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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03797261
Recruitment Status : Suspended (Suspended to evaluate safety)
First Posted : January 9, 2019
Last Update Posted : October 1, 2019
Sponsor:
Collaborators:
Genentech, Inc.
Amgen
Information provided by (Responsible Party):
AbbVie

Study Description
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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
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 86 participants
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 : March 15, 2019
Estimated Primary Completion Date : September 2, 2022
Estimated Study Completion Date : September 2, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Venetoclax

Arms and Interventions
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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 Name: ABT-199

Drug: AMG 176
solution, intravenous


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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).

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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)

  9. 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

  10. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03797261


Locations
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Sponsors and Collaborators
AbbVie
Genentech, Inc.
Amgen
Investigators
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Study Director: AbbVie Inc. AbbVie
More Information
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Additional Information:

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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03797261    
Other Study ID Numbers: M16-785
2018-003314-41 ( EudraCT Number )
First Posted: January 9, 2019    Key Record Dates
Last Update Posted: October 1, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by AbbVie:
Acute Myeloid Leukemia
Non-Hodgkin's Lymphoma
Cancer
 Venetoclax
AMG 176
diffuse large B-cell lymphoma (DLBCL)
Additional relevant MeSH terms:
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Lymphoma
Leukemia, Myeloid, Acute
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
 Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia
Leukemia, Myeloid
Neoplasms by Site
Hematologic Diseases
Venetoclax
Antineoplastic Agents