Overview

This trial is active, not recruiting.

Condition adult subjects with relapsed/refractory b-precursor acute lymphoblastic leukemia
Treatments blinatumomab, standard of care chemotherapy
Phase phase 3
Target CD19
Sponsor Amgen
Start date January 2014
End date December 2015
Trial size 405 participants
Trial identifier NCT02013167, 00103311

Summary

This study seeks adult subjects with Relapsed/Refractory (R/R) B-precursor ALL. This is a phase 3 randomized, open label study designed to evaluate the efficacy of blinatumomab versus investigator choice of SOC chemotherapy. Adult subjects with R/R B-precursor ALL will be randomized in a 2:1 ratio to receive blinatumomab or treatment with investigator choice of 1 of 4 protocol defined SOC chemotherapy regimens. Primary Endpoint is Overall Survival.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Blinatumomab is administered as a continuous intravenous infusion (CIVI). A single cycle of blinatumomab treatment is 6 weeks in duration, which includes 4 weeks of blinatumomab CIVI followed by a 2 week treatment-free interval. In the first induction cycle, the initial dose of blinatumomab will be 9 μg/day for the first 7 days of treatment which then will be escalated (dose step) to 28 μg/day starting on day 8 (week 2) through day 29 (week 4). For all subsequent cycles (beginning with the second induction cycle and continuing through consolidation and maintenance, for applicable subjects) 28 μg/day will be the dose for all 4 weeks of continuous treatment.
blinatumomab
Blinatumomab is administered as a continuous intravenous infusion (CIVI). A single cycle of blinatumomab treatment is 6 weeks in duration, which includes 4 weeks of blinatumomab CIVI followed by a 2 week treatment-free interval. In the first induction cycle, the initial dose of blinatumomab will be 9 μg/day for the first 7 days of treatment which then will be escalated (dose step) to 28 μg/day starting on day 8 (week 2) through day 29 (week 4). For all subsequent cycles (beginning with the second induction cycle and continuing through consolidation and maintenance, for applicable subjects) 28 μg/day will be the dose for all 4 weeks of continuous treatment.
(Active Comparator)
Subjects randomized to receive SOC chemotherapy will be assigned to one of four chemotherapy regimens per investigator´s choice.
standard of care chemotherapy
Drug: FLAG ± anthracycline based regimen (Idarubicin, fludarabine, cytarabine) Dose: Idarubicin 10mg/m2 days 1, 3: cytarabine 2g/m2 IV days 1-5; fludarabine 30 mg/m2 days 1-5 Dose: Subject's age >60: Idarubicin 5 mg/m2 day 1,3; fludarabine 20 mg/m2 days 1-5; cytarabine 1 g/m2 days 1-5 Drug: High dose cytarabine: cytarabine arabinoside ± anthracycline and/or in comb with native E.coli asparaginase, PEG-asparaginase, vinca alkaloids, steroids, etoposide or alkylating agents Dose: Cytarabine arabinoside at least 1 g/m2 or < per day Drug: High-dose methotrexate in combination with native E.coli asparaginase, PEG-asparaginase, vinca alkaloids, steroids, etoposide or alkylating agents Dose: High-dose methotrexate such as 500 mg/m2 - 3 g/m2 HDMTX (infusion time up to 24 hours) Drug: Clofarabine or clofarabine based regimens Dose: Clofarabine use as single agent: recommended prescribing info. Clofarabine combination based regimens should use ≥ 20 mg/m2/day for up to 5 days.

Primary Outcomes

Measure
Overall Survival
time frame: Approximately 3-4 years

Secondary Outcomes

Measure
Number of Participants with CR within 12 weeks of treatment initiation.
time frame: Approximately 12 weeks
Duration of CR
time frame: Approximately 2 years
Duration of CR/CRh*/CRi
time frame: Approximately 2 years
Number of participants with MRD remission (defined as MRD level below 10-4 by PCR or flow cytometry)
time frame: Approximately 2 years
Time to a 10 point decrease from baseline in global health status and QoL scale using EORTC QLQ-C30, or EFS event
time frame: Approximately 2 years
Number of participants with AlloHSCT with or without blinatumomab treatment
time frame: Approximately 2 years
Number of participants with adverse events
time frame: Approximately 2 years
Number of participants reaching 100-day mortality after alloHSCT
time frame: 100 days
Number of participants with anti-blinatumomab antibody formation
time frame: Approximately 2 years
Number of participants with a change in select vital sign and laboratory parameters
time frame: Approximately 2 years
Number of Participants with CR/CRh*/CRi within 12 weeks of treatment initiation.
time frame: Approximately 12 weeks
Number of Participants with event Free Survival (EFS)
time frame: Approximately 12 weeks

Eligibility Criteria

Male or female participants at least 18 years old.

Subjects with Philadelphia negative B-precursor ALL, with any of the following: - refractory to primary induction therapy or refractory to salvage therapy, - in untreated first relapse with first remission duration <12 months - in untreated second or greater relapse - or relapse at any time after allogeneic HSCT - Subject has received intensive combination chemotherapy for the treatment of ALL for initial treatment or subsequent salvage therapy. - Greater than 5% blasts in the bone marrow - Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 - Age ≥ 18 years at the time of informed consent - Subject has provided informed consent or subject's legally acceptable representative has provided informed consent when the subject has any kind of condition that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent.

Additional Information

Official title A Phase 3, Randomized, Open Label Study Investigating the Efficacy of the BiTE Antibody Blinatumomab Versus Standard of Care Chemotherapy in Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL) (TOWER Study)
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Amgen.