A Study of Venetoclax and AMG 176 in Patients With Relapsed/Refractory Hematologic Malignancies
- Conditions
- Acute Myeloid LeukemiaNon-Hodgkin's LymphomaDiffuse Large B-cell Lymphoma
- Interventions
- Registration Number
- NCT03797261
- Lead Sponsor
- AbbVie
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 9
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Venetoclax + AMG 176 Venetoclax Venetoclax and AMG 176 will be administered in combination. Different combinations of dose levels for venetoclax and AMG 176 will be explored. Venetoclax + AMG 176 AMG 176 Venetoclax and AMG 176 will be administered in combination. Different combinations of dose levels for venetoclax and AMG 176 will be explored.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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.
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 Venetoclax Up to approximately 28 days after first dose of study drug Area under the plasma concentration-time curve (AUC) 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.
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
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.
Trial Locations
- Locations (17)
USC Norris Cancer Center /ID# 207396
🇺🇸Los Angeles, California, United States
Duplicate_Dana-Farber Cancer Institute /ID# 207367
🇺🇸Boston, Massachusetts, United States
Calvary Mater Newcastle /ID# 211455
🇦🇺Waratah, New South Wales, Australia
Royal Adelaide Hospital /ID# 210602
🇦🇺Adelaide, South Australia, Australia
Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 207987
🇩🇪Berlin, Germany
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
Washington University-School of Medicine /ID# 206995
🇺🇸Saint Louis, Missouri, United States
NYU Langone Medical Center /ID# 207390
🇺🇸New York, New York, United States
UPMC Hillman Cancer Ctr /ID# 208482
🇺🇸Pittsburgh, Pennsylvania, United States
Alfred Health /ID# 210350
🇦🇺Melbourne, Victoria, Australia
Universitaetsklinikum Frankfurt /ID# 207984
🇩🇪Frankfurt am Main, Hessen, Germany
Universitaetsklinikum Leipzig /ID# 209824
🇩🇪Leipzig, Sachsen, Germany
Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 207803
🇩🇪Dresden, Germany
Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 207788
🇩🇪Hamburg, Germany