Clinical trial NCT03797261: A Study of Venetoclax and AMG 176 in Patients With Relapsed/Refractory Hematologic Malignancies
Official title: Phase 1b Study of Venetoclax and AMG 176 in Patients With Relapsed/Refractory Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
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)
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Genentech, Inc.
name: Amgen
First posted: 2019-01-09
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RPTD) for Venetoclax + AMG 176
timeFrame: Up to 28 days after first dose of study drug in a dose-escalation phase
measure: Number of Participants With Adverse Events
timeFrame: 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:
measure: Composite Complete Remission Rate (CRc) for Participants with AML
timeFrame: Up to approximately 2 years from last subject first dose
measure: Objective Response Rate (ORR) for Participants with AML
timeFrame: Up to approximately 2 years from last subject first dose
measure: ORR for Participants with NHL
timeFrame: Up to approximately 2 years from last subject first dose
measure: Maximum Plasma Concentration (Cmax) of Venetoclax
timeFrame: Up to approximately 28 days after first dose of study drug
measure: Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax
timeFrame: Up to approximately 28 days after first dose of study drug
measure: AUC of Venetoclax
timeFrame: Up to approximately 28 days after first dose of study drug
measure: Maximum Plasma Concentration (Cmax) of AMG 176
timeFrame: Up to approximately 16 days after first dose of study drug
measure: Half-life (t1/2) of AMG 176
timeFrame: Approximately 16 days after first dose of study drug
measure: AUC of AMG 176
timeFrame: Approximately 16 days after first dose of study drug
measure: Clearance (CL) of AMG 176
timeFrame: Approximately 16 days after first dose of study drug
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope /ID# 207393
state: California
city: Los Angeles
country: United States
facility: USC Norris Cancer Center /ID# 207396
state: California
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics /ID# 207459
state: Iowa
city: Kansas City
country: United States
facility: Univ Kansas Med Ctr /ID# 207480
state: Kansas
city: Boston
country: United States
facility: Duplicate_Dana-Farber Cancer Institute /ID# 207367
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University-School of Medicine /ID# 206995
state: Missouri
city: New York
country: United States
facility: NYU Langone Medical Center /ID# 207390
state: New York
city: Chapel Hill
country: United States
facility: Unc /Id# 207388
state: North Carolina
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Ctr /ID# 208482
state: Pennsylvania
city: Waratah
country: Australia
facility: Calvary Mater Newcastle /ID# 211455
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital /ID# 210602
state: South Australia
city: Melbourne
country: Australia
facility: Alfred Health /ID# 210350
state: Victoria
city: Frankfurt am Main
country: Germany
facility: Universitaetsklinikum Frankfurt /ID# 207984
state: Hessen
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig /ID# 209824
state: Sachsen
city: Berlin
country: Germany
facility: Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 207987
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 207803
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 207788
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: