Blinatumomab in Combination With AMG 404 for the Treatment of Adults With Relapsed or Refractory B Cell Precursor ALL

NCT04524455 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 20190177
• Study Type: interventional
• Target: 17
• Locations: 8 countries
• Sites: 17

Brief Summary

The primary objective of this phase 1b study is to evaluate the safety and tolerability of blinatumomab and AMG 404 in combination in adults with R/R B-ALL and to estimate the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AMG 404 when combined with continuous intravenous infusion (cIV) blinatumomab.

Conditions

Acute Lymphoblastic Leukemia

Keywords

Blinatumomab; AMG 404; Leukemia

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

  Investigators determined whether an adverse event (AE) qualified as a DLT per pre-specified protocol defined criteria. An AE was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment.

  Cohort 1: Up to 67 days; Cohort 2a: Up to 56 days

• Number of Participants Who Experienced Treatment-Emergent AEs (TEAEs)

  A TEAE was defined as any AE starting on or after first dose of blinatumomab or AMG 404. The investigator used clinical judgment to assess causal relationship. A serious AE (SAE) was defined as any AE that: * results in death, * immediately life-threatening, * requires in-patient hospitalization or prolongation of existing hospitalization, * results in persistent or significant disability/incapacity, * is a congenital anomaly/birth defect, and/or * other medically important serious AE. AEs of interest (EOIs) for blinatumomab included capillary leak syndrome, cytokine release syndrome, decreased immunoglobulins, elevated liver enzyme, embolic and thrombotic events, immunogenicity, infections, infusion reactions without considering duration, leukoencephalopathy, progressive multifocal leukoencephalopathy, neurologic events, neutropenia and febrile neutropenia, pancreatitis, and tumor lysis syndrome. EOIs for AMG 404 included non-infectious diarrhea and hemorrhages.

  Median (min, max) overall duration from first dose until 30 days after last dose is: 83.4 (40.2, 274.1) days

Secondary Outcomes (10)

• Percentage of Participants Who Achieved Complete Remission (CR) or CR With Partial Hematological Recovery (CRh) (CR/CRh)

  Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days

• Percentage of Participants Who Achieved CR

  Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days

• Median Duration of CR in Participants Who Achieved CR Within First 2 Cycles

  Up to approximately 274 days

• Median Duration of CR/CRh in Participants Who Achieved CR/CRh Within First 2 Cycles

  Up to approximately 274 days

• Steady-state Concentrations (Css) of Blinatumomab

  Cohort 1: C1D1 and D8 (predose, 2 to 24 h postdose), and D11, D18 and D29; C2D1 (predose, 2 to 24 h postdose) and D29. Cohort 2a: C1D3 and D10 (predose, 2 to 48 h postdose), and D29, D30 and D31; C2D1 (predose, 2 to 24 h postdose), D13 and D29

Study Arms (1)

Blinatumomab and AMG 404

EXPERIMENTAL

Drug: Blinatumomab; Drug: AMG 404; Drug: Dexamethasone Premedication

Interventions

Blinatumomab DRUG

Blinatumomab will be administered as a continuous intravenous infusion (cIV).

Also known as: Blincyto

Blinatumomab and AMG 404

AMG 404 DRUG

AMG 404 will be administered as an intravenous infusion (IV).

Blinatumomab and AMG 404

Dexamethasone Premedication DRUG

Dexamethasone will be administered orally or intravenously prior to blinatumomab treatment, as needed.

Blinatumomab and AMG 404

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years at enrollment.
• Greater than or equal to 5% blasts in the bone marrow.
• Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2.
• Negative pregnancy test in women of childbearing potential.

You may not qualify if:

• Cancer chemotherapy (radiotherapy, chemotherapy, antibody therapy, molecular targeted therapy) within 14 days prior to study Day 1.
• Known hypersensitivity to blinatumomab or AMG 404 or to any component of the product formulation.

Sponsors & Collaborators

• Amgen: lead

Study Sites (19)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Ordensklinikum Linz Elisabethinen

Linz, 4020, Austria

Location

Hôpital Saint Louis

Paris, 75010, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69645, France

Location

Klinikum und Fachbereich Medizin Johann Wolfgang Goethe-Universität Frankfurt am Main

Frankfurt am Main, 60590, Germany

Location

Universitätsklinikum Schleswig-Holstein

Kiel, 24105, Germany

Location

Universitaetsklinikum Regensburg

Regensburg, 93053, Germany

Location

Azienda Ospedaliera Universitaria di Bologna Policlinico S Orsola Malpighi

Bologna, 40138, Italy

Location

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

Hospital Universitari Germans Trias i Pujol

Badalona, Catalonia, 08916, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, Catalonia, 08036, Spain

Location

University College London

London, NW3 2PF, United Kingdom

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia

Interventions

blinatumomab

Condition Hierarchy (Ancestors)

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.

medinfo@amgen.com

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

Study Record Dates

• First Submitted: August 20, 2020
• First Posted: August 24, 2020
• Study Start: October 2, 2020
• Primary Completion: January 24, 2023
• Study Completion: January 24, 2023
• Last Updated: April 8, 2024
• Results First Posted: April 8, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

DE (3); ES (2); AU (1); NL (1); US (5); GB (1); IT (2); FR (2)