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

Acute Lymphoblastic Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01471782
• Other study ID #: MT103-205
• Secondary ID: 2010-024264-18
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 28, 2011
• Last updated: July 12, 2016
• Start date: January 2012
• Est. completion date: May 2016

Study information

• Verified date: July 2016
• Source: Amgen Research (Munich) GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-InstitutUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

Relapsed/refractory B-precursor ALL in pediatric and adolescent patients is an aggressive malignant disease with dismal prognosis. Apart from allogeneic hematological stem cell transplantation (HSCT) there is not any other curative treatment of second relapse or refractory B-precursor ALL available. Additional 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. The purpose of this study is to investigate the pharmacokinetics, pharmacodynamics and safety of escalating doses of the BiTE® antibody blinatumomab (MT103)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 above mentioned patient population. Patients will receive up to five 6-weeks cycles (4 weeks of continuous intravenous infusion followed by a 2-weeks treatment free interval) of blinatumomab treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: May 2016
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 17 Years

Eligibility

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 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 GvHD

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

• Evidence for current 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)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• blinatumomab
intravenous infusion

Locations

Country	Name	City	State
Austria	St. Anna Kinderspital	Vienna
Canada	Hospital for Sick Children	Toronto	Ontario
France	(CHU Besancon) Hopital Saint-Jaques	Besancon
France	Hôpital de la Timone (Enfants)	Marseille
France	Hopital Robert Debré (AP-HP)	Paris Cedex 19
Germany	Charité Campus Virchow Klinikum, Otto-Heubner-Centrum (OHC) für Kinder- und Jugendmedizin	Berlin
Germany	Universitätsklinikum Düsseldorf	Düsseldorf
Germany	Universitätsklinikum Essen	Essen
Germany	Klinikum der Johann Wolfgang Goethe-Universität Frankfurt/Main	Frankfurt am Main
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinikum Schleswig-Holstein Campus Kiel	Kiel
Germany	Klinikum der Universität München, Dr. von Haunersches Kinderspital	München
Germany	Universitätsklinik für Kinder- und Jugendmedizin Tübingen	Tübingen
Germany	Universitätsklinikum Würzburg	Würzburg
Italy	University of Milano-Bicocca, Hospital San Gerardo	Monza
Italy	Dipartimento della Donna e del Bambino	Padova
Italy	The Bambino Gesù Children's Hospital	Rome
Netherlands	Erasmus MC, Sophia Children's Hospital	Rotterdam
United States	Children's Healthcare of Atlanta at Egleston	Atlanta	Georgia
United States	Children's Hospital Denver	Aurora	Colorado
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Texas Children's Cancer Center/ Baylor	Houston	Texas
United States	St Jude Children's Research Hospital	Memphis	Tennessee
United States	Memorial Sloan Kettering	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	Seattle Children's Hospital	Seattle	Washington
United States	Washington University	ST. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Amgen Research (Munich) GmbH

Countries where clinical trial is conducted

United States,  Austria,  Canada,  France,  Germany,  Italy,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase I part: Maximal tolerable dose	Maximal tolerable dose defined by <= 1 of 6 patients experiencing dose limiting toxicity or maximal administered dose	within 2 years	Yes
Primary	Phase II part: Rate of complete remission (CR)		within 10 weeks	No
Secondary	Overall incidence and severity of adverse events		within 3 years	Yes
Secondary	Proportion of patients who undergo allogeneic HSCT after treatment with blinatumomab		within 2 years	No
Secondary	CR duration		within 2 years	No
Secondary	Overall survival		within 2 years	No
Secondary	Steady state concentration of blinatumomab (pharmacokinetics)		within 2 years	No
Secondary	Cytokine serum concentrations		within 2 years	Yes
Secondary	Time to hematological relapse		within 2 years	No