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

NCT01471782 | Completed Phase 1 Results DMC

• 2 other identifiers: MT103-2052010-024264-18
• Study Type: interventional
• Target: 93
• Locations: 7 countries
• Sites: 30

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.

Conditions

Acute Lymphoblastic Leukemia

Keywords

ALL; relapsed, refractory B-precursor ALL; Leukemia; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Antibodies, Bispecific

Outcome Measures

Primary Outcomes (2)

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

  The maximum tolerated dose (MTD) was defined as one or fewer out of 6 participants experiencing a dose limiting toxicity (DLT) or the maximum administered dose (MAD). A dose limiting toxicity is any Grade ≥ 3 adverse event related to study drug, Grade 3 fatigue, headache, insomnia, fever, hypotension or infection were not considered dose limiting toxicities. Laboratory parameters of Grade ≥ 3 but not considered as clinically relevant and/or responding to routine medical management, thrombocytopenia, leukopenia (including neutropenia and lymphopenia), and anemia were not considered dose limiting toxicities.

  Cycle 1, 28 days

• Percentage of Participants With Complete Remission in the First Two Cycles

  Hematological assessments were performed from bone marrow biopsy samples. All hematological assessments of bone marrow were reviewed in a central laboratory. Complete remission (CR) was defined as * M1 bone marrow (bone marrow blasts \< 5%) * No evidence of circulating blasts or extra-medullary disease Complete remission includes participants with incomplete recovery of peripheral blood counts.

  Cycles 1 and 2 (12 weeks)

Secondary Outcomes (8)

• Number of Participants With Adverse Events

  From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 28 days

• Steady State Concentration of Blinatumomab

  Cycles 1 and 2 during the IV infusion on day 3 (at least 48 hours after start of infusion) and days 8, 15 and 22 (steady state) and day 29 at End of Infusion (EoI) and 2, 4, and 8 hours after EoI for ages ≥ 2 years.

• Time to Hematological Relapse (Duration of Response)

  Up to the data cut-off date of 12 January 2015; median observation time was 23.5 months for phase 1 and 11.5 months for phase 2.

• Overall Survival

  Up to the data cut-off date of 12 January 2015; median observation time was 23.5 months for phase 1 and 11.6 months for phase 2.

• Relapse-free Survival

  Up to the data cut-off date of 12 January 2015; median observation time was 23.5 months for phase 1 and 11.5 months for phase 2.

Study Arms (1)

Blinatumomab

EXPERIMENTAL

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.

Biological: Blinatumomab

Interventions

Blinatumomab BIOLOGICAL

Administered by continuous intravenous infusion

Also known as: MT103, AMG103, BLINCYTO®

Blinatumomab

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Amgen Research (Munich) GmbH: lead

Study Sites (30)

Children's Hospital Denver

Aurora, Colorado, 80045, United States

Location

Children's Healthcare of Atlanta at Egleston

Atlanta, Georgia, 30322, United States

Location

Washington University

St Louis, Missouri, United States

Location

Memorial Sloan Kettering

New York, New York, 10065, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

St Jude Children's Research Hospital

Memphis, Tennessee, 38105-3678, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390-9063, United States

Location

Texas Children's Cancer Center/ Baylor

Houston, Texas, 77030-2399, United States

Location

Primary Children's Medical Center

Salt Lake City, Utah, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

St. Anna Kinderspital

Vienna, 1090, Austria

Location

Hospital for Sick Children

Toronto, Ontario, M5G1X8, Canada

Location

(CHU Besancon) Hopital Saint-Jaques

Besançon, 25030, France

Location

Hôpital de la Timone (Enfants)

Marseille, France

Location

Hopital Robert Debré (AP-HP)

Paris, 75935, France

Location

Charité Campus Virchow Klinikum, Otto-Heubner-Centrum (OHC) für Kinder- und Jugendmedizin

Berlin, 13353, Germany

Location

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

Location

Universitätsklinikum Essen

Essen, Germany

Location

Klinikum der Johann Wolfgang Goethe-Universität Frankfurt/Main

Frankfurt am Main, 60590, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, Germany

Location

Medizinische Hochschule Hannover

Hanover, Germany

Location

Universitätsklinikum Schleswig-Holstein Campus Kiel

Kiel, Germany

Location

Klinikum der Universität München, Dr. von Haunersches Kinderspital

München, 80337, Germany

Location

Universitätsklinik für Kinder- und Jugendmedizin Tübingen

Tübingen, 72076, Germany

Location

Universitätsklinikum Würzburg

Würzburg, Germany

Location

University of Milano-Bicocca, Hospital San Gerardo

Monza, 20052, Italy

Location

Dipartimento della Donna e del Bambino

Padua, Italy

Location

The Bambino Gesù Children's Hospital

Rome, 00165, Italy

Location

Erasmus MC, Sophia Children's Hospital

Rotterdam, 3015 GJ, Netherlands

Location

Related Publications (1)

• von Stackelberg A, Locatelli F, Zugmaier G, Handgretinger R, Trippett TM, Rizzari C, Bader P, O'Brien MM, Brethon B, Bhojwani D, Schlegel PG, Borkhardt A, Rheingold SR, Cooper TM, Zwaan CM, Barnette P, Messina C, Michel G, DuBois SG, Hu K, Zhu M, Whitlock JA, Gore L. Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia. J Clin Oncol. 2016 Dec 20;34(36):4381-4389. doi: 10.1200/JCO.2016.67.3301. Epub 2016 Oct 31.

  PMID: 27998223 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Burkitt Lymphoma; Leukemia; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders

Interventions

blinatumomab

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Results Point of Contact

• Title: Study Director
• Organization: Amgen, Inc

866-572-6436

Study Officials

• Arend von Stackelberg, MD

  Charite University, Berlin, Germany

  STUDY CHAIR

• Lia Gore, MD

  Children's Hospital Denver, USA

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2011
• First Posted: November 16, 2011
• Study Start: January 1, 2012
• Primary Completion: August 1, 2014
• Study Completion: May 1, 2016
• Last Updated: February 8, 2017
• Results First Posted: February 8, 2017

Record last verified: 2016-12

Locations

CA (1); FR (3); DE (10); IT (3); US (11); AU (1); NL (1)