Clinical Trials /

Study of Blinatumomab in Japanese Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia

NCT02412306

Description:

This is an open-label, combined 2-part multicenter study to evaluate the efficacy, safety, and tolerability of blinatumomab in adult and pediatric Japanese patients with relapsed/refractory B-precursor ALL.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Blinatumomab in Japanese Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia
  • Official Title: A Phase 1b/2 Study of Blinatumomab in Japanese Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL) (Horai Study)

Clinical Trial IDs

  • ORG STUDY ID: 20130265
  • NCT ID: NCT02412306

Conditions

  • Relapsed Refractory B Precursor Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
BlinatumomabBlincyto®Blinatumomab

Purpose

This is an open-label, combined 2-part multicenter study to evaluate the efficacy, safety, and tolerability of blinatumomab in adult and pediatric Japanese patients with relapsed/refractory B-precursor ALL.

Detailed Description

      The Phase 1b part will investigate the safety, efficacy, pharmacokinetics (PK) and
      pharmacodynamics (PD) of blinatumomab to determine the maximum tolerated dose (MTD) in both
      adult and pediatric Japanese patients with relapsed/refractory B-precursor ALL. The Phase 2
      part will assess the safety and efficacy of the recommended dose level of blinatumomab
      identified in the Phase 1b portion of the study in the adult study population.

      In June 2017 protocol amendment 4 extended the study to include an expansion cohort of
      approximately 65 participants to investigate the safety of blinatumomab in participants who
      did not participate in Phase 1b or Phase 2 of the study. Adult and pediatric patients in the
      expansion cohort may receive up to 5 cycles of investigational blinatomumab and may receive
      commercial blinatomumab after a minimum of 2 cycles of the investigational drug. The
      expansion cohort is currently enrolling.
    

Trial Arms

NameTypeDescriptionInterventions
BlinatumomabExperimentalParticipants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose for adults was 9 μg/day for the first week of cycle 1, escalated to 28 μg/day starting from Week 2 and all cycles thereafter. For pediatric participants the initial dose was 5 µg/m²/day for the first week of cycle 1, escalated to 15 µg/m²/day starting from week 2 and all cycles thereafter.
  • Blinatumomab

Eligibility Criteria

        Adult Subjects Key Inclusion Criteria:

          -  Age ≥ 18 years old at enrollment

          -  Subjects with Philadelphia-negative B-precursor ALL, with any of the following:

               -  Relapsed or refractory after first line therapy with first remission duration ≤
                  12 months; or

               -  Relapsed or refractory after first salvage therapy; or

               -  Relapsed or refractory within 12 months of allogeneic hematopoietic stem cell
                  transplant (alloHSCT)

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.

          -  Greater than 5% blasts in bone marrow

        Pediatric Subjects Key Inclusion Criteria:

          -  Age < 18 years old at enrollment

          -  Relapsed/refractory disease, defined as one of the following:

               -  second or later bone marrow relapse;

               -  any marrow relapse after alloHSCT; or

               -  Refractory to other treatments:

                    -  For subjects in first relapse: failure to achieve a CR following a full
                       standard reinduction chemotherapy regimen

                    -  For subjects who have not achieved a first remission: failure to achieve
                       remission following a full standard induction regimen

          -  Greater than 5% blasts in bone marrow

          -  Karnofsky performance status ≥ 50% for subjects ≥ 16 years

          -  Lansky performance status ≥ 50% for subjects < 16 years

        Key Exclusion Criteria

          -  Subjects with Burkitt´s Leukemia according to World Health Organization (WHO)
             classification

          -  History or presence of clinically relevant central nervous system (CNS) pathology such
             as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia,
             Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis; with the
             exception of well-controlled CNS leukemia

          -  Active ALL in the CNS or testes

          -  Current autoimmune disease or history of autoimmune disease with potential CNS
             involvement

          -  Autologous HSCT within 6 weeks prior to start of blinatumomab treatment

          -  AlloHSCT within 12 weeks prior to start of blinatumomab treatment

          -  Any active acute Graft-versus-Host Disease (GvHD) grade 2-4 according to Glucksberg
             criteria or active chronic GvHD requiring systemic treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Primary Endpoint phase 1= Incidence of DLT (dose limiting toxicities)
Time Frame:Primary outcome will be assessed within 12 weeks of treatment with blinatumomab
Safety Issue:
Description:Phase 1b Primary Endpoint Incidence of DLTs. DLTs are defined as greater or equal to grade 3 adverse event related to blinatumomab (CTCAE v4.0).

Secondary Outcome Measures

Measure:Phase 1 the incidence and severity of adverse events
Time Frame:within 12 weeks of blinatumomab treatment
Safety Issue:
Description:To determine the incidence and severity of adverse events as assessed by CTCAE v4.0
Measure:Phase 1 the numer of subjects with complete remission
Time Frame:Within 12 week of treatment with blinatumomab
Safety Issue:
Description:To determine the number of subjects with complete remission (CR/CR*h/CRi)
Measure:Phase 1 time to hematological relapse
Time Frame:up to 33 monts
Safety Issue:
Description:To determine time to hematological relapse (TTHR)
Measure:Phase 1 overall survival (OS)
Time Frame:up to 33 months
Safety Issue:
Description:Determine overall survival
Measure:Phase 1 Relapse free survival (RFS)
Time Frame:up to 33 months
Safety Issue:
Description:Determine Relapse free survival duration
Measure:Phase 1 blinatumomab PK parameters
Time Frame:within up to 30 weeks of treatment start
Safety Issue:
Description:To measure PK parameters (steady state concentrations and clearance of blinatumomab)
Measure:Phase 1 serum cytokine concentrations
Time Frame:within up to 30 weeks of treatment start
Safety Issue:
Description:To measure serum cytokine concentrations
Measure:Phase 1 incidence of anti-blinatumomab antibody formation
Time Frame:up to 34 weeks after treatment
Safety Issue:
Description:To determine incidence of anti-blinatumomab formation
Measure:Phase 2 duration of response (TTHR)
Time Frame:up to 33 months
Safety Issue:
Description:To measure Time to hematological relapse
Measure:Phase 2 AlloHSCT after treatment with blinatumomab
Time Frame:up to 33 months
Safety Issue:
Description:To determine the rate of Allogeneic HCST (alloHCST) treatment with blinatumomab
Measure:Phase 2 the best overall response
Time Frame:12 weeks
Safety Issue:
Description:To determine the best overall response rate
Measure:Phase 2 overall survival
Time Frame:up to 33 months
Safety Issue:
Description:To determine the rate of overall survival (OS)
Measure:Phase 2 rate of relapse free survival
Time Frame:up to 33 months
Safety Issue:
Description:To determine the rate of relapse free survival (RFS)
Measure:Phase 2 incidence and severity of advese events
Time Frame:up to 33 months
Safety Issue:
Description:To determine incidence and severity of adverse events as measured by CTCAE v4.0
Measure:Phase 2 the 100-day mortality after alloHSCT
Time Frame:100-days
Safety Issue:
Description:To determine the 100-day mortality rate after allogeneic hematopoietic stem cell transplant
Measure:Phase 2 PK parameters
Time Frame:up to 30 weeks
Safety Issue:
Description:To measure blinatumomab PK parameters (steady state concentration and clearance of blinatumomab)
Measure:Phase 2 serum cytokine concentrations
Time Frame:up to 30 weeks
Safety Issue:
Description:To measure serum cytokine concentrations
Measure:Phase 2 anti-blinatumomab antibody formation
Time Frame:up to 34 weeks after treatment start
Safety Issue:
Description:To determine incidence of anti-blinatumomab formation
Measure:Phase 1 Duration of CR/CRh*/CRi
Time Frame:up to 33 months
Safety Issue:
Description:To determine duration of complete remission
Measure:Phase 2 Duration of CR/CRh*/CRi
Time Frame:up to 33 months
Safety Issue:
Description:To determine duration of complete remission
Measure:Expansion Cohort
Time Frame:Within 12 weeks of treatment with blinatumomab
Safety Issue:
Description:CR/CRh* within first 2 cycles of treatment with blinatumomab for adults and M1 remission within the first 2 cycles of treatment with blinatumomab in pediatric subjects.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Amgen

Trial Keywords

  • Amgen

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