NCT02393859|CompletedPhase 3ResultsDMC

Phase 3 Trial of Blinatumomab vs Standard Chemotherapy in Pediatric Subjects With HIgh-Risk (HR) First Relapse B-precursor Acute Lymphoblastic Leukemia (ALL)

Phase 3 Trial to Investigate the Efficacy, Safety, and Tolerability of Blinatumomab as Consolidation Therapy Versus Conventional Consolidation Chemotherapy in Pediatric Subjects With HR First Relapse B-precursor ALL

Amgen ClinicalTrials.gov

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2 other identifiers

201202152014-002476-92

Study Type

interventional

Target

111

Locations

23 countries

Sites

Timeline

RegisteredMar 2015

StartedNov 2015

CompletionNov 2022

Brief Summary

B-precursor ALL is an aggressive malignant disease. Therapy is usually stratified according to risk characteristics to ensure that appropriate treatment is administered to patients with high-risk of relapse. In general, pediatric treatment regimens are more intense than those employed in adults and include courses of combination chemotherapy. Standard of care chemotherapy is associated with considerable toxicity. There is a lack of novel treatment options for subjects who relapse or are refractory to treatment. Therefore, innovative therapeutic approaches are urgently needed. Blinatumomab is a bispecific single-chain antibody construct designed to link B cells and T cells resulting in T cell activation and a cytotoxic T cell response against CD19 expressing cells. This study will evaluate the event-free survival (EFS) after treatment with blinatumomab when compared to standard of care (SOC) chemotherapy. The effect of blinatumomab on overall survival and reduction of minimal residual disease compared to SOC chemotherapy will also be investigated.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

111

participants targeted

Target at P25-P50 for phase_3

Timeline

Completed

Started Nov 2015

Longer than P75 for phase_3

Geographic Reach

23 countries

99 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

7 years study duration

First Submitted

Initial submission to the registry

March 16, 2015

Completed

4 days until next milestone

First Posted

Study publicly available on registry

March 20, 2015

Completed

8 months until next milestone

Study Start

First participant enrolled

November 10, 2015

Completed

3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 17, 2019

Completed

12 months until next milestone

Results Posted

Study results publicly available

July 13, 2020

Completed

2.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 21, 2022

Completed

Last Updated

May 29, 2024

Status Verified

May 1, 2024

Enrollment Period

3.7 years

First QC Date

March 16, 2015

Results QC Date

June 24, 2020

Last Update Submit

May 10, 2024

Conditions

Leukemia, Acute Lymphoblastic

Keywords

ALLHigh-risk first relapse B-precursor ALLPrecursor Cell Lymphoblastic LeukemiaNeoplasmsLymphoproliferative DisordersImmunoproliferative DisordersAntibodies, Bispecific

Outcome Measures

Primary Outcomes (2)

Kaplan Meier Estimate: Event-Free Survival (EFS; Primary Analysis)
EFS is calculated from the time of randomization until the date of relapse or M2 marrow (representative bone marrow aspirate or biopsy with ≥ 5% and \< 25% blasts) after having achieved a complete remission (CR), failure to achieve a CR at the end of treatment, second malignancy, or death due to any cause, whichever occurs first. Participants who failed to achieve a CR following treatment with investigational product (IP) or who died before the disease assessment at the end of treatment were considered treatment failures and assigned an EFS duration of 1 day. Participants still alive and event-free were censored on their last disease assessment date. Participants were said to be in CR when they had the following: * M1 marrow * Peripheral blood without blasts * Absence of extramedullary leukemic involvement Months are calculated as days from randomization date to event/censor date, divided by 30.5.
As of the primary analysis data cutoff date (17 July 2019), overall median follow-up time for EFS was 22.4 months.
Kaplan Meier Estimate: EFS (Final Analysis)
EFS is calculated from the time of randomization until the date of relapse or M2 marrow after having achieved a CR, failure to achieve a CR at the end of treatment, second malignancy, or death due to any cause, whichever occurs first. Participants who failed to achieve a CR following treatment with IP or who died before the disease assessment at the end of treatment were considered treatment failures and assigned an EFS duration of 1 day. Participants still alive and event-free were censored on their last disease assessment date. Participants were said to be in CR when they had the following: * M1 marrow * Peripheral blood without blasts * Absence of extramedullary leukemic involvement Months are calculated as days from randomization date to event/censor date, divided by 30.5.
At final analysis, overall median follow-up time for EFS was 51.9 months.

Secondary Outcomes (10)

Kaplan Meier Estimate: Overall Survival (OS)
At final analysis, overall median follow-up time for OS was 55.2 months.
Percentage of Participants With an MRD Response Within 29 Days of Treatment Initiation
Up to End of Treatment (Cycle 1, Day 29)
Cumulative Incidence of Relapse (CIR)
At final analysis, the overall maximum follow-up time was 82.0 months.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs)
From first dose of IP through the last dose of IP (up to Day 29) plus 30 days.
Number of Participants With TEAEs of Interest
From first dose of IP through the last dose of IP (up to Day 29) plus 30 days.
+5 more secondary outcomes

Study Arms (2)

High Risk Consolidation 3 (HC3) Chemotherapy

ACTIVE COMPARATOR

One week of treatment with HC3 followed by 3 weeks of no treatment. The standard intensive consolidation chemotherapy course HC3 includes dexamethasone (10 mg/m\^2/day intravenous \[IV\] on Days 1-6), vincrisitne (1.5 mg/m\^2/day IV on Days 1 and 6), daunorubicin (30 mg/m\^2 IV over 24 hours on Day 5), methotrexate (1 g/m\^2 IV over 36 hours on Day 1), ifosfamide (800 mg/m\^2 IV for 1 hour on Days 2-4), and pegylated \[PEG\]-asparaginase (1000 U/m\^2 IV for 2 hours or intramuscularly \[IM\] on Day 6) or, if allergic, erwinia-asparaginase (20,000 units/m\^2 IV or IM every 48 hours for a total of 6 doses).

Drug: DexamethasoneDrug: VincrisitneDrug: DaunorubicinDrug: MethotrexateDrug: IfosfamideDrug: PEG-asparaginaseDrug: Erwinia-asparaginase

Blinatumomab

EXPERIMENTAL

15 μg/m\^2/day as a continuous intravenous infusion (CIVI) for 4 weeks

Drug: Blinatumomab

Interventions

BlinatumomabDRUG

15 μg/m\^2/day as a continuous intravenous infusion (CIVI) for 4 weeks

Also known as: Blincyto, AMG103

Blinatumomab

DexamethasoneDRUG

10 mg/m\^2/day intravenous (IV) on Days 1-6