Leukemia (Pediatric)

December 18, 2017

Verastem announced results from the phase III DUO study evaluating the efficacy and safety of duvelisib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). In the study, 319 patients were randomized 1:1 to receive either duvelisib 25mg orally twice daily or ofatumumab monotherapy, an approved standard of care treatment for use in CLL/SLL, per its label with an initial infusion of 300 mg followed by seven weekly infusions and four monthly infusions of 2,000mg. The DUO study met its primary endpoint with oral duvelisib monotherapy achieving a statistically significant improvement in median PFS (mPFS) compared to ofatumumab in patients with relapsed or refractory CLL/ SLL per a blinded Independent Review Committee (IRC) using iwCLL or revised IWG Response Criteria (modified iwCLL/ IWG; 13.3 months vs 9.9 months, respectively; HR=0.52; p<0.0001), representing a 48% reduction in the risk of progression or death. Similar efficacy of duvelisib was observed regardless of whether patients had 17p deletion (del[17p]). The primary outcome of mPFS via IRC review in the del[17p] subpopulation significantly favored duvelisib over ofatumumab (12.7 months vs 9.0 months, respectively; HR=0.41; p=0.0011), representing a 59% reduction in the risk of progression or death. Per investigator assessment, duvelisib demonstrated a mPFS of 17.6 months, compared to 9.7 months for ofatumumab (HR=0.40, p<0.0001). Duvelisib maintained a PFS advantage in all patient subgroups analyzed as a subset of pre-specified sensitivity analyses. Verastem plans to submit a NDA to the FDA requesting full approval of duvelisib for the treatment of patients with relapsed or refractory CLL/SLL, and accelerated approval for the treatment of patients with relapsed or refractory FL. The company expects to submit the duvelisib NDA during the first quarter of 2018.

April 11, 2016

BioLineRx issued results from BL-8040’s phase II trial in relapsed or refractory acute myeloid leukemia (r/r AML). The trial was a multicenter, open-label study assessing pharmacodynamics and pharmacokinetic parameters of BL-8040 in combination with Cytarabine (Ara-C). Forty-two patients with r/r AML were enrolled in the study (36 of which received a dose of 1mg/kg and higher). The study included a dose escalation stage followed by an expansion stage. Each patient received a once daily dose of BL-8040 monotherapy (from 0.5 to 2mg/kg) on days one to two, followed by the same dose of BL-8040 plus Ara-C on days three to seven. Extensive pharmacodynamic parameters, such as mobilization of leukemic cells and induction of apoptosis, were assessed after monotherapy with BL-8040 using peripheral blood sampling and bone marrow aspirates at baseline and on day three prior to Ara-C administration. Clinical response to treatment was evaluated by bone marrow biopsy on day 30. Results showed BL-8040, as a single agent and in combination with Cytarabine (Ara-C), was safe and well-tolerated at all doses tested up to and including the highest dose level of 2mg/kg, with no major adverse events (n=45). The composite complete remission rate, including both complete remission (CR) and complete remission with incomplete blood count recovery (CRi), was 38% in subjects receiving up to two cycles of BL-8040 treatment at doses of 1mg/kg and higher (n=39). The company plans multiple additional clinical studies for BL-8040. An AML consolidation treatment is currently being investigated in a large phase IIb study at in Germany.  

April 4, 2016

Celator Pharmaceuticals reported results of a phase III trial of VYXEOS (cytarabine: daunorubicin) Liposome Injection (also known as CPX-351) in patients with high-risk (secondary) acute myeloid leukemia (AML) compared to the standard of care regimen of cytarabine and daunorubicin known as 7+3. The median overall survival for patients treated with VYXEOS in the study was 9.56 months compared to 5.95 months for patients receiving 7+3, representing a 3.61 month improvement in favor of VYXEOS. The hazard ratio (HR) was 0.69 (p=0.005) which represents a 31% reduction in the risk of death versus 7+3. The percentage of patients alive 12 months after randomization was 41.5% on the VYXEOS arm compared to 27.6% on the 7+3 arm. The percentage of patients alive 24 months after randomization was 31.1% on the VYXEOS arm compared to 12.3% on the 7+3 arm. VYXEOS also demonstrated a statistically significant improvement in induction response rate (CR+CRi of 47.7% v. 33.3%; p=0.016) and this significance was maintained for the analysis of CR alone (CR of 37.3% v. 25.6%, p=0.040). Sixty-day all-cause mortality was 13.7% v. 21.2%, in favor of patients treated with VYXEOS. Based on these results the company expects to submit an NDA for VYXEOS with the FDA later this year and submit an MAA with the EMA in the first quarter of 2017. No substantial difference in Grade 3 or higher adverse events was observed between VYXEOS and 7+3. In the intent-to-treat population, Grade 3 or higher, hematologic adverse events were similar for overall infections, febrile neutropenia, and bleeding events. In the intent-to-treat population, Grade 3 or higher, non-hematologic adverse events were similar across all organ systems, including cardiac, gastrointestinal, general systems, metabolic disorders, musculoskeletal, nervous system, respiratory, skin and renal.

November 3, 2014

Novartis and the University of Pennsylvania’s Perelman School of Medicine reported results of two pilot trials evaluating CTL019 in patients with relapsed/refractory acute lymphoblastic leukemia (r/r ALL). Twenty-five patients enrolled in the pediatric pilot trial and five patients enrolled in the adult pilot trial. The study found 27 of 30 pediatric and adult patients with r/r ALL (90%) experienced complete remissions, including two blinatumomab-refractory patients and 15 with prior stem cell transplant. Of the 27 patients who achieved a complete remission, five went off-study for alternate therapy, three of whom proceeded to allogeneic SCT in remission. Fifteen patients remain in remission with a median follow-up of seven months. Sustained remissions were achieved up to two years with six-month, event-free survival 67% (95% CI, 51% to 88%) and overall survival 78% (95% CI, 65% to 95%). The probability of six-month CTL019 persistence was 68% (95% CI, 50 to 92%) and relapse-free B cell aplasia was 73% (95% CI, 57 to 97%). CTL019-modified T cells were detectable in the blood by flow cytometry for up to 11 months, and CTL019 sequences remained detectable by quantitative PCR (Q-PCR) in patients with sustained remissions for up to two years.

October 13, 2014

Erytech reported results of a phase III study of Graspa for acute lymphoblastic leukemia (ALL). The three-arm, controlled, multicenter trial enrolled 80 children and adults. The first two arms compared Graspa to native E. Coli L-asparaginase, both in combination with standard chemotherapy, in a 1-to-1 randomization in patients without prior allergies to L-asparaginase. The third arm was an open-label assessment of Graspa for patients who have experienced allergic reactions related to asparaginase in their first-line treatment. None of the 26 patients in the Graspa arm experienced an allergic reaction v. 12 of the 28 (42.9%) patients treated with reference L-asparaginase in the control group (p<001). In the Graspa group, asparaginase levels were maintained above 100 IU/l for an average of 20.5 days with up to two injections during the first month of treatment (induction phase) v. 9.2 days in the control group with up to eight injections of reference L-asparaginase (p<001). At the end of the induction phase, 15 patients (71.4%) in the Graspa arm show complete remission v. 11 patients (42.3%) in the control arm. Erytech intends to submit an application to the European Marketing Authorization in the first half of 2015.