Blinatumomab in Adults With Relapsed/Refractory Philadelphia Positive B-precursor Acute Lymphoblastic Leukemia

May 10, 2024 updated by: Amgen

A Phase 2 Single Arm, Multicenter Trial to Evaluate the Efficacy of the BiTE Antibody Blinatumomab in Adult Subjects With Relapsed/Refractory Philadelphia Positive B-precursor Acute Lymphoblastic Leukemia (Alcantara Study)

The primary objective is to evaluate the rate of complete remission/complete remission with partial hematological recovery (CRh*) in adults with relapsed/refractory Philadelphia chromosome positive (Ph+) B-precursor acute lymphoblastic leukemia (ALL) who receive blinatumomab.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a single-arm Simon II stage design, multicenter study consisting of a screening period, an induction treatment period (2 cycles of blinatumomab), a consolidation treatment period (up to 3 additional cycles of blinatumomab for applicable participants), and a safety follow-up visit 30 days after treatment. Following the safety follow-up visit, participants will be followed for response duration and survival every 3 months for 18 months or death, whichever occurs first.

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Nantes Cedex 1, France, 44093
        • Research Site
      • Paris Cedex 10, France, 75475
        • Research Site
      • Toulouse cedex 9, France, 31059
        • Research Site
  • Germany
      • Berlin, Germany, 12200
        • Research Site
      • Essen, Germany, 45122
        • Research Site
      • Frankfurt am Main, Germany, 60590
        • Research Site
      • Würzburg, Germany, 97080
        • Research Site
  • Italy
      • Bergamo, Italy, 24127
        • Research Site
      • Bologna, Italy, 40138
        • Research Site
      • Roma, Italy, 00161
        • Research Site
      • Venezia, Italy, 30174
        • Research Site
      • Verona, Italy, 37134
        • Research Site
  • United Kingdom
      • London, United Kingdom, NW3 2PF
        • Research Site
      • Sutton, United Kingdom, SM2 5PT
        • Research Site
  • United States
    • California
      • Duarte, California, United States, 91010
        • Research Site
      • La Jolla, California, United States, 92093-0960
        • Research Site
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Research Site
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Research Site
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Research Site
    • New York
      • New York, New York, United States, 10065
        • Research Site
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Research Site
    • Texas
      • Houston, Texas, United States, 77030
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  • Patients with Ph+ B-precursor ALL, with any of the following:

    • Relapsed or refractory to at least one second generation tyrosine kinase inhibitor (TKI) (dasatinib, nilotinib, bosutinib, ponatinib)
    • OR intolerant to second generation TKI and intolerant or refractory to imatinib mesylate
  • Greater than 5% blasts in bone marrow
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Age ≥ 18 years of age, 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.

Exclusion Criteria

  • History of malignancy other than ALL within 5 years prior to start of protocol-required therapy, except for adequately treated selected cancers without evidence of disease
  • History or presence of clinically relevant central nervous system (CNS) pathology as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis
  • Active ALL in the CNS or testes
  • Isolated extramedullary disease
  • Current autoimmune disease or history of autoimmune disease with potential CNS involvement
  • Allogeneic hematopoietic stem cell transplantation (HSCT) within 12 weeks before blinatumomab treatment
  • Active acute or extensive chronic graft-versus-host disease (GvHD) which included the administration of immunosuppressive agents to prevent or treat GvHD within 2 weeks before blinatumomab treatment
  • immediately previous cancer chemotherapy, radiotherapy, or immunotherapy; and eligibility for allogeneic HSCT at the time of enrollment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Blinatumomab

Participants will receive blinatumomab by continuous intravenous (CIVI) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for 2 cycles. Participants who achieve a complete remission or complete remission with partial or incomplete hematologic recovery within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab.

The initial dose will be 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 for all subsequent cycles of treatment.
Drug: Blinatumomab
Blinatumomab is administered as a continuous intravenous infusion (CIV). A single cycle of blinatumomab treatment is 6 weeks in duration, which includes 4 weeks of blinatumomab followed by a 2-week treatment-free interval.
Other Names:
  • AMG 103
  • Blincyto®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Complete Remission/Complete Remission With Partial Hematological Recovery (CR/CRh*) During the First Two Treatment Cycles
Time Frame: Approximately 12 weeks, as of the data cut-off date of 20 May 2015

Participants were evaluated for efficacy at the end of each treatment cycle via a central bone marrow aspiration and local peripheral blood counts.

Complete remission was defined as meeting all 3 of the following criteria:

  • less than or equal to 5% blasts in the bone marrow;
  • no evidence of disease
  • full recovery of peripheral blood counts: platelets > 100,000/μl, and absolute neutrophil count (ANC) > 1000/μl.

Complete remission with partial hematological recovery (CRh*) was defined as meeting all 3 of the following criteria:

  • less than or equal to 5% blasts in the bone marrow
  • no evidence of disease
  • partial recovery of peripheral blood counts: platelets > 50,000/μl, and ANC > 500/μl.

Participants without a post-baseline disease assessment were considered non-responders.
Approximately 12 weeks, as of the data cut-off date of 20 May 2015

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Minimal Residual Disease (MRD) Remission During the First 2 Cycles of Treatment
Time Frame: Approximately 12 weeks

Bone marrow samples were evaluated for MRD remission by a central laboratory using bcr-abl fusion gene reverse transcription polymerase chain reaction (RT-PCR).

An MRD response was defined as MRD < 10^-4 measured by PCR. Participants with no post-baseline MRD assessment were considered non-responders.
Approximately 12 weeks
Duration of CR or CRh* Response
Time Frame: Up to the data cut-off date of 20 May 2015; median observation time was 7.0 months
Duration of response was measured for participants in remission (CR/CRh*), and was measured from the time the participant first achieved remission until first documented relapse or death from disease progression. Participants without a documented relapse (hematological or extramedullary) and who did not die were censored at the time of the last bone marrow assessment or the last survival follow-up visit to confirm remission. Participants who died without having reported hematological relapse or without showing any clinical sign of disease progression were censored on their date of death.
Up to the data cut-off date of 20 May 2015; median observation time was 7.0 months
Percentage of Participants With Complete Remission (CR) During the First Two Treatment Cycles
Time Frame: Approximately 12 weeks, as of the data cut-off date of 20 May 2015

Participants were evaluated for efficacy at the end of each treatment cycle via a central bone marrow aspiration and local peripheral blood counts.

Complete remission was defined as meeting all 3 of the following criteria:

  • less than or equal to 5% blasts in the bone marrow;
  • no evidence of disease;
  • full recovery of peripheral blood counts: platelets > 100,000/μl, and absolute neutrophil count (ANC) > 1000/μl.

Participants without a post-baseline disease assessment were considered non-responders.
Approximately 12 weeks, as of the data cut-off date of 20 May 2015
Percentage of Participants With Complete Remission With Partial Hematological Recovery (CRh*) During the First Two Treatment Cycles
Time Frame: Approximately 12 weeks, as of the data cut-off date of 20 May 2015

Participants were evaluated for efficacy at the end of each treatment cycle via a central bone marrow aspiration and local peripheral blood counts.

Complete remission with partial hematological recovery (CRh*) was defined as meeting all 3 of the following criteria:

  • less than or equal to 5% blasts in the bone marrow;
  • no evidence of disease;
  • partial recovery of peripheral blood counts: platelets > 50,000/μl, and ANC > 500/μl.

Participants without a post-baseline disease assessment were considered non-responders.
Approximately 12 weeks, as of the data cut-off date of 20 May 2015
Percentage of Participants With Complete Remission/Complete Remission With Partial Hematological Recovery/Complete Remission With Incomplete Hematological Recovery (CR/CRh*/CRi) During the First Two Treatment Cycles
Time Frame: Approximately 12 weeks, as of the data cut-off date of 20 May 2015

Efficacy was evaluated via a central bone marrow aspiration and local peripheral blood counts.

Complete remission was defined as meeting the following criteria:

  • less than or equal to 5% blasts in the bone marrow;
  • no evidence of disease;
  • full recovery of peripheral blood counts: platelets > 100,000/μl, and absolute neutrophil count (ANC) > 1000/μl.

Complete remission with partial hematological recovery was defined as meeting the following criteria:

  • less than or equal to 5% blasts in the bone marrow;
  • no evidence of disease;
  • partial recovery of peripheral blood counts: platelets > 50,000/μl, and ANC > 500/μl.

Complete remission with incomplete hematologic recovery was defined as meeting all of the following criteria:

  • less than or equal to 5% blasts in the bone marrow;
  • no evidence of disease;
  • incomplete recovery of peripheral blood counts: platelets > 100,000/μl or ANC > 1000/μl.

Participants without a post-baseline disease assessment were considered non-responders.
Approximately 12 weeks, as of the data cut-off date of 20 May 2015
Overall Survival
Time Frame: From first dose of blinatumomab until the data cut-off date; median observation time was 8.8 months.

Overall survival was assessed from the date the participant received the first infusion of blinatumomab until death from any cause or the date of the last follow-up.

Participants still alive at the data cut-off date were censored on the last documented visit date or the date of the last contact when the patient was last known to have been alive.
From first dose of blinatumomab until the data cut-off date; median observation time was 8.8 months.
Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT) During Blinatumomab Induced Remission
Time Frame: Up to the data cut-of date of 20 May 2015; Maximum duration on study was 14.5 months.
Participants who achieved remission (CR/CRh*) during the first 2 cycles of treatment and received an allogeneic HSCT.
Up to the data cut-of date of 20 May 2015; Maximum duration on study was 14.5 months.
100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplant
Time Frame: From the date of allogeneic HSCT until the data cut-off date of 20 May 2015; median observation time was 3.2 months.

The analysis of 100-day mortality after allogeneic HSCT was assessed for participants who received an allogeneic HSCT while in remission (CR/CRh*) after 2 cycles of blinatumomab treatment and did not receive any additional antileukemic treatment. 100-day mortality after allogeneic HSCT was calculated relative to the date of allogeneic HSCT.

The 100-day mortality rate after allogeneic HSCT was defined as the percentage of participants having died up to 100 days after allogeneic HSCT estimated using the estimated time to death in percent calculated by Kaplan-Meier methods. Participants alive were censored on the last documented visit date or the date of the last phone contact when the patient was last known to have been alive.
From the date of allogeneic HSCT until the data cut-off date of 20 May 2015; median observation time was 3.2 months.
Number of Participants With Adverse Events
Time Frame: From the first dose of blinatumomab until 30 days after the last dose, up to the cut-off date of 20 May 2015; the median duration of treatment was 53.8 days.

Adverse events (AEs) were graded for severity according to the CTCAE version 4.0, where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.

Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living.

Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living.

Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. Treatment-related adverse events (TRAEs) were those assessed by the investigator as possibly related to blinatumomab based on response to the question: Is there a reasonable possibility that the event may have been caused by blinatumomab or other protocol-specified therapies/procedures?
From the first dose of blinatumomab until 30 days after the last dose, up to the cut-off date of 20 May 2015; the median duration of treatment was 53.8 days.
Number of Participants Who Developed Anti-blinatumomab Antibodies
Time Frame: Day 29 of each treatment period and 30 days after the last dose
Anti-blinatumomab binding antibodies were evaluated with a validated blinatumomab anti-drug antibody assay with the electrochemiluminescence detection technology.
Day 29 of each treatment period and 30 days after the last dose
Steady State Concentration of Blinatumomab
Time Frame: Cycle 1, day 8, 6 to 8 hours after the dose step to 28 μg/day, and Cycle 2, day 1, 6 to 8 hours after blinatumomab infusion
Cycle 1, day 8, 6 to 8 hours after the dose step to 28 μg/day, and Cycle 2, day 1, 6 to 8 hours after blinatumomab infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amgen

Investigators

  • Study Director: MD, Amgen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 3, 2014

Primary Completion (Actual)

May 20, 2015

Study Completion (Actual)

January 6, 2017

Study Registration Dates

First Submitted

November 15, 2013

First Submitted That Met QC Criteria

November 26, 2013

First Posted (Estimated)

December 4, 2013

Study Record Updates

Last Update Posted (Actual)

May 28, 2024

Last Update Submitted That Met QC Criteria

May 10, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20120216
  • 2006-006520-19 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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