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

Phase 1TerminatedNCT03797261

AbbVie9 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

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

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (17)

City of Hope /ID# 207393

Duarte, California, United States

USC Norris Cancer Center /ID# 207396

Los Angeles, California, United States

University of Iowa Hospitals and Clinics /ID# 207459

Iowa City, Iowa, United States

Univ Kansas Med Ctr /ID# 207480

Kansas City, Kansas, United States

Duplicate_Dana-Farber Cancer Institute /ID# 207367

Boston, Massachusetts, United States

Washington University-School of Medicine /ID# 206995

St Louis, Missouri, United States

NYU Langone Medical Center /ID# 207390

New York, New York, United States

Unc /Id# 207388

Chapel Hill, North Carolina, United States

UPMC Hillman Cancer Ctr /ID# 208482

Pittsburgh, Pennsylvania, United States

Calvary Mater Newcastle /ID# 211455

Waratah, New South Wales, Australia

...and 7 more locations

Outcomes

Primary Outcomes

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.

Time frame: 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.

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).

Secondary Outcomes

Composite Complete Remission Rate (CRc) for Participants with AML

CRc rate is defined as CR + CRi (CR with incomplete blood count recovery).

Time frame: 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

Time frame: 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.

Time frame: Up to approximately 2 years from last subject first dose

Maximum Plasma Concentration (Cmax) of Venetoclax

Maximum observed plasma concentration (Cmax) of venetoclax.

Time frame: 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.

Time frame: Up to approximately 28 days after first dose of study drug

AUC of Venetoclax

Area under the plasma concentration-time curve (AUC) of venetoclax.

Time frame: 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

Time frame: 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)

Time frame: Approximately 16 days after first dose of study drug

AUC of AMG 176

Area Under the Plasma Concentration-time Curve (AUC) of AMG 176

Time frame: 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.

Time frame: Approximately 16 days after first dose of study drug