search
Back to results

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

Primary Purpose

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

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Venetoclax
AMG 176
Sponsored by
AbbVie
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute Myeloid Leukemia, Non-Hodgkin's Lymphoma, Cancer, Venetoclax, AMG 176, diffuse large B-cell lymphoma (DLBCL)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • City of Hope /ID# 207393
  • USC Norris Cancer Center /ID# 207396
  • University of Iowa Hospitals and Clinics /ID# 207459
  • Univ Kansas Med Ctr /ID# 207480
  • Duplicate_Dana-Farber Cancer Institute /ID# 207367
  • Washington University-School of Medicine /ID# 206995
  • NYU Langone Medical Center /ID# 207390
  • Unc /Id# 207388
  • UPMC Hillman Cancer Ctr /ID# 208482
  • Calvary Mater Newcastle /ID# 211455
  • Royal Adelaide Hospital /ID# 210602
  • Alfred Health /ID# 210350
  • Universitaetsklinikum Frankfurt /ID# 207984
  • Universitaetsklinikum Leipzig /ID# 209824
  • Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 207987
  • Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 207803
  • Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 207788

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Venetoclax + AMG 176

Arm Description

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

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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

Full Information

First Posted
January 7, 2019
Last Updated
December 3, 2021
Sponsor
AbbVie
Collaborators
Genentech, Inc., Amgen
search

1. Study Identification

Unique Protocol Identification Number
NCT03797261
Brief Title
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

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Terminated
Why Stopped
Safety
Study Start Date
March 18, 2019 (Actual)
Primary Completion Date
December 30, 2019 (Actual)
Study Completion Date
December 30, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
Collaborators
Genentech, Inc., Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Venetoclax + AMG 176
Arm Type
Experimental
Arm Description
Venetoclax and AMG 176 will be administered in combination. Different combinations of dose levels for venetoclax and AMG 176 will be explored.
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
ABT-199
Intervention Description
tablet, oral
Intervention Type
Drug
Intervention Name(s)
AMG 176
Intervention Description
solution, intravenous
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RPTD) for Venetoclax + AMG 176
Description
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
Title
Number of Participants With Adverse Events
Description
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 Outcome Measure Information:
Title
Composite Complete Remission Rate (CRc) for Participants with AML
Description
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
Title
Objective Response Rate (ORR) for Participants with AML
Description
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
Title
ORR for Participants with NHL
Description
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
Title
Maximum Plasma Concentration (Cmax) of Venetoclax
Description
Maximum observed plasma concentration (Cmax) of venetoclax.
Time Frame
Up to approximately 28 days after first dose of study drug
Title
Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax
Description
Time to maximum plasma concentration (Tmax) of Venetoclax.
Time Frame
Up to approximately 28 days after first dose of study drug
Title
AUC of Venetoclax
Description
Area under the plasma concentration-time curve (AUC) of venetoclax.
Time Frame
Up to approximately 28 days after first dose of study drug
Title
Maximum Plasma Concentration (Cmax) of AMG 176
Description
Maximum observed plasma concentration (Cmax) of AMG 176
Time Frame
Up to approximately 16 days after first dose of study drug
Title
Half-life (t1/2) of AMG 176
Description
Terminal phase elimination half-life (t1/2)
Time Frame
Approximately 16 days after first dose of study drug
Title
AUC of AMG 176
Description
Area Under the Plasma Concentration-time Curve (AUC) of AMG 176
Time Frame
Approximately 16 days after first dose of study drug
Title
Clearance (CL) of AMG 176
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ABBVIE INC.
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope /ID# 207393
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
USC Norris Cancer Center /ID# 207396
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
University of Iowa Hospitals and Clinics /ID# 207459
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Univ Kansas Med Ctr /ID# 207480
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Duplicate_Dana-Farber Cancer Institute /ID# 207367
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Washington University-School of Medicine /ID# 206995
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
NYU Langone Medical Center /ID# 207390
City
New York
State/Province
New York
ZIP/Postal Code
10016-6402
Country
United States
Facility Name
Unc /Id# 207388
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
UPMC Hillman Cancer Ctr /ID# 208482
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Calvary Mater Newcastle /ID# 211455
City
Waratah
State/Province
New South Wales
ZIP/Postal Code
2298
Country
Australia
Facility Name
Royal Adelaide Hospital /ID# 210602
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Alfred Health /ID# 210350
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Universitaetsklinikum Frankfurt /ID# 207984
City
Frankfurt am Main
State/Province
Hessen
ZIP/Postal Code
60590
Country
Germany
Facility Name
Universitaetsklinikum Leipzig /ID# 209824
City
Leipzig
State/Province
Sachsen
ZIP/Postal Code
04103
Country
Germany
Facility Name
Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 207987
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 207803
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 207788
City
Hamburg
ZIP/Postal Code
20246
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.rxabbvie.com
Description
Related Info

Learn more about this trial

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

We'll reach out to this number within 24 hrs