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

October 11, 2023 updated by: Amgen

A Phase 1b Open-label Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Administration of Blinatumomab in Combination With AMG 404 for the Treatment of Adults With Relapsed or Refractory B Cell Precursor Acute Lymphoblastic Leukemia (ALL)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
17

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Royal Adelaide Hospital
    • Victoria
      • Parkville, Victoria, Australia, 3050
        • The Royal Melbourne Hospital
  • Austria
      • Linz, Austria, 4020
        • Ordensklinikum Linz Elisabethinen
  • France
      • Paris, France, 75010
        • Hopital Saint Louis
      • Pierre Benite, France, 69645
        • Centre Hospitalier Lyon Sud
  • Germany
      • Frankfurt am Main, Germany, 60590
        • Klinikum und Fachbereich Medizin Johann Wolfgang Goethe-Universität Frankfurt am Main
      • Kiel, Germany, 24105
        • Universitätsklinikum Schleswig-Holstein
      • Regensburg, Germany, 93053
        • Universitaetsklinikum Regensburg
  • Italy
      • Bologna, Italy, 40138
        • Azienda Ospedaliera Universitaria di Bologna Policlinico S Orsola Malpighi
      • Brescia, Italy, 25123
        • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
  • Netherlands
      • Groningen, Netherlands, 9713 GZ
        • Universitair Medisch Centrum Groningen
  • Spain
    • Cataluña
      • Badalona, Cataluña, Spain, 08916
        • Hospital Universitari Germans Trias i Pujol
      • Barcelona, Cataluña, Spain, 08036
        • Hospital Clinic i Provincial de Barcelona
  • United Kingdom
      • London, United Kingdom, NW3 2PF
        • University College London
  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
    • New York
      • New York, New York, United States, 10029
        • Icahn School of Medicine at Mount Sinai
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Taussig Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  • 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.

Exclusion Criteria

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Blinatumomab and AMG 404
Drug: Blinatumomab
Blinatumomab will be administered as a continuous intravenous infusion (cIV).
Other Names:
  • Blincyto
Drug: AMG 404
AMG 404 will be administered as an intravenous infusion (IV).
Drug: Dexamethasone Premedication
Dexamethasone will be administered orally or intravenously prior to blinatumomab treatment, as needed.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Time Frame: Cohort 1: Up to 67 days; Cohort 2a: Up to 56 days
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)
Time Frame: Median (min, max) overall duration from first dose until 30 days after last dose is: 83.4 (40.2, 274.1) days

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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Achieved Complete Remission (CR) or CR With Partial Hematological Recovery (CRh) (CR/CRh)
Time Frame: Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days

Hematological remissions were defined by the following criteria:

CR:

  • Less than 5% blasts in the bone marrow (BM)
  • No evidence of disease
  • Full recovery of peripheral blood (PB) counts:
  • Platelets > 100 000/μl
  • Absolute neutrophil count (ANC) > 1000/μl

CR with only CRh:

  • Less than 5% blasts in the BM
  • No evidence of disease
  • Partial recovery of PB counts:
  • Platelets > 50 000/μl and
  • ANC > 500/μl

Percentage of participants with CR/CRh were summarized along with corresponding 95% exact confidence interval (CI) using the Clopper-Pearson method.
Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days
Percentage of Participants Who Achieved CR
Time Frame: Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days

Hematological remissions were defined by the following criteria:

CR:

  • Less than 5% blasts in the BM
  • No evidence of disease
  • Full recovery of PB counts:
  • Platelets > 100 000/μl
  • ANC > 1000/μl

Percentage of participants with CR were summarized along with corresponding 95% exact CI using the Clopper-Pearson method.
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
Time Frame: Up to approximately 274 days

Duration of CR was calculated from the date CR was first achieved within the first 2 cycles until the earliest date of disease assessment indicating a relapse event or death due to any cause, whichever occurred first. Months were calculated as days from date of CR to event/censor date, divided by 30.5.

Median time to event and 95% CI was summarized using the Kaplan-Meier (KM) method.
Up to approximately 274 days
Median Duration of CR/CRh in Participants Who Achieved CR/CRh Within First 2 Cycles
Time Frame: Up to approximately 274 days

Duration of CR/CRh was calculated from the date CR/CRh was first achieved within the first 2 cycles until the earliest date of disease assessment indicating a relapse event or death due to any cause, whichever occurred first. Months were calculated as days from date of CR/CRh to event/censor date, divided by 30.5.

Median time to event and 95% CI was summarized using the KM method.
Up to approximately 274 days
Steady-state Concentrations (Css) of Blinatumomab
Time Frame: 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
Pharmacokinetic (PK) parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.
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
Maximum Observed Concentration (Cmax) of AMG 404
Time Frame: Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion)
PK parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.
Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion)
Time to Cmax (Tmax) of AMG 404
Time Frame: Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion)
PK parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.
Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion)
Area Under the Plasma Concentration-time Curve From Time 0 to 28 Days Post Infusion (AUC0-28d) of AMG 404
Time Frame: Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion)
PK parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.
Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion)
Number of Participants With Incidences of Anti-Blinatumomab Antibodies
Time Frame: Up to approximately 274 days
Only samples testing positive for anti-blinatumomab binding antibodies were to be tested for neutralizing antibodies (NAbs) as pre-specified in the protocol.
Up to approximately 274 days
Number of Participants With Incidences of Anti-AMG 404 Antibodies
Time Frame: Up to approximately 274 days
Only samples testing positive for anti-AMG 404 binding antibodies were to be tested for NAbs as pre-specified in the protocol.
Up to approximately 274 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Amgen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: MD, Amgen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 2, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 24, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 24, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 20, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 20, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 24, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 8, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 11, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 20190177

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

IPD Sharing 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.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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