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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03797261
• Other study ID #: M16-785
• Secondary ID: 2018-003314-41
• Status: Terminated
• Phase: Phase 1
• Start date: March 18, 2019
• Est. completion date: December 30, 2019

Study information

• Verified date: December 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: December 30, 2019
• Est. primary completion date: December 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Diffuse Large B-cell Lymphoma
• Hematologic Neoplasms
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma

Intervention

Drug:
• Venetoclax
tablet, oral
• AMG 176
solution, intravenous

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital /ID# 210602	Adelaide	South Australia
Australia	Alfred Health /ID# 210350	Melbourne	Victoria
Australia	Calvary Mater Newcastle /ID# 211455	Waratah	New South Wales
Germany	Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 207987	Berlin
Germany	Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 207803	Dresden
Germany	Universitaetsklinikum Frankfurt /ID# 207984	Frankfurt am Main	Hessen
Germany	Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 207788	Hamburg
Germany	Universitaetsklinikum Leipzig /ID# 209824	Leipzig	Sachsen
United States	Duplicate_Dana-Farber Cancer Institute /ID# 207367	Boston	Massachusetts
United States	Unc /Id# 207388	Chapel Hill	North Carolina
United States	City of Hope /ID# 207393	Duarte	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	USC Norris Cancer Center /ID# 207396	Los Angeles	California
United States	NYU Langone Medical Center /ID# 207390	New York	New York
United States	UPMC Hillman Cancer Ctr /ID# 208482	Pittsburgh	Pennsylvania
United States	Washington University-School of Medicine /ID# 206995	Saint Louis	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
AbbVie	Amgen, Genentech, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	Maximum Plasma Concentration (Cmax) of Venetoclax	Maximum observed plasma concentration (Cmax) of venetoclax.	Up to approximately 28 days after first dose of study drug
Secondary	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
Secondary	AUC of Venetoclax	Area under the plasma concentration-time curve (AUC) of venetoclax.	Up to approximately 28 days after first dose of study drug
Secondary	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
Secondary	Half-life (t1/2) of AMG 176	Terminal phase elimination half-life (t1/2)	Approximately 16 days after first dose of study drug
Secondary	AUC of AMG 176	Area Under the Plasma Concentration-time Curve (AUC) of AMG 176	Approximately 16 days after first dose of study drug
Secondary	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

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