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

• ClinicalTrials.gov Identifier: NCT03797261
• Recruitment Status: Suspended
• First Posted: January 9, 2019
• Last Update Posted: October 1, 2019
• Sponsor: AbbVie
• Collaborators: Genentech, Inc.; Amgen
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: January 7, 2019
• First Posted Date: January 9, 2019
• Last Update Posted Date: October 1, 2019
• Actual Study Start Date: March 15, 2019
• Estimated Primary Completion Date: September 2, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 7, 2019)

• Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RPTD) for Venetoclax + AMG 176 [ Time Frame: 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 [ 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). ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 7, 2019)

• Composite Complete Remission Rate (CRc) for Participants with AML [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to approximately 28 days after first dose of study drug ]
  Time to maximum plasma concentration (Tmax) of Venetoclax.
• AUC of Venetoclax [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Approximately 16 days after first dose of study drug ]
  Terminal phase elimination half-life (t1/2)
• AUC of AMG 176 [ Time Frame: 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 [ Time Frame: Approximately 16 days after first dose of study drug ]
  Clearance (CL) is defined the volume of plasma cleared of the drug per unit time.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

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 Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

• Drug: Venetoclax
  tablet, oral
  Other Name: ABT-199
• Drug: AMG 176
  solution, intravenous

Study Arms

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.

Interventions:

• Drug: Venetoclax
• Drug: AMG 176

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Suspended
• Estimated Enrollment (submitted: January 7, 2019): 86
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2, 2022
• Estimated Primary Completion Date: September 2, 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Germany, United States

Administrative Information

• NCT Number: NCT03797261
• Other Study ID Numbers: M16-785; 2018-003314-41 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: AbbVie
• Study Sponsor: AbbVie

Collaborators

• Genentech, Inc.
• Amgen

Investigators

• Study Director: AbbVie Inc.; AbbVie

• PRS Account: AbbVie
• Verification Date: September 2019