Clinical Study With Blinatumomab in Pediatric and Adolescent Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia

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Brief Title

Clinical Study With Blinatumomab in Pediatric and Adolescent Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia

Official Title

A Single-Arm Multicenter Phase II Study Preceded by Dose Evaluation to Investigate the Efficacy, Safety, and Tolerability of the BiTE® Antibody Blinatumomab (MT103) in Pediatric and Adolescent Patients With Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia (ALL)

Brief Summary

      The purpose of this study is to determine the dose of the bispecific T cell engager
      blinatumomab (MT103) in pediatric and adolescent patients with relapsed/refractory acute
      lymphoblastic leukemia (ALL) and to assess whether this dose of blinatumomab is effective.
    

Detailed Description

      Childhood acute lymphoblastic leukemia (ALL) is a type of cancer of the blood and bone marrow
      in which the bone marrow makes too many abnormal immature lymphocytes.

      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 cluster of
      differentiation (CD)19 expressing cells.

      The purpose of this study is to investigate the pharmacokinetics (PK), pharmacodynamics (PD)
      and safety of escalating doses of blinatumomab in pediatric and adolescent patients with
      relapsed/refractory B-precursor ALL, to select a dose and to investigate the efficacy and
      safety of that dose of blinatumomab in the above-mentioned patient population.

      The phase 1 part of the study included the evaluation of four dose levels of blinatumomab
      with comprehensive PK/PD assessments and was separated in 2 parts:

        -  Phase 1 dose evaluation/escalation part to define the recommended phase 2 dose of
           blinatumomab in patients aged 2 to 17 years

        -  Phase 1 PK expansion part in patients aged < 18 years to further assess PK/PD at the
           recommended phase 2 dose. In this part additional participants were enrolled to ensure
           that 6 patients in each of the 2 older age groups (2-6 and 7-17 years) were analyzed for
           PK before recruitment of infants < 2 years of age began.

      In the phase 2 extension cohort (efficacy phase) of the study, eligible participants less
      than 18 years were enrolled according to a two-stage design and received blinatumomab at the
      recommended dose level (5/15 μg/m²/day).

      The study consisted of a screening period, a treatment period, and an End of Core Study visit
      30 days after last dose of study medication. A treatment cycle consisted of a continuous
      intravenous (cIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks.
      Participants who achieved complete remission (CR) within 2 cycles of treatment could receive
      up to 3 additional consolidation cycles of blinatumomab. Instead of consolidation cycles with
      blinatumomab, participants could be withdrawn from blinatumomab treatment to receive
      chemotherapy or allogeneic HSCT as early as the first cycle, at the discretion of the
      investigator.

      After the last treatment cycle and End of Core Study visit, all participants were followed
      for efficacy and survival for up to 24 months after treatment start. Participants who
      suffered a hematological relapse of B-precursor ALL during their follow-up period (at least 3
      months after completion of treatment) had the possibility for retreatment with blinatumomab.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Phase I: Number of Participants With Dose-limiting Toxicities (DLTs)

Secondary Outcome

 Number of Participants With Adverse Events

Condition

Acute Lymphoblastic Leukemia

Intervention

Blinatumomab

Study Arms / Comparison Groups

 Blinatumomab
Description:  Blinatumomab was administered as a continuous intravenous (cIV) infusion at a constant daily flow rate over 4 weeks followed by a treatment-free interval of 2 weeks. Doses ranged between 5 and 30 µg/m²/day. Each participant received up to five cycles of treatment.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

93

Start Date

January 2012

Completion Date

May 2016

Primary Completion Date

August 2014

Eligibility Criteria

        Inclusion Criteria:

          -  Morphologic evidence of B-precursor ALL with > 25% blasts in bone marrow (M3) at study
             enrolment

          -  Age less than 18 years at enrollment

          -  Relapsed/refractory disease:

               -  Second or later bone marrow relapse,

               -  Any marrow relapse after allogeneic hematopoietic stem cell transplantation
                  (HSCT), or

               -  Refractory to other treatments: Patients in first relapse must have failed to
                  achieve a CR following full standard reinduction chemotherapy regimen of at least
                  4 weeks duration. Patients who have not achieved a first remission must have
                  failed a full standard induction regimen

          -  Karnofsky performance status more than or equal to 50% for patients more than or equal
             to 16 years and Lansky Performance Status (LPS) of more than or equal to 50% for
             patients less than 16 years

          -  Organ function requirements: All patients must have adequate renal and liver functions

        Exclusion Criteria:

          -  Active acute or extensive chronic graft-versus-host disease (GvHD)

          -  Immunosuppressive agents to prevent or treat GvHD within 2 weeks prior to blinatumomab
             treatment

          -  Evidence for current central nervous system (CNS) involvement by ALL (CNS 2, CNS 3) or
             testicular involvement by ALL

          -  History of relevant CNS pathology or current relevant CNS pathology

          -  History of autoimmune disease with potential CNS involvement or current autoimmune
             disease

          -  Any HSCT within 3 months prior to blinatumomab treatment

          -  Cancer chemotherapy within 2 weeks prior to blinatumomab treatment (except for
             intrathecal chemotherapy and/or low dose maintenance therapy such as vinca alkaloids,
             mercaptopurine, methotrexate, glucocorticoids)

          -  Chemotherapy related toxicities that haven't resolved to less than or equal to Grade 2

          -  Radiotherapy within 2 weeks prior to blinatumomab treatment

          -  Immunotherapy (e.g. rituximab, alemtuzumab) within 6 weeks prior to blinatumomab
             treatment

          -  Any investigational product within 4 weeks prior to study entry

          -  Previous treatment with blinatumomab

          -  Active severe infection, any other concurrent disease or medical condition that could
             be exacerbated by the treatment or would seriously complicate compliance with the
             protocol

          -  Known infection with human immunodeficiency virus (HIV) or chronic infection with
             hepatitis B virus (HbsAg positive) or hepatitis C virus (anti-HCV positive)
      

Gender

All

Ages

N/A - 17 Years

Accepts Healthy Volunteers

No

Contacts

Arend von Stackelberg, MD, , 

Location Countries

Austria

Location Countries

Austria

Administrative Informations


NCT ID

NCT01471782

Organization ID

MT103-205

Secondary IDs

2010-024264-18

Responsible Party

Sponsor

Study Sponsor

Amgen Research (Munich) GmbH


Study Sponsor

Arend von Stackelberg, MD, Study Chair, Charite University, Berlin, Germany


Verification Date

December 2016