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July 21, 2014
Boehringer Ingelheim released results of a phase II trial of volasertib for older patients with acute myeloid leukemia (AML). The open-
label study enrolled 87 adult patients (median age 75) with AML not considered suitable for intensive induction therapy. Patients were randomly assigned to receive either volasertib in combination with LDAC (n=42) or LDAC (n=45). Patients were randomized in a 1:1 ratio to receive the combination of LDAC plus volasertib 350mg intravenously over one hour on days one and 15 versus LDAC 20mg twice daily subcutaneously on days one to 10 alone. Cycles were scheduled every four weeks until progression, relapse, intolerance or patient/
investigator requested discontinuation. The study’s primary endpoint showed the objective response rate (complete remission or complete remission with incomplete blood count recovery) was more than doubled for patients receiving volasertib and LDAC versus LDAC alone (31% v. 13.3%, p=0.052). The trial showed patients treated with volasertib combined with LDAC had a median overall survival of eight months versus 5.2 months in patients treated with LDAC (p=0.047). Median event-free survival was prolonged in patients receiving volasertib and LDAC versus LDAC (5.6 months v. 2.3 months; p=0.021). Relapse-
free survival for volasertib and LDAC versus LDAC was 18.5 months versus 10 months. There is an ongoing phase III study initiated for volasertib.
June 23, 2014
Ambit Biosciences released results of a
phase II study of quizartinib (AC220) for
FLT3-ITD (+) relapsed or refractory acute
myeloid leukemia. A total of 76 subjects
were enrolled. Dosing was 30mg/day and
60mg/day. The CRc rate remained at 47%
(5% CR+CRp, 42% CRi). The rate of hematopoietic
stem cell transplantation (HSCT)
after quizartinib use remained at 34%. The
median overall survival was 20.9 weeks for
patients initially treated at 30mg/day and
25.4 weeks for patients at 60mg/day, with
24/38 patients censored as they remained
alive in follow-up at the time of the analysis.
In addition, the further follow-up now
shows 24 subjects were alive at >24 weeks
with four subjects alive >12 months. Overall,
the additional follow up continued to show
that both the 30mg and the 60mg doses of
quizartinib showed substantial activity in
terms of overall CRc rate and bridge to HSCT
with impact on improved median OS. The
safety profile is similar at both doses and
QTcF prolongation did not worsen with additional
duration of treatment and/or follow
up. There is a currently ongoing phase III
study of quizartinib (AC220).
June 16, 2014
AbbVie issued results of phase Ib trials of
ABT-199/GDC-0199 in combination with
rituximab for relapsed/refractory chronic
lymphocytic leukemia (CLL) and various
subtypes of non-Hodgkin’s lymphoma
(NHL). The phase I, open-label, multicenter,
international trial of ABT-199/GDC-0199 in
patients with relapsed/refractory CLL and
NHL enrolled 78 patients in the CLL arm and
62 patients in the NHL arm of the trial. In the
CLL arm, due to concerns of TLS, the initial
dose was reduced from 50mg to 20mg and
daily dosing was modified to a weekly rampup
period to the final dose of 400mg. A
ramp-up period with weekly dose increases
occurred from 20mg, 50mg, 100mg, 200mg
to the final recommended phase II dose
(RPTD) of 400mg. The overall response rate
(ORR) was 77%, with 23% achieving complete
response (CR). Of the 18 CR/CRi patients
(complete response with incomplete
blood count recovery), 11 were evaluated
for minimal residual disease (MRD) and six
were found to be MRD negative. The ORR for
patients with 17p deletion and F-refractory
CLL was 79% and 76%, respectively. ABT-
199/GDC-0199 as a monotherapy in patients
with relapsed/refractory CLL harboring the
17p deletion is under investigation in an
ongoing phase II clinical trial.
January 6, 2014
Janssen reported results of a phase Ib/II open-label, multi-center study of ibrutinib for the treatment of previously untreated chronic lymphocytic leukemia (CLL, N=29) or small lymphocytic lymphoma (SLL, N=2) in patients over age 65, assessing oral, once-daily ibrutinib 420mg (27 patients) or 840mg (4 patients). Progression-free survival (PFS) and overall survival (OS) rates at 24 months (based on Kaplan-Meier projections) were estimated to be 96.3% (95% CI, 76.5-99.5) and 96.6% (95% CI, 77.9-99.5) respectively. Efficacy data collected showed 71% (95% CI, 52.0-85.8) of patients treated with ibrutinib achieved an objective response (defined as a complete or partial response). Although estimates of PFS and OS were not reached at the median follow up of 22.1 months, it is estimated that more than 95% of patients would be alive and progression-free at two years. The median time to initial response was 1.9 months (IQR,1.5-7.4 months), while the median time to best response and complete response were 5.9 months (IQR,1.8-22.1 months) and 12 months (IQR, 7.1-15.6 months). Ibrutinib has been submitted to the EMA for the treatment of adult patients with relapsed or refractory CLL/SLL or adult patients with relapsed or refractory MCL.
April 15, 2013
Pharmacyclics reported results from a phase II trial of ibrutinib for relapsed and refractory chronic lymphocytic leukemia (CLL). This study enrolled 53 subjects with CLL, 24 who were treatment naïve and 29 who had a deletion of chromosome 17p. Subjects received ibrutinib for six months. Results showed ibrutinib demonstrated rapid and sustained disease control in blood, lymph nodes, spleen and bone marrow. After six months, 95% of patients experienced a reduction in lymph node size and all showed reduction in spleen enlargement, with a median reduction of 55%. In 26 patients, for whom a bone marrow biopsy was done, tumor infiltration decreased by 82%. The Progression Free Survival probability for these patients at 12 months was estimated to be 94%. Ibrutinib was well tolerated. The most frequent adverse events were diarrhea, fatigue and rash. Based on this data, the FDA has designated ibrutinib as a Breakthrough Therapy in CLL patients with deletion 17p.
December 17, 2012
Boehringer Ingelheim issued preliminary results from a phase II trial of volasertib for the treatment of acute myeloid leukemia (AML). This open-label study enrolled 87 patients with newly-diagnosed AML who were considered ineligible for intensive remission induction therapy. Subjects received volasertib in combination with low-dose cytarabine (LDAC) (n=42) or LDAC alone (n=45). Results showed objective responses were observed in 31% of patients (13/42) treated with the combination of volasertib plus LDAC compared with 13.3% of the patients (6/45) treated with LDAC alone (odds ratio: 2.91; p=0.0523). The median time to remission was 71 (29158) days and 64 (30125) days, respectively. Data also showed that in patients treated with the combination of volasertib plus LDAC, the median event free survival was approximately 5.6 months (170 days) compared with approximately 2.3 months (69 days) in patients treated with LDAC alone (hazard ratio: 0.56; 95% CI: 0.34, 0.93; p=0.0237). Volasertib was well tolerated. The most frequent adverse events were gastrointestinal events, general events, infections, febrile neutropenia, metabolism/nutrition events and respiratory/thoracic/mediastinal events. Based on these data, Boehringer Ingelheim intends to begin recruitment of a phase III study of volasertib in combination with LDAC compared with LDAC alone in early 2013.
December 10, 2012
ARIAD Pharmaceuticals released results from a phase I trial of ponatinib for the treatment of resistant and refractory chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). This dose-escalation study enrolled 81 patients with resistant hematologic cancers, including 60 patients with CML and five patients with Ph+ ALL, who had become resistant to one or more tyrosine kinase inhibitors. Results showed that after 73 weeks, 72% of patients (31 of 43) with chronic-phase CML had a major cytogenetic response (MCyR), including 92% (11 of 12) who had the T315I gatekeeper mutation, the most common mutation among resistant patients. In addition, of 22 patients with accelerated-phase or blast-phase CML or Ph+ ALL, 36% (8 of 22) had a major hematologic response and 32% (7 of 22) had aMCyR. The drug was well tolerated. The most frequent adverse events were rash, thrombocytopenia, arthralgia, increased lipase, fatigue, acneiform dermatitis dry skin and nausea. ARIAD did not disclose its plans for ponatinib.
May 28, 2012
Amgen reported results from a phase II trial of blinatumomab for the treatment of relapsed or refractory B-precursor acute lymphoblastic leukemia. This single-arm, dose-ranging study enrolled 36 subjects who had relapsed following treatment with standard front-line chemotherapy or allogeneic stem cell transplant. Subjects received a continuous intravenous infusion of blinatumomab at an initial dose of five or 15 micrograms per meter squared per day, ranging up to 30 micrograms for the remainder of the treatment for 28 days. The dosing period was followed by two weeks off therapy, and the process then repeated up to four more times. The trial achieved a high-rate of complete response or partial hematologic recovery in 26 (72%) of subjects. At the time of the analysis, median survival was 9.0 (8.2, 15.8) months with a median follow-up period of 10.7 months. In subjects who received the selected dose, median survival was 8.5 months. The drug was generally well tolerated. The most common adverse events were pyrexia, headache, tremor and fatigue. Amgen did not comment on future plans for blinatumomab.
June 21, 2010
Micromet issued positive results from a phase II trial of blinatumomab for minimal residual disease (MRD) positive acute lymphoblastic leukemia (ALL). This trial enrolled 21 subjects who had sub-microscopic evidence of leukemic cells in the bone marrow following treatment with front-line chemotherapy (minimal residual disease). The subjects received 15 micrograms per meter squared per day of blinatumomab for 28 days followed by two weeks off therapy over a six week treatment cycle. The primary endpoint was MRD response. Of 20 evaluable patients, 80% achieved a complete MRD response. Among 13 non-transplanted patients, there were eight with non-Ph+ or t(4;11) disease. For these eight subjects the median time to hematological relapse has not been reached at a median follow-up of 480 days. Six of nine evaluable, MRD responding, non-transplanted patients were in hematologic remission, ranging up to 23 months. Eight of the subjects received an allogeneic transplant after blinatumomab treatment, all of whom are alive and in remission, ranging up to 21 months. Overall, blinatumomab was well-tolerated.
January 15, 2007
Kosan issued positive preliminary results from a phase II trial of tanespimycin plus Herceptin for the treatment of Herceptin-refractory HER2-positive metastatic breast cancer. This trial was designed to determine the objective response rate according to RECIST criteria in subjects with HER2-positive metastatic breast cancer with tumor progression during treatment with one Herceptin-containing regimen immediately prior to entering the trial. The trial enrolled 12 subjects who received tanespimycin (450 mg/m2) via a two-hour weekly intravenous infusion administered along with the standard dose of Herceptin. Treatment was well tolerated, with adverse events mild in nature. Of the eight subjects evaluable for efficacy, five (63%) showed signs of clinical benefit and three who had received 4-6+ cycles of treatment had stable disease. Based on the results Kosan plans to advance the development of tanespimycin into phase III trials.
Vertex and Merck announced positive results from a phase I trial of VX-680 (MK-0457) for the treatment of resistant leukemias and myeloproliferative diseases. This trial enrolled 44 subjects with chronic myelogenous leukemia (CML), Philadelphia chromosome-positive acute lymphocytic leukemia (Ph+ ALL), or myeloproliferative diseases (MPD). Subjects were treated with VX-680 given as a five-day intravenous infusion every two-to-three weeks. No treatment related toxicities were reported and thus the maximum tolerated dose was not yet determined. Out of the 15 subjects with CML, nine had a T315I BCR-ABL mutation. Eight of these nine T315I subjects had either a hematologic and/or cytogenetic response to VX-680 following multiple cycles of treatment. The six subjects without the T315I BCR-ABL mutation did not exhibit any clinical responses. In addition, two subjects in the study with Ph+ ALL carrying the T315I mutation had either hematologic and/or cytogenetic responses, including one who had a clinical response with a full molecular remission. Six of the nine subjects with MPD having the V617F activating mutation in JAK-2 also had clinical responses. Based on these results, a phase II trial is planned for January of 2007.
December 4, 2006
Cyclacel released positive interim results from a phase I trial of sapacitabine for the treatment of advanced leukemia or myelodysplastic syndromes (MDS). The preliminary data is from 22 subjects. The primary endpoint of this trial was to determine the maximum tolerated dose (MTD) of sapacitabine administered twice daily by mouth for seven consecutive days, every 21 days. One subject receiving a dose level of 275 mg b.i.d. experienced a dose limiting toxicity, which was resolved after treatment ceased. Dose escalation was ongoing at this time with dose limiting toxicities not yet reached at the dose level of 325 mg b.i.d. Cyclacel planned to use these results in the design of a phase II trial expected to commence in 2007.
September 5, 2006
SGX Pharmaceuticals announced negative results from a phase II/III trial of Troxatyl as a third-line treatment for acute myelogenous leukemia (AML). This trial enrolled 211 subjects in the US and Europe. The trial was designed to demonstrate an improvement over the historical data from the M.D. Anderson Cancer Center database, which documented a complete response rate of 4.7% in this patient subgroup. The observed response rates in the Phase II/III trial to date did not show a meaningful improvement over the response rates in the M.D. Anderson Cancer Center historical database. Based on this, a Data Safety Monitoring Board recommended that the trial be discontinued due to lack of evidence that Troxatyl would provide treatment benefit as a third-line treatment for AML. SGX planned to analyze data further in order to determine a future course of action.
April 10, 2006
ArQule issued positive results of a phase I trial of ARQ 501, for the treatment of solid tumors, at the AACR Annual Meeting. Results from the study yielded preliminary efficacy, with tumor regression (2 parital responses, 3 minor responses) or disease stabilization (13 subjects) observed in a number of cancer types, including pancreatic, head and neck, ovarian, and colorectal cancers and leiomyosarcoma. Safety data were also generally positive: serious adverse events included hyperbilirubinemia and dose-limiting hemolytic anemia, but these were transient and clinically manageable. This open-label study enrolled a total of 64 subjects, who received dose-ranging regimens of the drug (10 mg/m2 to 660 mg/m2) via one- or three-hour infusion.
Maxim, through their merger partner EpiCept, announced positive results of a phase III trial of Ceplene for the treatment of AML in the journal Blood. This randomized study enrolled 320 subjects in 11 countries, who received Ceplene plus low dose interleukin-2 or current standard of care (no treatment). Results from the study achieved significance in the primary efficacy endpoint, extending leukemia-free survival at >3 years of follow-up (p=0.0096 in intent-to-treat analysis); the majority of responses were in patients experiencing their first complete remissions (n=261), among whom 3-year leukemia free survival rates were 40% vs. 26% (p=0.01). No treatment-related mortality was observed, and rate of serious adverse events for Ceplene therapy was comparable to the control group.
Sunesis announced positive results of a phase I trial of SNS-595, their napthyridine analog under investigation for the treatment of solid tumors, at the Annual Meeting of the American Association for Cancer Research (AACR). Trial data yielded preliminary evidence of clinical activity, with 28.6% of subjects (n=6/21) achieving sustained disease control through at least 16 weeks; one partial tumor response was noted at the maximum tolerated dose. The drug was shown to be well tolerated: one case of dose-limiting neutropenia was observed, while other adverse events were generally mild. This open-label dose-escalation study enrolled 21 patients with advanced solid tumors. These data were seen to support ongoing phase I (acute leukemias) and phase II (non-small cell and small cell lung cancers) trials of the drug.
January 23, 2006
Breakthrough Therapeutics issued positive interim results of a clinical trial of CMLVAX100, for the treatment of chronic myeloid leukemia (CML). Results of the study indicated that the vaccine was immunogenic in 94% (n=17/18) subjects, producing peptide specific T-cell response. 6 of 10 patients who presented cytogenetic evidence of CML on enrollment experienced complete cytogenic response, and 3 achieved undetectable levels of disease biomarker (bcr-abl transcript). Adverse events were limited to injection-site reactions. This open-label study enrolled 21 patients with stable residual disease following treatment with imatinib, who received 6 vaccinations 2 weeks apart, with additional doses every 4-6 months for positive responders.
GTx has reported positive interim results of a pair of phase III trials of Acapodene (toremifene citrate), for the prevention of prostate cancer, and for the treatment of adverse events associated with androgen deprivation therapy (ADT) for prostate cancer. Preliminary safety data from the fist study were sufficiently positive for the trial's drug safety monitoring board (DSMB) to recommend that the study continue unchanged. Initial results from the second study yielded significant improvements in bone mineral density in the lumbar spine (+2.3%; p<0.001), the hip (+2.0%; p=0.001), and the femur (+1.5%; p=0.009) , vs. placebo. Continuation of the second study was also recommended by its DSMB. The first study enrolled 1,260 men with prostatic intraepithelial neoplasia across 130 sites in the US, Canada, Mexico and Argentina; subjects received 20 mg of the drug or placebo daily. The second study enrolled 1,388 patients on ADT across 150 sites in the US and Mexico, who received 80 mg oral Acapodene or placebo daily.
May 24, 2004
Maxim Pharmaceuticals reported results from a phase III trial investigating Ceplene plus interleukin-2 (IL-2) for the treatment of acute myeloid leukemia (AML). Results showed that subjects treat with Ceplene plus IL-2 experienced a statistically significant increase in leukemia-free survival compared with subjects in the control arm, the studies primary endpoint. The randomized study enrolled 320 subjects with AML in complete remission at multiple sites in North America, Europe, Israel, New Zealand and Australia. Subjects received Ceplene plus IL-2 or the current standard-of-care (no treatment) for at least three years. Significance was assessed by the stratified log-rank test.
April 26, 2004
Bioenvision reported positive interim results from a phase II trial investigating clofarabine, a purine nucleoside analogue for the treatment of with acute myeloid leukemia (AML). Results showed that clofarabine achieved a complete response rate of 64%. The investigator-sponsored study enrolled 18 subjects and was designed to test clofarabine, as first line treatment in older adults with AML considered unsuitable for intensive chemotherapy. Results were reported at the British Society of Hematology meeting in Cardiff, U.K. Clofarabine has demonstrated efficacy in children with relapsed/refractory acute leukemias and in adults with relapsed/refractory AML. Bioenvision plans to begin a European regulatory trial with clofarabine in the same patient population.
August 4, 2003
SuperGen reported positive results from a phase II trial investigating Dacogen (decitabine), a DNA methyltransferase inhibitor for the treatment of chronic myelogenous leukemia. Results showed that 55 subjects achieved an overall objective response, a rate of 43%. There was no significant difference in the response rates among dose levels in the accelerated and blastic phase subjects. Objective response was defined as a complete hematological response, partial hematological response, hematological improvement or a return to the second chronic phase. The study enrolled 130 subjects, most of which were in the blastic or accelerated phase of the disease. Results were published in the August issue of the journal Cancer.
July 14, 2003
EntreMed reported positive results from a phase I trial investigating Panzem (2-Methoxyestradiol (2ME2)), an endogenous estrogen metabolite for the treatment of ovarian cancer. Results showed the drug produced an objective response in one subject with ovarian cancer. The subject demonstrated a 67% reduction in tumor volume and a 78% reduction in the CA125 marker. A maximum tolerated dose was not reached and minimum side effects were reported. The randomized, dose-escalating study enrolled 17 subjects with advanced solid tumors who had an average of six other therapies. The study was conducted by the National Cancer Institute in Bethesda, Maryland. Results were presented at the American Society of Clinical Oncology Annual Meeting in Chicago.<
ILEX Oncology reported positive results from a phase III trial investigating Campath (alemtuzumab), an approved drug, for the first line therapy in subjects with chronic lymphocytic leukemia. Results demonstrated a trend toward longer progression-free survival in subjects taking Campath. Data showed that six subjects achieved molecular remission, which is linked to progression-free survival. The randomized, dose escalating, controlled study enrolled 23 subject who were in remission following first-line therapy with Fludarabine or Fludarabine plus cyclophosphamide. Results were presented at the 2003 Annual Meeting of the American Society of Clinical Oncology.
April 7, 2003
SuperGen reported positive results from a phase II trial investigating Nipent (pentostatin), an injectable antimetabolite for the treatment of chronic lymphocytic leukemia. Results showed there were 17 responses (4 complete and 13 partial) out of 23 subjects for an overall response rate of 74 %. The overall median response duration was 7 months. Subjects achieving complete responses had a median response of 13 months and partial response had a median response of 6 months. Treatment well tolerated with the most common adverse effects reported as mild fatigue and nausea. Serious adverse events included neutropenia, thrombocytopenia and infection. Subjects received six treatment cycles consisting of Nipent and one of two dose levels of cyclophosphamide. The study enrolled 23 subjects with previously treated CLL and was designed to test the efficacy of Nipent in combination with cyclophphamide.
January 27, 2003
Amgen reported positive results from a phase III trial investigating rHu-KGF, a natural keratinocyte growth factor for the treatment of oral mucositis as a complication of cancer treatments. Preliminary results from the randomized, double blind trial were positive on all endpoints showing a highly significant decrease in both the duration and incidence of severe mucositis. In addition, results showed that the drug was well tolerated. The study enrolled subjects who underwent bone marrow transplantation treatment for hematologic malignancies such as lymphoma, multiple myeloma, and leukemia.
December 16, 2002
SuperGen reported positive results from more than 12 trials investigating Nipent for the treatment of multiple cancers. A phase II trial using Nipent in combination with Rituximab for the treatment of chronic lymphocytic leukemia (CLL) demonstrated that 33% of subjects achieved an objective response. Stable disease was observed in 54% of subjects with a median response of 9.8 months. A phase I trial using Nipent for the treatment of steroid refractory acute graft-versus-host disease enrolled 23 subjects with a variety of hematological malignancies. Results showed 11 subjects achieved complete responses and 6 achieved partial or mixed responses. A long term follow-up study of Nipent in 180 subjects with hairy cell leukemia demonstrated a response rate of 98%. Data showed that 83% of subjects achieved a complete response and 15% achieved a partial response.
December 9, 2002
Advanced Magnetics and Cytogen reported positive results from a phase III trial investigating Combidex, an investigational contrast agent for use with magnetic resonance imaging (MRI). The study showed that Combidex is able to distinguish malignant lymph nodes from normal ones in a variety of cancers. In one part of the study, 50 subjects with primary prostate cancer who were scheduled for radical prostatectomy were given an MRI. Using Combidex, the analysis detected malignant lymph nodes with 93% specificity and 92% sensitivity, indicating a high level of correlation. In another part of the study, 12 subjects with renal cancer who were scheduled for radical nephrectomy were given an MRI. Using Combidex, the analysis detected malignant lymph nodes with 86.6% sensitivity and 96.9% specificity, resulting in a positive predictive value of 76.4% and a negative predictive value of 98.4%. Lymph node status is essential for determining the most appropriate strategy in cancer treatment.
Vasogen reported positive results from a phase II trial investigating their immune modulation therapy, an inflammation suppressor for the treatment of chronic lymphocytic leukemia. More than 60% of the treatment subjects in the optimal dose group reached the primary end-point, which was a 25% reduction in total tumor burden or a greater than 25% reduction in lymph node size compared to baseline. The open-label pilot study enrolled 18 subjects with chronic lymphocytic leukemia who were treated in three groups of six subjects each. The study showed the therapy was well tolerated with no treatment related adverse events.
December 2, 2002
Cell Therapeutics reported positive results from a series of clinical trials investigating Trisenox (arsenic trioxide) and concluded that the drug may be effective in inducing high rates of remission in hematologic malignancies like myelodysplasia (MDS) and chronic myeloid leukemia (CML). In the study, 29 subjects with newly diagnosed CML, 19 subjects (66 %) achieved complete remission with four subjects achieving partial remission for an overall response rate of 79 %. In 21 subjects with MDS-refractory anemia (MDS-RA), six subjects (29 %) achieved a complete remission and eight subjects (38 %) achieved a partial remission for an overall objective response rate of 67 %. In 18 subjects with MDS-refractory anemia with excess blasts (MDS-RAEB), three achieved stable disease or better.
Kosan Biosciences and Roche reported positive interim results from a phase I trial investigating KOS-862 (Epothilone D), a polyketide natural product similar to paclitaxel for the treatment of advanced solid tumors. The study is determining possible drug-related toxicities, pharmacokinetics, and pharmacodynamics of escalating intravenous doses of KOS-862 administered every 3 weeks. Pharmacokinetics are linear and the drug shows a 10-hour half-life with good tissue penetration. The pharmacodynamic measurements demonstrate that maximal microtubule bundle formation in peripheral blood cells correlates with maximal plasma concentrations. To date, KOS-862 has been evaluated in 42 subjects with results showing no myelosuppression.