A Study of Venetoclax and AMG 176 in Patients With Relapsed/Refractory Hematologic Malignancies

December 3, 2021 updated by: AbbVie

Phase 1b Study of Venetoclax and AMG 176 in Patients With Relapsed/Refractory Hematologic Malignancies

This dose-escalation study evaluating the safety, pharmacokinetics and preliminary efficacy of venetoclax in combination with AMG 176 in participants with relapsed or refractory acute myeloid leukemia (AML) and participants with Non-Hodgkin's lymphoma (NHL)/diffuse large B-cell lymphoma (DLBCL).

This study will include a dose escalation phase to identify the maximum tolerated dose/recommended phase 2 dose (MTD/RPTD) of venetoclax plus AMG 176 as well as a dose expansion phase to confirm safety, explore efficacy, and confirm the suitability of the preliminary RPTD.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • 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
    • New South Wales
      • Waratah, New South Wales, Australia, 2298
        • Calvary Mater Newcastle /ID# 211455
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Royal Adelaide Hospital /ID# 210602
    • Victoria
      • Melbourne, Victoria, Australia, 3004
        • Alfred Health /ID# 210350
  • Germany
      • Berlin, Germany, 13353
        • Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 207987
      • Dresden, Germany, 01307
        • Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 207803
      • Hamburg, Germany, 20246
        • Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 207788
    • Hessen
      • Frankfurt am Main, Hessen, Germany, 60590
        • Universitaetsklinikum Frankfurt /ID# 207984
    • Sachsen
      • Leipzig, Sachsen, Germany, 04103
        • Universitaetsklinikum Leipzig /ID# 209824
  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope /ID# 207393
      • Los Angeles, California, United States, 90033
        • USC Norris Cancer Center /ID# 207396
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics /ID# 207459
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Univ Kansas Med Ctr /ID# 207480
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Duplicate_Dana-Farber Cancer Institute /ID# 207367
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University-School of Medicine /ID# 206995
    • New York
      • New York, New York, United States, 10016-6402
        • NYU Langone Medical Center /ID# 207390
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Unc /Id# 207388
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Hillman Cancer Ctr /ID# 208482

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

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adequate kidney, liver and hematology values as described in the protocol.
  • Diagnosis of relapsed or refractory (R/R) acute myeloid leukemia (AML) or R/R Non-Hodgkin's lymphoma (NHL)/diffuse large B-cell lymphoma (DLBCL) confirmed by the World Health Organization (WHO) criteria, as appropriate.
  • Meets the following disease activity criteria:
  • AML: must have received at least 1 prior therapy for AML and be ineligible for cytotoxic therapy and allogeneic stem cell transplant.
  • NHL/DLBCL: measurable disease with a bidimensional lesion measuring at least 1.5 cm; received at least 1 prior therapy for NHL with no curative treatment option as determined by the investigator and be ineligible for a stem cell transplant.

Exclusion Criteria:

  • History of clinically significant medical condition that, in the opinion of the investigator, would adversely affect participation in this study.
  • History of of any malignancy within the last 6 months except for those specified in this protocol and low-grade malignancies not requiring active treatment such as non-melanoma skin cancer, cervical intraepithelial neoplasia, or prostate cancer in situ.
  • Prior allogeneic stem cell transplant or autologous stem cell transplant within 100 days of study drug administration and no signs or symptoms of acute or chronic graft-versus-host disease.
  • Previous enrollment in a randomized trial including either venetoclax or AMG 176.
  • Known active or chronic pancreatitis; severe chronic obstructive pulmonary disease with hypoxemia; central nervous system manifestations of malignancy.
  • Active, uncontrolled infection.

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: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Venetoclax + AMG 176
Venetoclax and AMG 176 will be administered in combination. Different combinations of dose levels for venetoclax and AMG 176 will be explored.
Drug: Venetoclax
tablet, oral
Other Names:
  • ABT-199
Drug: AMG 176
solution, intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RPTD) for Venetoclax + AMG 176
Time Frame: Up to 28 days after first dose of study drug in a dose-escalation phase
The MTD and/or RPTD of venetoclax and of AMG 176 will be determined during the dose escalation phase of the study.
Up to 28 days after first dose of study drug in a dose-escalation phase
Number of Participants With Adverse Events
Time Frame: From first dose of study drug until 30 days or 5 half-lives after discontinuation of study drug administration will be collected (up to approximately 4 years).
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
From first dose of study drug until 30 days or 5 half-lives after discontinuation of study drug administration will be collected (up to approximately 4 years).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite Complete Remission Rate (CRc) for Participants with AML
Time Frame: Up to approximately 2 years from last subject first dose
CRc rate is defined as CR + CRi (CR with incomplete blood count recovery).
Up to approximately 2 years from last subject first dose
Objective Response Rate (ORR) for Participants with AML
Time Frame: Up to approximately 2 years from last subject first dose
ORR is defined as the percentage of participants with documented partial response (PR) or better (CR + CRi + partial response [PR]) based on International Working Group (IWG) criteria for AML
Up to approximately 2 years from last subject first dose
ORR for Participants with NHL
Time Frame: Up to approximately 2 years from last subject first dose
ORR is defined as the percentage of participants with documented CR + PR based on Lugano criteria for NHL.
Up to approximately 2 years from last subject first dose
Maximum Plasma Concentration (Cmax) of Venetoclax
Time Frame: Up to approximately 28 days after first dose of study drug
Maximum observed plasma concentration (Cmax) of venetoclax.
Up to approximately 28 days after first dose of study drug
Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax
Time Frame: Up to approximately 28 days after first dose of study drug
Time to maximum plasma concentration (Tmax) of Venetoclax.
Up to approximately 28 days after first dose of study drug
AUC of Venetoclax
Time Frame: Up to approximately 28 days after first dose of study drug
Area under the plasma concentration-time curve (AUC) of venetoclax.
Up to approximately 28 days after first dose of study drug
Maximum Plasma Concentration (Cmax) of AMG 176
Time Frame: Up to approximately 16 days after first dose of study drug
Maximum observed plasma concentration (Cmax) of AMG 176
Up to approximately 16 days after first dose of study drug
Half-life (t1/2) of AMG 176
Time Frame: Approximately 16 days after first dose of study drug
Terminal phase elimination half-life (t1/2)
Approximately 16 days after first dose of study drug
AUC of AMG 176
Time Frame: Approximately 16 days after first dose of study drug
Area Under the Plasma Concentration-time Curve (AUC) of AMG 176
Approximately 16 days after first dose of study drug
Clearance (CL) of AMG 176
Time Frame: Approximately 16 days after first dose of study drug
Clearance (CL) is defined the volume of plasma cleared of the drug per unit time.
Approximately 16 days after first dose of study drug

Collaborators and Investigators

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

Sponsor

AbbVie

Collaborators

Genentech, Inc.
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)

March 18, 2019

Primary Completion (Actual)

December 30, 2019

Study Completion (Actual)

December 30, 2019

Study Registration Dates

First Submitted

January 7, 2019

First Submitted That Met QC Criteria

January 7, 2019

First Posted (Actual)

January 9, 2019

Study Record Updates

Last Update Posted (Actual)

December 7, 2021

Last Update Submitted That Met QC Criteria

December 3, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M16-785
  • 2018-003314-41 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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