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

Sponsor

AbbVie (Industry)

Overall Status

Terminated

CT.gov ID

NCT03797261

Collaborator

Genentech, Inc. (Industry), Amgen (Industry)

Enrollment

Locations

Arm

9.4

Actual Duration (Months)

0.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Non-Hodgkin's Lymphoma Diffuse Large B-cell Lymphoma	Drug: Venetoclax Drug: AMG 176	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

9 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 18, 2019

Actual Primary Completion Date :

Dec 30, 2019

Actual Study Completion Date :

Dec 30, 2019

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RPTD) for Venetoclax + AMG 176 [Up to 28 days after first dose of study drug in a dose-escalation phase]
The MTD and/or RPTD of venetoclax and of AMG 176 will be determined during the dose escalation phase of the study.
Number of Participants With Adverse Events [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).]
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.

Secondary Outcome Measures

Composite Complete Remission Rate (CRc) for Participants with AML [Up to approximately 2 years from last subject first dose]
CRc rate is defined as CR + CRi (CR with incomplete blood count recovery).
Objective Response Rate (ORR) for Participants with AML [Up to approximately 2 years from last subject first dose]
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
ORR for Participants with NHL [Up to approximately 2 years from last subject first dose]
ORR is defined as the percentage of participants with documented CR + PR based on Lugano criteria for NHL.
Maximum Plasma Concentration (Cmax) of Venetoclax [Up to approximately 28 days after first dose of study drug]
Maximum observed plasma concentration (Cmax) of venetoclax.
Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax [Up to approximately 28 days after first dose of study drug]
Time to maximum plasma concentration (Tmax) of Venetoclax.
AUC of Venetoclax [Up to approximately 28 days after first dose of study drug]
Area under the plasma concentration-time curve (AUC) of venetoclax.
Maximum Plasma Concentration (Cmax) of AMG 176 [Up to approximately 16 days after first dose of study drug]
Maximum observed plasma concentration (Cmax) of AMG 176
Half-life (t1/2) of AMG 176 [Approximately 16 days after first dose of study drug]
Terminal phase elimination half-life (t1/2)
AUC of AMG 176 [Approximately 16 days after first dose of study drug]
Area Under the Plasma Concentration-time Curve (AUC) of AMG 176
Clearance (CL) of AMG 176 [Approximately 16 days after first dose of study drug]
Clearance (CL) is defined the volume of plasma cleared of the drug per unit time.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope /ID# 207393	Duarte	California	United States	91010
2	USC Norris Cancer Center /ID# 207396	Los Angeles	California	United States	90033
3	University of Iowa Hospitals and Clinics /ID# 207459	Iowa City	Iowa	United States	52242
4	Univ Kansas Med Ctr /ID# 207480	Kansas City	Kansas	United States	66160
5	Duplicate_Dana-Farber Cancer Institute /ID# 207367	Boston	Massachusetts	United States	02215
6	Washington University-School of Medicine /ID# 206995	Saint Louis	Missouri	United States	63110
7	NYU Langone Medical Center /ID# 207390	New York	New York	United States	10016-6402
8	Unc /Id# 207388	Chapel Hill	North Carolina	United States	27599
9	UPMC Hillman Cancer Ctr /ID# 208482	Pittsburgh	Pennsylvania	United States	15232
10	Calvary Mater Newcastle /ID# 211455	Waratah	New South Wales	Australia	2298
11	Royal Adelaide Hospital /ID# 210602	Adelaide	South Australia	Australia	5000
12	Alfred Health /ID# 210350	Melbourne	Victoria	Australia	3004
13	Universitaetsklinikum Frankfurt /ID# 207984	Frankfurt am Main	Hessen	Germany	60590
14	Universitaetsklinikum Leipzig /ID# 209824	Leipzig	Sachsen	Germany	04103
15	Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 207987	Berlin		Germany	13353
16	Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 207803	Dresden		Germany	01307
17	Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 207788	Hamburg		Germany	20246