Chronic Myeloid Leukemia

July 4, 2016

Celator Pharmaceuticals issued results of a phase III trial of VYXEOS (cytarabine: daunorubicin) Liposome for Injection (CPX-351) in patients with high-risk acute myeloid leukemia (AML). The randomized, controlled trial enrolled 309 patients, and compared VYXEOS to the conventional cytarabine and daunorubicin treatment regimen (commonly referred to as 7+3) as first-line therapy in older (60-75 years of age) patients. Patients were randomized 1:1 to receive either VYXEOS or 7+3. First induction for VYXEOS was 100u/m2; days one, three and five by 90-minute infusion, and for the control arm was cytarabine 100mg/m2/day by continuous infusion for seven days and daunorubicin 60mg/m2 on days one, two and three (7+3). Second induction for VYXEOS-treated patients was 100u/m2 on days one and three, and the control arm was cytarabine 100mg/ m2/day by continuous infusion for five days and daunorubicin 60mg/m2 on days one and two (5+2). An improvement in overall survival was also observed in FLT3 mutated patients with median overall survival of 10.25 months in the VYXEOS arm compared to 4.55 months in the 7+3 arm. The Hazard Ratio (HR) was 0.57 (p=0.093). In addition, preliminary data on NPM1 and CEBP mutations were presented showing an improvement in response rate and overall survival in patients with these mutations. The company expects to submit a NDA for VYXEOS with the FDA by the end of the third quarter of 2016.

August 10, 2015

Sunesis Pharmaceuticals issued results of a phase III trial of vosaroxin and cytarabine in 711 patients with relapsed or refractory acute myeloid leukemia (AML). VALOR is a randomized, double-blind, placebo-controlled trial conducted at 124 sites in 15 countries. Patients were stratified for age, geographic region and disease status and randomized one-to-one to receive either vosaroxin and cytarabine or placebo and cytarabine. Although no significant difference was observed in the primary endpoint of overall survival (OS) between groups (unstratified analysis, median 7.5 months for vosaroxin and cytarabine [vos/cyt] v. 6.1 months for placebo and cytarabine [pla/cyt], HR=0.87, p=0.061), OS was significantly prolonged in a predefined analysis that stratified by factors used in randomization (stratified log-rank p=0.024). This was supported by a sensitivity analysis of OS censoring for subsequent transplant (median 6.7 months [vos/cyt] v. 5.3 months [pla/cyt], HR=0.81, p=0.024). Prespecified subgroup analyses according to randomization strata demonstrated that OS benefit with vosaroxin was greatest in patients age =60 years (7.1 months [vos/cyt] v. 5 months [pla/cyt], HR=0.75; p=0.0030). Median OS was not significantly different between treatment arms in patients age <60 years (HR=1.08; p=0.60). The complete remission (CR) rate, the sole secondary efficacy endpoint in the VALOR trial, was significantly greater with vosaroxin (30.1% v. 16.3% with pla/ cyt, p<0.0001). Combined complete remission rate was 37.1% and 18.6% for the vos/cyt and pla/cyt treatment arms, respectively (p<0.0001). Prespecified subgroup analyses demonstrated significantly higher response rates for vos/cyt-treated patients across all randomization strata except for those less than 60 years of age, with the most pronounced improvement in patients aged =60 years (CR: 31.9% for vos/cyt vs 13.8% for pla/cyt; p<0.0001). A higher proportion of patients in the vos/cyt arm achieved CR with study drug prior to transplant (48% vos/ cyt; 32% pla/cyt). In patients with CR, median leukemia-free survival (LFS) was 11 months with vos/cyt v. 8.7 months with pla/cyt (HR=0.89; p=0.63). Event-free survival (EFS) was significantly prolonged in vos/cyt-treated patients (HR=0.67; p<0.0001). Thirty-day and 60-day all-cause mortality was similar in the two treatment arms (30-day: 7.9% v. 6.6%; 60-day: 19.7% v. 19.4% for vos/cyt vs pla/cyt, respectively). The company is proceeding with registration in Europe and the U.S.

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.

July 28, 2008

Antisoma issued positive interim results from a phase II trial of AS1411 for the treatment of Acute Myeloid Leukemia (AML). This trial planned to enroll 70 subjects with relapsed or refractory AML, in the United States. The trial was designed to evaluate the addition of low dose and high dose AS1411 to cytarabine (current standard of care) to cytarabine alone. Reported data is from 33 subjects who were enrolled in the low dose stage of the trial. These subjects were randomized to receive either 10 mg/kg/day AS1411 plus cytarabine or cytarabine alone. Treatment was well tolerated at this dose. Among 11 subjects who received AS1411 plus cytarabine, one had a complete response (CR) and one had a complete response with incomplete recovery of platelet counts (CRP); a third subject had a cytogenetic response but had leukemic blasts remaining. Among five subjects who received cytarabine alone, none had a CR, none had a CRP and there were no cytogenetic responses. The subjects who did not respond to cytarabine alone were allowed to cross over to receive AS1411 plus cytarabine. Two of the first five subjects crossed over, one of whom showed a 90% reduction in leukemic blast count after treatment with the combination. Enrollment is currently underway in the high dose stage of the trial, comparing 40 mg/kg/day AS1411 plus cytarabine with cytarabine alone.

January 14, 2002

Phase II trial results indicate that rubitecan, an oral anticancer drug, is active in both chronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS). The trial included 35 evaluable subjects who had received a minimum of one prior therapy and who were diagnosed with either CMML (23 subjects) or MDS (12 subjects). Results showed an objective response rate of 28%, with four complete responses and six partial responses. An overall response rate of 42% was reported, taking into account hematological improvement in 14% of subjects. Rubitecan is being developed by SuperGen.

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