Study of the BiTE® Blinatumomab (MT103) in Adult Patients With Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia (ALL)

NCT01209286 | Completed Phase 2 Results DMC

• 1 other identifier: MT103-206
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study is to determine whether the bispecific T-cell engager blinatumomab is effective, safe and tolerable in the treatment of patients with relapsed/refractory B-precursor ALL.

Conditions

B-ALL

Keywords

Blinatumomab; B-ALL; adult ALL; relapsed ALL; refractory ALL; Leukemia; ALL; Lymphatic diseases; Lymphoproliferative disorders; bispecific antibody; anti-CD19; Immunotherapeutic treatment

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a Best Response of Complete Remission or Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment

  At the end of each infusion period, a bone marrow aspiration/biopsy was performed to evaluate the efficacy of blinatumomab. All hematological assessments of bone marrow were reviewed in a central reference laboratory. Hematological remissions were defined by the following criteria: Complete Response/Remission (CR): * Less than or equal to 5% blasts in the bone marrow * No evidence of circulating blasts or extramedullar disease * Full recovery of peripheral blood counts: * Platelets \> 100,000/μL * Hemoglobin ≥ 11 g/dL * Absolute neutrophil count (ANC) \> 1,500/μL Complete Remission with only Partial Hematological Recovery (CRh\*): * Less than or equal to 5% blasts in the bone marrow * No evidence of circulating blasts or extramedullar disease * Partial recovery of peripheral blood counts: * Platelets \> 50,000/μL * Hemoglobin ≥ 7 g/dL * ANC \> 500/μL.

  Within the first 2 cycles of treatment, 12 weeks

Secondary Outcomes (12)

• Percentage of Participants With a Best Response of Complete Remission Within 2 Cycles of Treatment

  Within the first 2 cycles of treatment, 12 weeks

• Percentage of Participants With a Best Response of Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment

  Within the first 2 cycles of treatment, 12 weeks

• Percentage of Participants With a Best Response of Partial Remission Within 2 Cycles of Treatment

  Within the first 2 cycles of treatment, 12 weeks

• Percentage of Participants With a Minimal Residual Disease (MRD) Response During the Core Study

  During the core study treatment period (up to 30 weeks).

• Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT) After Treatment With Blinatumomab

  Up to the data cut-off date of 15 October 2012; maximum follow up time was 459 days

Study Arms (3)

Blinatumomab 15 μg

EXPERIMENTAL

Participants received blinatumomab 15 μg/m²/day as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.

Biological: Blinatumomab

Blinatumomab 5/15 μg

EXPERIMENTAL

Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, followed by 15 μg/m²/day starting from Week 2 of treatment.

Biological: Blinatumomab

Blinatumomab 5/15/30 μg

EXPERIMENTAL

Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, a dose of 15 μg/m²/day in the subsequent 7 days, followed by 30 μg/m²/day starting from Week 3 of treatment.

Biological: Blinatumomab

Interventions

Blinatumomab BIOLOGICAL

Continuous intravenous infusion over four weeks per treatment cycle

Also known as: AMG103, MT103, BLINCYTO™

Blinatumomab 15 μg; Blinatumomab 5/15 μg; Blinatumomab 5/15/30 μg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with B-precursor ALL relapsed after at least induction and consolidation or having refractory disease
• More than 5% blasts in bone marrow
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Life expectancy of ≥ 12 weeks

You may not qualify if:

• History or presence of clinically relevant central nervous system (CNS) pathology
• Infiltration of cerebrospinal fluid (CSF) by ALL
• Autologous/allogeneic hematopoietic stem cell transplantation (HSCT) within six weeks/three months prior to start of blinatumomab treatment
• Active Graft-versus-Host Disease (GvHD)
• Patients with Philadelphia chromosome (Ph)+ ALL eligible for treatment with dasatinib or imatinib
• Cancer chemotherapy within two weeks prior to start of blinatumomab treatment
• Immunotherapy (e.g. rituximab) within four weeks prior to start of blinatumomab treatment
• Infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive)
• Pregnant or nursing women
• Previous treatment with blinatumomab

Sponsors & Collaborators

• Amgen Research (Munich) GmbH: lead

Study Sites (9)

Unknown Facility

Frankfurt, Germany

Location

Unknown Facility

Freiburg im Breisgau, Germany

Location

Unknown Facility

Hanover, Germany

Location

Unknown Facility

Kiel, Germany

Location

Unknown Facility

Münster, Germany

Location

Unknown Facility

Regensburg, Germany

Location

Unknown Facility

Tübingen, Germany

Location

Unknown Facility

Ulm, Germany

Location

Unknown Facility

Würzburg, Germany

Location

Related Publications (3)

• Nagele V, Kratzer A, Zugmaier G, Holland C, Hijazi Y, Topp MS, Gokbuget N, Baeuerle PA, Kufer P, Wolf A, Klinger M. Changes in clinical laboratory parameters and pharmacodynamic markers in response to blinatumomab treatment of patients with relapsed/refractory ALL. Exp Hematol Oncol. 2017 May 18;6:14. doi: 10.1186/s40164-017-0074-5. eCollection 2017.

  PMID: 28533941 DERIVED

• Zhu M, Wu B, Brandl C, Johnson J, Wolf A, Chow A, Doshi S. Blinatumomab, a Bispecific T-cell Engager (BiTE((R))) for CD-19 Targeted Cancer Immunotherapy: Clinical Pharmacology and Its Implications. Clin Pharmacokinet. 2016 Oct;55(10):1271-1288. doi: 10.1007/s40262-016-0405-4.

  PMID: 27209293 DERIVED

• Topp MS, Gokbuget N, Zugmaier G, Klappers P, Stelljes M, Neumann S, Viardot A, Marks R, Diedrich H, Faul C, Reichle A, Horst HA, Bruggemann M, Wessiepe D, Holland C, Alekar S, Mergen N, Einsele H, Hoelzer D, Bargou RC. Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J Clin Oncol. 2014 Dec 20;32(36):4134-40. doi: 10.1200/JCO.2014.56.3247. Epub 2014 Nov 10.

  PMID: 25385737 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia; Lymphatic Diseases; Lymphoproliferative Disorders

Interventions

blinatumomab

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• Max Topp, MD

  University of Wuerzburg

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2010
• First Posted: September 27, 2010
• Study Start: October 1, 2010
• Primary Completion: March 1, 2012
• Study Completion: October 1, 2016
• Last Updated: March 6, 2017
• Results First Posted: January 7, 2015

Record last verified: 2016-07

Locations

DE (9)