Acute Myeloid Leukemia (AML)Phase 1NCT03441555
A Study of Venetoclax and Alvocidib in Patients With Relapsed/Refractory Acute Myeloid Leukemia
A Phase 1 study testing Venetoclax and Alvocidib in people with Acute Myeloid Leukemia (AML), run by AbbVie at 14 sites in 3 countries.
Trial summary
An open-label, dose-escalation study to assess the safety and pharmacokinetics (PK), to determine the dose limiting toxicity (DLT) and the recommended Phase 2 dose (RPTD), and to assess the preliminary efficacy of alvocidib with venetoclax when co-administered in participants with relapsed or refractory (R/R) acute… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia (AML)
- What is being tested?
- Venetoclax and Alvocidib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 14 sitesin 3 countries
- Study dates
- 30 May 2018to 25 Jan 2021
- 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
- Must have adequate coagulation, hematology, kidney, and liver function, per protocol.
- Diagnosis of relapsed or refractory (R/R) acute myeloid leukemia (AML)
- Meet the following disease activity criteria:
- an established, confirmed diagnosis of AML by World Health Organization criteria excluding acute promyelocytic leukemia (APL)-M3; and
- an Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
- If male participant is sexually active, he must agree from day 1 through 6 months after the last dose of alvocidib or 90 days after the last dose of venetoclax, whichever is longer, to practice the protocol-specified protection.
Who cannot join
- History 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 within 6 months of study drug administration and no requirement for graft versus host therapy.
- History of previous enrollment in Studies NCT02993523 or NCT03069352.
- History of exposure to alvocidib or any other cyclin-dependent kinase 9 (CDK9) inhibitor.
- History of Tumor Lysis Syndrome (TLS) due to previous exposure to venetoclax.
Trial locations and contacts
14 sites in 3 countries.
14 sites in 3 countries
United States9 sites
Duke University Medical Center /ID# 170842
Durham, North Carolina, 27710-3000
Indiana Blood & Marrow Transpl /ID# 170793
Indianapolis, Indiana, 46237
USC Norris Cancer Center /ID# 170844
Los Angeles, California, 90033
Sylvester Comprehensive Cancer /ID# 170761
Miami, Florida, 33136-1002
NYU Langone Medical Center /ID# 201559
New York, New York, 10016-6402
Weill Cornell Medical College /ID# 170800
New York, New York, 10021
UC Irvine /ID# 201093
Orange, California, 92868
University of Pittsburgh Medic /ID# 170790
Pittsburgh, Pennsylvania, 15261
University of California, Davis Comprehensive Cancer Center /ID# 170799
Sacramento, California, 95817
United Kingdom3 sites
University Hospital of Wales /ID# 202302
Cardiff, CF14 4EN
Ninewells Hospital /ID# 202304
Dundee, DD1 9SY
St. James University Hospital /ID# 202303
Leeds, LS9 7TF
Germany2 sites
Universitaetsklinikum Dresden /ID# 168636
Dresden, 01307
Univ Klinik Eppendorf Hamburg /ID# 168633
Hamburg, 20246
About this study
Official title: Phase 1b Study of Venetoclax and Alvocidib in Patients With Relapsed/Refractory Acute Myeloid Leukemia
An open-label, dose-escalation study to assess the safety and pharmacokinetics (PK), to determine the dose limiting toxicity (DLT) and the recommended Phase 2 dose (RPTD), and to assess the preliminary efficacy of alvocidib with venetoclax when co-administered in participants with relapsed or refractory (R/R) acute myeloid leukemia (AML).
- Conditions
- Acute Myeloid Leukemia (AML)
- Being tested
- Venetoclax, Alvocidib
- Keywords
- Cancer, Acute Myeloid Leukemia (AML), relapsed Acute Myeloid Leukemia, refractory Acute Myeloid Leukemia
- Medical subject headings
- Leukemia, Myeloid, Acute, 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
AlvocidibDrug
Also called Flavopiridol
Intravenous
| Study group | Role | What they receive |
|---|---|---|
| Venetoclax + Alvocidib | Experimental | Venetoclax administered orally once daily (QD) and Alvocidib administered as an intravenous infusion on Days 1, 2, and 3 for all 28-day treatment cycles. Different combinations of dose levels for venetoclax and alvocidib may be explored. Receives: Drug: Venetoclax; Drug: Alvocidib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tmax of venetoclax
Time to maximum plasma concentration (Tmax) of venetoclax
Measured: Approximately 32 days after first dose of study drug
Clearance of Alvocidib
Clearance (CL) of alvocidib
Measured: Approximately 32 days after first dose of study drug
AUC0-∞ of Alvocidib
Area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) post-dose of alvocidib
Measured: Approximately 32 days after first dose of study drug
Cmax of Venetoclax
Maximum plasma concentration (Cmax) of venetoclax
Measured: Approximately 32 days after first dose of study drug
Half-life (t1/2) of Alvocidib
Half-life (t1/2) of alvocidib
Measured: Approximately 32 days after first dose of study drug
AUC0-24 Post-dose of Venetoclax
Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax.
Measured: Approximately 32 days after first dose of study drug
Cmax of Alvocidib
Maximum plasma concentration (Cmax) of alvocidib.
Measured: Approximately 32 days after first dose of study drug
AUCt Post-dose of Alvocidib
Area under the plasma concentration-time curve from time zero to time t (AUCt) post-dose alvocidib.
Measured: Approximately 32 days after first dose of study drug
Dose Escalation Phase: Recommended Phase 2 dose (RPTD) for Venetoclax and Alvocidib
RPTD will be determined using available safety and pharmacokinetics data upon completion of the dose escalation phase.
Measured: Minimum first cycle of dosing (up to 28 days)
Secondary outcomes (3)
Complete Response (CR) Rate
CR is defined as the proportion of participants with documented complete response (CR) based on International Working Group (IWG) criteria.
Measured: Up to approximately 8 months
Combined CR Rate
Combined CR rate is defined as CR + CRi (CR with incomplete blood count recovery) based on IWG criteria.
Measured: Up to approximately 8 months
Objective Response Rate (ORR)
ORR is defined as the proportion of participants with documented partial response (PR) or better based on IWG criteria.
Measured: Up to approximately 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2018
- Study start30 May 2018
- Primary completion25 Jan 2021
- Study completion25 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid Leukemia (AML)Studies 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
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Sumitomo Pharma America, Inc.
- Responsible party
- Sponsor
- Investigators
- AbbVie Inc., Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03441555
- Sponsor's protocol ID
- M16-186
- Other IDs
- 2017-002531-42, 2017
- Status last verified
- Jan 2022
- First submitted
- 16 Feb 2018
- Last updated
- 1 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- 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 1 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1b Study of Venetoclax and Alvocidib in Patients With Relapsed/Refractory Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT03441555
- Acronym / sponsor ID
- M16-186
- Conditions
- Acute Myeloid Leukemia (AML)
- Keywords
- Cancer, Acute Myeloid Leukemia (AML), relapsed Acute Myeloid Leukemia, refractory Acute Myeloid Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- AbbVieIndustry (pharma, biotech, devices)
- Collaborators
- Sumitomo Pharma America, Inc.
- Study start
- 30 May 2018 (actual)
- Primary completion
- 25 Jan 2021 (actual)
- Study completion
- 25 Jan 2021 (actual)
- First posted
- 22 Feb 2018 (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.
An open-label, dose-escalation study to assess the safety and pharmacokinetics (PK), to determine the dose limiting toxicity (DLT) and the recommended Phase 2 dose (RPTD), and to assess the preliminary efficacy of alvocidib with venetoclax when co-administered in participants with relapsed or refractory (R/R) acute myeloid leukemia (AML).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Venetoclax + Alvocidib | Experimental | Drug: Venetoclax, Drug: AlvocidibVenetoclax administered orally once daily (QD) and Alvocidib administered as an intravenous infusion on Days 1, 2, and 3 for all 28-day treatment cycles. Different combinations of dose levels for venetoclax and alvocidib may be explored. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Must have adequate coagulation, hematology, kidney, and liver function, per protocol.
- Diagnosis of relapsed or refractory (R/R) acute myeloid leukemia (AML)
- Meet the following disease activity criteria:
- an established, confirmed diagnosis of AML by World Health Organization criteria excluding acute promyelocytic leukemia (APL)-M3; and
- an Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
Key exclusion criteria (5 listed)
- History 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 within 6 months of study drug administration and no requirement for graft versus host therapy.
- History of previous enrollment in Studies NCT02993523 or NCT03069352.
- History of exposure to alvocidib or any other cyclin-dependent kinase 9 (CDK9) inhibitor.
- History of Tumor Lysis Syndrome (TLS) due to previous exposure to venetoclax.
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 + Alvocidib |
| AlvocidibAlso: FlavopiridolIntravenous | Drug | Venetoclax + Alvocidib |
Primary outcome
Tmax of venetoclax
Time frame: Approximately 32 days after first dose of study drug
Time to maximum plasma concentration (Tmax) of venetoclax
Clearance of Alvocidib
Time frame: Approximately 32 days after first dose of study drug
Clearance (CL) of alvocidib
AUC0-∞ of Alvocidib
Time frame: Approximately 32 days after first dose of study drug
Area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) post-dose of alvocidib
Cmax of Venetoclax
Time frame: Approximately 32 days after first dose of study drug
Maximum plasma concentration (Cmax) of venetoclax
Half-life (t1/2) of Alvocidib
Time frame: Approximately 32 days after first dose of study drug
Half-life (t1/2) of alvocidib
AUC0-24 Post-dose of Venetoclax
Time frame: Approximately 32 days after first dose of study drug
Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax.
Cmax of Alvocidib
Time frame: Approximately 32 days after first dose of study drug
Maximum plasma concentration (Cmax) of alvocidib.
AUCt Post-dose of Alvocidib
Time frame: Approximately 32 days after first dose of study drug
Area under the plasma concentration-time curve from time zero to time t (AUCt) post-dose alvocidib.
Dose Escalation Phase: Recommended Phase 2 dose (RPTD) for Venetoclax and Alvocidib
Time frame: Minimum first cycle of dosing (up to 28 days)
RPTD will be determined using available safety and pharmacokinetics data upon completion of the dose escalation phase.
3 secondary outcomes
Complete Response (CR) Rate
Time frame: Up to approximately 8 months
Combined CR Rate
Time frame: Up to approximately 8 months
Objective Response Rate (ORR)
Time frame: Up to approximately 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2022.
- Individual participant dataSharing planned: No
Related trials for Acute Myeloid Leukemia (AML)
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
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
14 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 Alvocidib in people with Acute Myeloid Leukemia (AML), run by AbbVie at 14 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 6 inclusion and 5 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: finished, as of the sponsor's last update on 1 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, United Kingdom, Germany. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Tmax of venetoclax (time frame: Approximately 32 days after first dose of study drug). The study lists 9 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 1 Feb 2022.