A Study of Venetoclax and AMG 176 in Patients With Relapsed/Refractory Hematologic Malignancies
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ClinicalTrials.gov Identifier: NCT03797261 |
Recruitment Status :
Suspended
(Safety)
First Posted : January 9, 2019
Last Update Posted : December 17, 2020
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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 Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 86 participants |
Allocation: | N/A |
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 18, 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.
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Drug: Venetoclax
tablet, oral
Other Name: ABT-199 Drug: AMG 176 solution, intravenous |
- 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.
- 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.

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

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

Study Director: | AbbVie Inc. | AbbVie |
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: | December 17, 2020 |
Last Verified: | December 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
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 |
Acute Myeloid Leukemia Non-Hodgkin's Lymphoma Cancer |
Venetoclax AMG 176 diffuse large B-cell lymphoma (DLBCL) |
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 |