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

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ClinicalTrials.gov Identifier: NCT03797261
Recruitment Status : Recruiting
First Posted : January 9, 2019
Last Update Posted : August 28, 2019
Sponsor:
Collaborators:
Genentech, Inc.
Amgen
Information provided by (Responsible Party):
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.


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

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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


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




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.



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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.

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


Contacts
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Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com

Locations
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United States, California
City of Hope /ID# 207393 Recruiting
Duarte, California, United States, 91010
USC Norris Cancer Center /ID# 207396 Not yet recruiting
Los Angeles, California, United States, 90033
United States, Florida
Miami Cancer Institute - Baptist Health South Florida /ID# 209825 Not yet recruiting
Miami, Florida, United States, 33176
United States, Iowa
University of Iowa Hospitals and Clinics /ID# 207459 Recruiting
Iowa City, Iowa, United States, 52242
United States, Kansas
Univ Kansas Med Ctr /ID# 207480 Recruiting
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Dana-Farber Cancer Institute /ID# 207367 Recruiting
Boston, Massachusetts, United States, 02215
United States, Missouri
Washington University-School of Medicine /ID# 206995 Recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
NYU Langone Medical Center /ID# 207390 Recruiting
New York, New York, United States, 10016-6402
United States, North Carolina
Unc /Id# 207388 Not yet recruiting
Chapel Hill, North Carolina, United States, 27599
United States, Pennsylvania
UPMC Hillman Cancer Ctr /ID# 208482 Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Australia, New South Wales
Calvary Mater Newcastle /ID# 211455 Not yet recruiting
Waratah, New South Wales, Australia, 2298
Australia, South Australia
Royal Adelaide Hospital /ID# 210602 Not yet recruiting
Adelaide, South Australia, Australia, 5000
Australia, Victoria
St. Vincents Hosp Melbourne /ID# 210601 Not yet recruiting
Fitzroy, Victoria, Australia, 3065
Alfred Hospital /ID# 210350 Recruiting
Melbourne, Victoria, Australia, 3004
Box Hill Hospital /ID# 210599 Not yet recruiting
Melbourne, Victoria, Australia, 3128
Germany
Universitaetsklinikum Leipzig /ID# 209824 Not yet recruiting
Leipzig, Sachsen, Germany, 04103
Charite Universitatsmedizin B- /ID# 207987 Not yet recruiting
Berlin, Germany, 13353
Universitaetklinikum Dresden /ID# 207803 Not yet recruiting
Dresden, Germany, 01307
Universitaetsklinikum Frankfurt /ID# 207984 Not yet recruiting
Frankfurt, Germany, 60590
Univ Klinik Eppendorf Hamburg /ID# 207788 Not yet recruiting
Hamburg, Germany, 20246
Sponsors and Collaborators
AbbVie
Genentech, Inc.
Amgen
Investigators
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Study Director: AbbVie Inc. AbbVie

Additional Information:
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03797261     History of Changes
Other Study ID Numbers: M16-785
First Posted: January 9, 2019    Key Record Dates
Last Update Posted: August 28, 2019
Last Verified: August 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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Leukemia, Myeloid, Acute
Leukemia
Leukemia, Myeloid
Venetoclax
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents