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

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: Acute Myeloid Leukemia; Non-Hodgkin's Lymphoma; Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Drug: Venetoclax; Drug: AMG 176

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

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

Eligibility Criteria

• Ages Eligible for Study: 14 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

How is the study designed?

Design Details

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

Number of Arms

1

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	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	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	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	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	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	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 to maximum plasma concentration (Tmax) of Venetoclax.	Up to approximately 28 days after first dose of study drug
AUC of Venetoclax	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	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	Terminal phase elimination half-life (t1/2)	Approximately 16 days after first dose of study drug
AUC of AMG 176	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	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

• Sponsor: AbbVie
• Collaborators: Genentech, Inc.; Amgen

Publications and helpful links

Helpful Links

• Related Info

Study record dates

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: Cancer; Acute Myeloid Leukemia; Venetoclax; Non-Hodgkin's Lymphoma; AMG 176; diffuse large B-cell lymphoma (DLBCL)
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Hematologic Diseases; Leukemia; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Hematologic Neoplasms; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Antineoplastic Agents; Venetoclax
• 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