Clinical trial NCT02013167
Conditions: Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia
Keywords: Relapsed; Refractory; B-precursor; Acute Lymphoblastic Leukemia; Philadelphia Negative; ALL; Blinatumomab; Leukemia; Standard of Care; SOC
Sponsor: Amgen
Start date: 2014-01-03; Completion date: 2017-03-14
Enrollment: 405 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective was to evaluate the effect of blinatumomab on overall survival when compared to standard of care (SOC) chemotherapy.

Detailed description:
Adults with relapsed/refractory B-cell precursor ALL were randomized in a 2:1 ratio to receive blinatumomab or 1 of 4 pre-specified, investigator-chosen, SOC chemotherapy regimens. Randomization was stratified by age (\< 35 years vs ≥ 35 years of age), prior salvage therapy (yes vs no), and prior allogeneic HSCT (yes vs no) as assessed at the time of consent.

The study consisted of up to a 3-week screening and pre-phase period, a treatment period consisting of induction with 2 cycles of either blinatumomab or SOC chemotherapy, a consolidation phase of up to 3 additional cycles of protocol-specified therapy, and a maintenance phase for up to an additional 12 months with protocol-specified therapy. A safety follow-up visit 30 days after the last dose of protocol-specified therapy and a long-term follow-up period were included. The long-term follow-up part of the study was discontinued prematurely based on a recommendation from the data monitoring committee (DMC) that the study be stopped for benefit.

Arms: arm 1: Participants received blinatumomab by continuous intravenous infusion (CIVI) over 4 weeks followed by a 2 week treatment-free interval for 2 induction cycles. Participants who achieved a bone marrow response, complete remission, or complete remission with partial or incomplete hematologic recovery (CR/CRh\*/CRi) within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh\*/CRi could continue to receive blinatumomab for an additional 12 months (4 cycles), where 1 cycle consisted of 4 weeks of CIVI followed by an 8-week treatment-free period.

The initial dose of blinatumomab was 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 through day 29 and for all subsequent cycles. arm 2: Participants received one of four prespecified, investigator-chosen chemotherapy regimens for 2 induction cycles. Participants who achieved a bone marrow response, CR/CRh\*/CRi within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of SOC chemotherapy.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh\*/CRi could continue to receive SOC therapy for an additional 12 months.
Interventions: intervention 1: Blinatumomab intervention 2: Standard of Care Chemotherapy
Intervention descriptions: intervention 1: Blinatumomab is administered as a continuous intravenous infusion (CIV). intervention 2: * FLAG (fludarabine, cytarabine arabinoside, and granulocyte colony-stimulating factor) ± anthracycline-based regimen (e.g. idarubicin 10 mg/m² days 1 \& 3; fludarabine 30 mg/m² days 1-5; cytarabine arabinoside 2 g/m² days 1-5). Patients \> 60 years: Idarubicin 5 mg/m² day 1 \& 3; fludarabine 20 mg/m² day 1-5; cytarabine arabinoside 1 g/m² day 1-5
* HiDAC (high-dose cytarabine arabinoside) - based regimen ≥1 g/m²/day ± anthracycline and/or in combination with other drugs such as native Escherichia coli asparaginase, polyethylene glycol linked to asparaginase (PEG-asparaginase), vinca alkaloids, steroids, etoposide or alkylating agents
* High-dose methotrexate-based regimen (HDMTX; 500 mg/m² to 3 g/m² infused up to 24 hours) in combination with native E. coli asparaginase, PEG-asparaginase, vinca alkaloids, steroids, etoposide or alkylating agents.
* Clofarabine as a single agent as recommended in the prescribing information or clofarabine-based regimens with 20 mg/m²/day for up to 5 days.

Protocol documents: