVE: I. To establish superiority of consolidative radiation therapy over continuation of systemic therapy alone in patients with oligometastatic esophageal and gastric adenocarcinoma (EGA) that does not progress on first-line therapy. OUTLINE: STEP 1 (INDUCTION PHASE): Patients are assigned to 1 of 2 arms. ARM A: Patients receive oxaliplatin intravenously (IV) over 1.5 hours, leucovorin IV over 1.5 hours, and 5-fluorouracil IV over 46-48 hours on days 1 and 15. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive oxaliplatin IV over 2 hours on day 1 and capecitabine orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. STEP 2: Patients are randomized to 1 of 4 arms. ARM C: One week post induction of patients in ARM A, patients undergo radiation therapy for up to 15 days. Within 2-4 weeks post radiation therapy, patients receive oxaliplatin, leucovorin, and 5-fluorouracil as in Arm A for 2 years in the absence of disease progression or unacceptable toxicity. ARM D: Post induction of patients in ARM A, patients continue oxaliplatin, leucovorin, and 5-fluorouracil as in Arm A for 2 years in the absence of disease progression or unacceptable toxicity. ARM E: One week post induction of patients in ARM B, patients undergo radiation therapy for up to 15 days. Within 2-4 weeks post radiation therapy, patients receive oxaliplatin and capecitabine as in Arm B for 2 years in the absence of disease progression or unacceptable toxicity. ARM F: Post induction of patients in ARM B, patients continue oxaliplatin and capecitabine as in Arm B for 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for up to 5 years from study entry. Patients experiencing disease progression are followed up every 3 months in years 1-2, and then every 6 months for up to 5 years from study entry.

Ramucirumab and Paclitaxel or FOLFIRI in Advanced Small Bowel Cancers

PRIMARY OBJECTIVES: I. To evaluate whether progression-free survival (PFS) meets an efficacy threshold in patients with previously treated advanced small bowel adenocarcinoma who receive treatment with ramucirumab and paclitaxel or FOLFIRI. II. If the stated threshold is met in both arms, to choose the better regimen with respect to progression free survival (PFS). SECONDARY OBJECTIVES: I. To assess overall response rate (ORR) [complete and partial, confirmed and unconfirmed] in the subset of patients with measurable disease treated with ramucirumab and paclitaxel or FOLFIRI in this patient population. II. To assess overall survival (OS) in patients treated with ramucirumab and paclitaxel or FOLFIRI in this patient population. III. To evaluate safety and toxicity associated with combination ramucirumab and paclitaxel treatment or FOLFIRI therapy in this patient population. TRANSLATIONAL OBJECTIVES: I. To explore the correlation of maximum decrease in CEA levels and time to maximum decrease in CEA levels with PFS, OS, and ORR. II. To bank tissue and blood samples for other future correlative studies from patients enrolled on the study. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive ramucirumab intravenously (IV) over 30-60 minutes on days 1 and 15, and paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive irinotecan IV over 90 minutes on days 1 and 15, leucovorin IV over 2 hours on days 1 and 15, and fluorouracil IV bolus on days 1 and 15. Patients also receive fluorouracil IV over 46-48 hours on days 1-3 and 15-17. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients completing study treatment are followed up every 8 weeks until disease progression. Once the disease has progressed, patients are followed up every 6 months for up to 3 years post registration.

Crizotinib in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Removed by Surgery and ALK Fusion Mutations (An ALCHEMIST Treatment Trial)

PRIMARY OBJECTIVES: I. To evaluate whether adjuvant therapy with crizotinib will result in improved overall survival (OS) for patients with stage IB >= 4 cm, II and IIIA, ALK-positive non-small cell lung cancer (NSCLC) following surgical resection. SECONDARY OBJECTIVES: I. To evaluate and compare disease-free survival (DFS) associated with crizotinib. II. To evaluate the safety profile of crizotinib when given in the adjuvant therapy setting. III. To collect tumor tissue and blood specimens for future research. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive crizotinib orally (PO) twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM B: Patients undergo observation. After completion of study treatment, patients are followed up every 6 months if < 4 or 5 years from study entry, and every 12 months if 5-10 or 6-10 years from study entry.