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

NCT02000427 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 201202162006-006520-19
• Study Type: interventional
• Target: 45
• Locations: 5 countries
• Sites: 22

Brief Summary

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.

Conditions

Relapsed/Refractory Philadelphia Positive B-precursor ALL

Keywords

Relapsed; Refractory; Philadelphia Positive; B-precursor; Acute Lymphoblastic Leukemia; ALL; Blinatumomab; Leukemia;

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Complete Remission/Complete Remission With Partial Hematological Recovery (CR/CRh*) During the First Two Treatment Cycles

  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 Outcomes (11)

• Percentage of Participants With Minimal Residual Disease (MRD) Remission During the First 2 Cycles of Treatment

  Approximately 12 weeks

• Duration of CR or CRh* Response

  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

  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

  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

  Approximately 12 weeks, as of the data cut-off date of 20 May 2015

Study Arms (1)

Blinatumomab

EXPERIMENTAL

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

Interventions

Blinatumomab DRUG

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.

Also known as: Blincyto®, AMG 103

Blinatumomab

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (22)

Research Site

Duarte, California, 91010, United States

Location

Research Site

La Jolla, California, 92093-0960, United States

Location

Research Site

Atlanta, Georgia, 30322, United States

Location

Research Site

Rochester, Minnesota, 55905, United States

Location

Research Site

St Louis, Missouri, 63110, United States

Location

Research Site

New York, New York, 10065, United States

Location

Research Site

Durham, North Carolina, 27710, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

Nantes, 44093, France

Location

Research Site

Paris, 75475, France

Location

Research Site

Toulouse, 31059, France

Location

Research Site

Berlin, 12200, Germany

Location

Research Site

Essen, 45122, Germany

Location

Research Site

Frankfurt am Main, 60590, Germany

Location

Research Site

Würzburg, 97080, Germany

Location

Research Site

Bergamo, 24127, Italy

Location

Research Site

Bologna, 40138, Italy

Location

Research Site

Roma, 00161, Italy

Location

Research Site

Venezia, 30174, Italy

Location

Research Site

Verona, 37134, Italy

Location

Research Site

London, NW3 2PF, United Kingdom

Location

Research Site

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (8)

• Martinelli G, Boissel N, Chevallier P, Ottmann O, Gokbuget N, Topp MS, Fielding AK, Rambaldi A, Ritchie EK, Papayannidis C, Sterling LR, Benjamin J, Stein A. Complete Hematologic and Molecular Response in Adult Patients With Relapsed/Refractory Philadelphia Chromosome-Positive B-Precursor Acute Lymphoblastic Leukemia Following Treatment With Blinatumomab: Results From a Phase II, Single-Arm, Multicenter Study. J Clin Oncol. 2017 Jun 1;35(16):1795-1802. doi: 10.1200/JCO.2016.69.3531. Epub 2017 Mar 29.

  PMID: 28355115 BACKGROUND

• Kuchimanchi M, Zhu M, Clements JD, Doshi S. Exposure-response analysis of blinatumomab in patients with relapsed/refractory acute lymphoblastic leukaemia and comparison with standard of care chemotherapy. Br J Clin Pharmacol. 2019 Apr;85(4):807-817. doi: 10.1111/bcp.13864. Epub 2019 Feb 18.

  PMID: 30645768 BACKGROUND

• Kantarjian HM, Zugmaier G, Bruggemann M, Wood BL, Horst HA, Zeng Y, Martinelli G. Impact of Blinatumomab Treatment on Bone Marrow Function in Patients with Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia. Cancers (Basel). 2021 Nov 9;13(22):5607. doi: 10.3390/cancers13225607.

  PMID: 34830762 BACKGROUND

• Clements JD, Zhu M, Kuchimanchi M, Terminello B, Doshi S. Population Pharmacokinetics of Blinatumomab in Pediatric and Adult Patients with Hematological Malignancies. Clin Pharmacokinet. 2020 Apr;59(4):463-474. doi: 10.1007/s40262-019-00823-8.

  PMID: 31679130 BACKGROUND

• Martinelli G, Boissel N, Chevallier P, Ottmann O, Gokbuget N, Rambaldi A, Ritchie EK, Papayannidis C, Tuglus CA, Morris JD, Stein A. Long-term follow-up of blinatumomab in patients with relapsed/refractory Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukaemia: Final analysis of ALCANTARA study. Eur J Cancer. 2021 Mar;146:107-114. doi: 10.1016/j.ejca.2020.12.022. Epub 2021 Feb 13.

  PMID: 33588145 BACKGROUND

• Topp MS, Stein AS, Gokbuget N, Horst HA, Boissel N, Martinelli G, Kantarjian H, Bruggemann M, Chen Y, Zugmaier G. Blinatumomab as first salvage versus second or later salvage in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia: Results of a pooled analysis. Cancer Med. 2021 Apr;10(8):2601-2610. doi: 10.1002/cam4.3731. Epub 2021 Mar 18.

  PMID: 33734596 BACKGROUND

• Horst HA, Zugmaier G, Martinelli G, Mergen N, Velasco K, Zaman F, Kantarjian H. CD19-negative relapse in adult patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia following treatment with blinatumomab-a post hoc analysis. Am J Hematol. 2023 Aug;98(8):E222-E225. doi: 10.1002/ajh.26988. Epub 2023 Jun 22. No abstract available.

  PMID: 37345570 BACKGROUND

• Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.

  PMID: 35622074 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Recurrence; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia

Interventions

blinatumomab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2013
• First Posted: December 4, 2013
• Study Start: January 3, 2014
• Primary Completion: May 20, 2015
• Study Completion: January 6, 2017
• Last Updated: May 28, 2024
• Results First Posted: August 9, 2017

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (8); GB (2); IT (5); DE (4); FR (3)