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

NCT03797261 | Terminated Phase 1 FDA Drug

• 2 other identifiers: M16-7852018-003314-41
• Study Type: interventional
• Target: 9
• Locations: 3 countries
• Sites: 17

Brief Summary

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.

Conditions

Acute Myeloid Leukemia; Non-Hodgkin's Lymphoma; Diffuse Large B-cell Lymphoma

Keywords

Acute Myeloid Leukemia; Non-Hodgkin's Lymphoma; Cancer; Venetoclax; AMG 176; diffuse large B-cell lymphoma (DLBCL)

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (10)

• Composite Complete Remission Rate (CRc) for Participants with AML

  Up to approximately 2 years from last subject first dose

• Objective Response Rate (ORR) for Participants with AML

  Up to approximately 2 years from last subject first dose

• ORR for Participants with NHL

  Up to approximately 2 years from last subject first dose

• Maximum 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

  Up to approximately 28 days after first dose of study drug

Study Arms (1)

Venetoclax + AMG 176

EXPERIMENTAL

Venetoclax and AMG 176 will be administered in combination. Different combinations of dose levels for venetoclax and AMG 176 will be explored.

Drug: Venetoclax; Drug: AMG 176

Interventions

Venetoclax DRUG

tablet, oral

Also known as: ABT-199

Venetoclax + AMG 176

AMG 176 DRUG

solution, intravenous

Venetoclax + AMG 176

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead
• Genentech, Inc.: collaborator
• Amgen: collaborator

Study Sites (17)

City of Hope /ID# 207393

Duarte, California, 91010, United States

Location

USC Norris Cancer Center /ID# 207396

Los Angeles, California, 90033, United States

Location

University of Iowa Hospitals and Clinics /ID# 207459

Iowa City, Iowa, 52242, United States

Location

Univ Kansas Med Ctr /ID# 207480

Kansas City, Kansas, 66160, United States

Location

Duplicate_Dana-Farber Cancer Institute /ID# 207367

Boston, Massachusetts, 02215, United States

Location

Washington University-School of Medicine /ID# 206995

St Louis, Missouri, 63110, United States

Location

NYU Langone Medical Center /ID# 207390

New York, New York, 10016-6402, United States

Location

Unc /Id# 207388

Chapel Hill, North Carolina, 27599, United States

Location

UPMC Hillman Cancer Ctr /ID# 208482

Pittsburgh, Pennsylvania, 15232, United States

Location

Calvary Mater Newcastle /ID# 211455

Waratah, New South Wales, 2298, Australia

Location

Royal Adelaide Hospital /ID# 210602

Adelaide, South Australia, 5000, Australia

Location

Alfred Health /ID# 210350

Melbourne, Victoria, 3004, Australia

Location

Universitaetsklinikum Frankfurt /ID# 207984

Frankfurt am Main, Hesse, 60590, Germany

Location

Universitaetsklinikum Leipzig /ID# 209824

Leipzig, Saxony, 04103, Germany

Location

Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 207987

Berlin, 13353, Germany

Location

Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 207803

Dresden, 01307, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 207788

Hamburg, 20246, Germany

Location

Related Links

• Related Info

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse; Neoplasms

Interventions

venetoclax; tapotoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2019
• First Posted: January 9, 2019
• Study Start: March 18, 2019
• Primary Completion: December 30, 2019
• Study Completion: December 30, 2019
• Last Updated: December 7, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3); US (9); DE (5)