Acute Myeloid LeukemiaPhase 1NCT03797261
A Study of Venetoclax and AMG 176 in Patients With Relapsed/Refractory Hematologic Malignancies
A Phase 1 study testing Venetoclax and AMG 176 in people with Acute Myeloid Leukemia and Non-Hodgkin's Lymphoma, run by AbbVie at 17 sites in 3 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Non-Hodgkin's Lymphoma, Diffuse Large B-cell Lymphoma
- What is being tested?
- Venetoclax and AMG 176
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 17 sitesin 3 countries
- Study dates
- 18 Mar 2019to 30 Dec 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
17 sites in 3 countries.
17 sites in 3 countries
United States9 sites
Duplicate_Dana-Farber Cancer Institute /ID# 207367
Boston, Massachusetts, 02215
Unc /Id# 207388
Chapel Hill, North Carolina, 27599
City of Hope /ID# 207393
Duarte, California, 91010
University of Iowa Hospitals and Clinics /ID# 207459
Iowa City, Iowa, 52242
Univ Kansas Med Ctr /ID# 207480
Kansas City, Kansas, 66160
USC Norris Cancer Center /ID# 207396
Los Angeles, California, 90033
NYU Langone Medical Center /ID# 207390
New York, New York, 10016-6402
UPMC Hillman Cancer Ctr /ID# 208482
Pittsburgh, Pennsylvania, 15232
Washington University-School of Medicine /ID# 206995
St Louis, Missouri, 63110
Germany5 sites
Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 207987
Berlin, 13353
Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 207803
Dresden, 01307
Universitaetsklinikum Frankfurt /ID# 207984
Frankfurt am Main, Hesse, 60590
Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 207788
Hamburg, 20246
Universitaetsklinikum Leipzig /ID# 209824
Leipzig, Saxony, 04103
Australia3 sites
Royal Adelaide Hospital /ID# 210602
Adelaide, South Australia, 5000
Alfred Health /ID# 210350
Melbourne, Victoria, 3004
Calvary Mater Newcastle /ID# 211455
Waratah, New South Wales, 2298
About this study
Official title: Phase 1b Study of Venetoclax and AMG 176 in Patients With Relapsed/Refractory Hematologic Malignancies
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.
- Being tested
- Venetoclax, AMG 176
- Keywords
- Acute Myeloid Leukemia, Non-Hodgkin's Lymphoma, Cancer, Venetoclax, AMG 176, diffuse large B-cell lymphoma (DLBCL)
- Medical subject headings
- Leukemia, Myeloid, Acute, Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VenetoclaxDrug
Also called ABT-199
tablet, oral
AMG 176Drug
solution, intravenous
| Study group | Role | What they receive |
|---|---|---|
| Venetoclax + AMG 176 | Experimental | Venetoclax and AMG 176 will be administered in combination. Different combinations of dose levels for venetoclax and AMG 176 will be explored. Receives: Drug: Venetoclax; Drug: AMG 176 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RPTD) for Venetoclax + AMG 176
The MTD and/or RPTD of venetoclax and of AMG 176 will be determined during the dose escalation phase of the study.
Measured: Up to 28 days after first dose of study drug in a dose-escalation phase
Number of Participants With Adverse Events
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.
Measured: 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).
Secondary outcomes (10)
Composite Complete Remission Rate (CRc) for Participants with AML
CRc rate is defined as CR + CRi (CR with incomplete blood count recovery).
Measured: Up to approximately 2 years from last subject first dose
Objective Response Rate (ORR) for Participants with AML
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
Measured: Up to approximately 2 years from last subject first dose
ORR for Participants with NHL
ORR is defined as the percentage of participants with documented CR + PR based on Lugano criteria for NHL.
Measured: Up to approximately 2 years from last subject first dose
Maximum Plasma Concentration (Cmax) of Venetoclax
Maximum observed plasma concentration (Cmax) of venetoclax.
Measured: Up to approximately 28 days after first dose of study drug
Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax
Time to maximum plasma concentration (Tmax) of Venetoclax.
Measured: Up to approximately 28 days after first dose of study drug
AUC of Venetoclax
Area under the plasma concentration-time curve (AUC) of venetoclax.
Measured: Up to approximately 28 days after first dose of study drug
Maximum Plasma Concentration (Cmax) of AMG 176
Maximum observed plasma concentration (Cmax) of AMG 176
Measured: Up to approximately 16 days after first dose of study drug
Half-life (t1/2) of AMG 176
Terminal phase elimination half-life (t1/2)
Measured: Approximately 16 days after first dose of study drug
AUC of AMG 176
Area Under the Plasma Concentration-time Curve (AUC) of AMG 176
Measured: Approximately 16 days after first dose of study drug
Clearance (CL) of AMG 176
Clearance (CL) is defined the volume of plasma cleared of the drug per unit time.
Measured: Approximately 16 days after first dose of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2019
- Study start18 Mar 2019
- Primary completion30 Dec 2019
- Study completion30 Dec 2019
Why it stopped: Safety
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by AbbVieThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Genentech, Inc., Amgen
- Responsible party
- Sponsor
- Investigators
- ABBVIE INC., Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03797261
- Sponsor's protocol ID
- M16-785
- Other IDs
- 2018-003314-41, 2018
- Status last verified
- Dec 2021
- First submitted
- 7 Jan 2019
- Last updated
- 7 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1b Study of Venetoclax and AMG 176 in Patients With Relapsed/Refractory Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT03797261
- Acronym / sponsor ID
- M16-785
- Keywords
- Acute Myeloid Leukemia, Non-Hodgkin's Lymphoma, Cancer, Venetoclax, AMG 176, diffuse large B-cell lymphoma (DLBCL)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Safety
- Enrolment
- 9 participants (actual)
- Lead sponsor
- AbbVieIndustry (pharma, biotech, devices)
- Collaborators
- Genentech, Inc., Amgen
- Study start
- 18 Mar 2019 (actual)
- Primary completion
- 30 Dec 2019 (actual)
- Study completion
- 30 Dec 2019 (actual)
- First posted
- 9 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Venetoclax + AMG 176 | Experimental | Drug: Venetoclax, Drug: AMG 176Venetoclax and AMG 176 will be administered in combination. Different combinations of dose levels for venetoclax and AMG 176 will be explored. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VenetoclaxAlso: ABT-199tablet, oral | Drug | Venetoclax + AMG 176 |
| AMG 176solution, intravenous | Drug | Venetoclax + AMG 176 |
Primary outcome
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.
10 secondary outcomes
Composite Complete Remission Rate (CRc) for Participants with AML
Time frame: Up to approximately 2 years from last subject first dose
Objective Response Rate (ORR) for Participants with AML
Time frame: Up to approximately 2 years from last subject first dose
ORR for Participants with NHL
Time frame: Up to approximately 2 years from last subject first dose
Maximum Plasma Concentration (Cmax) of Venetoclax
Time frame: Up to approximately 28 days after first dose of study drug
Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax
Time frame: Up to approximately 28 days after first dose of study drug
AUC of Venetoclax
Time frame: Up to approximately 28 days after first dose of study drug
Maximum Plasma Concentration (Cmax) of AMG 176
Time frame: Up to approximately 16 days after first dose of study drug
Half-life (t1/2) of AMG 176
Time frame: Approximately 16 days after first dose of study drug
AUC of AMG 176
Time frame: Approximately 16 days after first dose of study drug
Clearance (CL) of AMG 176
Time frame: Approximately 16 days after first dose of study drug
Results and safety
The study was stopped early (reason given: Safety). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2021.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
ABBVIE INC. study director
AbbVie
17 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Venetoclax and AMG 176 in people with Acute Myeloid Leukemia and Non-Hodgkin's Lymphoma, run by AbbVie at 17 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Germany, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Safety). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2021.