Acute Myeloid LeukemiaPhase 2NCT04905810
Azacitidine or Decitabine With Venetoclax for Acute Myeloid Leukemia With Prior Hypomethylating Agent Failure
A Phase 2 study testing Azacitidine, Decitabine and Venetoclax in people with Acute Myeloid Leukemia and Recurrent Acute Myeloid Leukemia, run by Brian Jonas at 4 sites in United States.
Trial summary
This phase II trial evaluates the effect of azacitidine or decitabine and venetoclax in treating patients with acute myeloid leukemia that has not been treated before (treatment naive) or has come back (relapsed). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Recurrent Acute Myeloid Leukemia
- What is being tested?
- Azacitidine, Decitabine and Venetoclax
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 4 sitesUnited States
- Study dates
- 9 Feb 2022to 1 Dec 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Ability to understand and the willingness to sign a written informed consent
- Diagnosis of AML by World Health Organization (WHO) 2016 criteria (Arber 2016)
- Age >= 18 years
- Treatment naïve and eligible for venetoclax plus HMA: * Age >= 75 OR * Age >= 18-74 with at least one of the following co-morbidities: Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3 Cardiac history of chronic heart failure (CHF) requiring treatment or left ventricular ejection fraction (LVEF) =< 50% or chronic unstable angina Carbon monoxide diffusing capability (DLCO) =< 65% or forced expiratory volume in 1 second (FEV1) =< 65% Creatinine clearance >= 30 mL/min to =< 45 mL/min Moderate hepatic impairment with total bilirubin > 1.5 to =< 3 x upper limit of normal (ULN) Any other situation that the investigator judges to be incompatible with intensive chemotherapy must be reviewed with the study chair before study enrollment
- Patient experienced HMA failure for an antecedent hematologic disorder (e.g. myelodysplastic syndrome) prior to study entry (Santini 2019), defined as: * Disease progression or stable disease as best response to >= 4 cycles of HMA or >= 2 cycles of HMA combination therapy (primary resistance) OR * Relapse or progression after prior response to HMA (secondary resistance)
- Prior decitabine and/or azacitidine, including oral formulations, for antecedent hematologic disorder is required. The patient should be treatment naïve for the AML diagnosis
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- Prior allogeneic hematopoietic transplant for antecedent hematologic disorder is allowed if done at least 3 months prior to enrollment and there is no evidence of active graft versus host disease (GVHD) or requirement for systemic immune suppression
- ECOG performance status of: * 0 to 2 for subjects >= 75 years of age OR * 0 to 3 for subjects >= 18-74 years of age
- Whole blood cell (WBC) >= 25,000/mm^3 at the start of study therapy (leukapheresis and hydroxyurea areallowed to meet this criteria)
- Total bilirubin =, 1.5 x institution's ULN unless related to AML or Gilbert's syndrome (subjects who are >= 18-74 may have a total bilirubin of =< 3 x institution's ULN)
- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SPGT) =< 3 x institutional ULN unless related to AML
- Creatinine clearance >= 30 mL/min (calculated by the Cockcroft Gault formula or measured by 24-hours urine collection)
- Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
- Women of child-bearing potential has negative pregnancy test prior to initiating study drug dosing
- Able to swallow and retain oral medication
Who cannot join
- Current or anticipated use of other investigational agents within 14 days or 5 half-lives (whichever is shorter) prior to the first dose and throughout venetoclax administration
- Diagnosis of acute promyelocytic leukemia
- Active central nervous system involvement by AML
- Anticancer therapies, including investigational therapy, chemotherapy, targeted small molecule agents, or radiotherapy within 14 days or 5 half-lives (whichever is shorter) prior to the first dose and throughout venetoclax administration. Biologic agents (e.g. monoclonal antibodies) given for anti-neoplastic intent within 30 days prior to the first dose and throughout venetoclax administration
- Prior therapy with venetoclax
- Known diagnosis of human immunodeficiency virus (HIV) infection or known active hepatitis A, B or C infection with the exception of those with an undetectable viral load and CD4+ T-cell (CD4+) counts >= 350 cells/μL within 3 months of starting study treatment. Should have no titers within 28d of day 1. Patients with hepatitis C virus (HCV) infection should have completed curative antiviral treatment
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- Known strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment
- Subject has consumed grapefruit, grapefruit products, Seville oranges or starfruit within 3 days prior to the initiation of study treatment
- Severe or uncontrolled medical disorder that would, in the investigator's opinion, impair ability to receive study treatment (i.e., uncontrolled diabetes, chronic renal disease, chronic pulmonary disease or active, uncontrolled infection, psychiatric illness/social situations that would limit compliance with study requirements)
- History of other malignancies, except for malignancy treated with curative intent with no known active disease present for >= 1 year; treated non-melanoma skin cancer; and localized, cured prostate and cervical cancer
- Evidence of uncontrolled active systemic infection requiring therapy (viral, bacterial, or fungal). Fever of unknown origin is not an exclusion criterion, as this may be disease related
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study
- Subject has a malabsorption syndrome of other condition that precludes enteral route of administration
- Subjects with a cardiovascular disability status of New York Heart Association class greater than 2
- Pregnant or nursing. There is a potential for congenital abnormalities and for this regimen to harm nursing infants
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 4 recruiting
- Recruiting
UCSF-Fresno
Clovis, California, 93611
Mohammed Bukari, MD, 559-387-1900 ext. 41936, mohammed.bukari@ucsf.edu
Mohammed Bukari, MD
- Not yet recruiting
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
Caspian Oliai, 310-206-6909, COliai@mednet.ucla.edu
Caspian Oliai
- Not yet recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Matthew J. Wieduwilt, 405-217-8001, Matthew-Wieduwilt@ouhsc.edu
Matthew J. Wieduwilt
- Recruiting
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Brian A. Jonas, 916-734-3771, bajonas@ucdavis.edu
Brian A. Jonas
About this study
Official title: Phase II Study of Venetoclax With Alternative Hypomethylating Agent for Patients With Acute Myeloid Leukemia With Prior Hypomethylating Agent Failure: A University of California Hematologic Malignancies Consortium Protocol
This phase II trial evaluates the effect of azacitidine or decitabine and venetoclax in treating patients with acute myeloid leukemia that has not been treated before (treatment naive) or has come back (relapsed). Chemotherapy drugs, such as azacitidine, decitabine, and venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Read the detailed description
PRIMARY OBJECTIVE: I. To evaluate the efficacy of venetoclax plus alternative hypomethylating agent (HMA), as defined by the primary endpoint of overall response rate, for patients with treatment naive acute myeloid leukemia (AML) eligible for venetoclax plus HMA with prior HMA failure.
SECONDARY OBJECTIVES:
- To further examine the efficacy of venetoclax plus alternative HMA for patients with treatment naive AML eligible for venetoclax plus HMA with prior HMA failure using additional efficacy endpoints.
II. To further evaluate the safety of venetoclax plus alternative HMA for patients with treatment naive AML eligible for venetoclax plus HMA with prior HMA failure.
- Being tested
- Azacitidine, Decitabine, Venetoclax
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called 5 AZC, 5-AC, 5-Azacytidine, 5-AZC
Given IV
DecitabineDrug
Also called 5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine
Given IV
VenetoclaxDrug
Also called ABT-0199, ABT-199, ABT199, GDC-0199
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (azacitidine, decitabine, venetoclax) | Experimental | Patients receive azacitidine IV over 10-40 minutes or SC on days 1-7 (for patients with prior decitabine use), or decitabine IV on days 1-5 (for patients with prior azacitidine), and venetoclax PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Azacitidine; Drug: Decitabine; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate
Will be defined as the rate of complete remission (CR) plus CR with incomplete count recovery (CRi).
Measured: Up to 1 year
Secondary outcomes (8)
Measurable/minimal residual disease (MRD) status
Will be measured by multiparameter flow cytometry and/or molecular methods (e.g. real-time quantitative reverse transcription [qRT-PCR]). Will be assessed in patients achieving a CR, CRi or CR with partial hematologic recovery (CRh). Rates of MRD negative CR+CRi and CR+CRh will be calculated.
Measured: Up to 1 year
Rate of CR/CRh
Will be defined as the rate of complete remission (CR) plus CR with partial hematologic recovery (CRh).
Measured: Up to 1 year
Rate of transfusion-independence
Transfusion independence (TI) is defined as any period of >/= 56 days during treatment with no RBC or platelet transfusion.
Measured: Up to 1 year
Duration of CR/CRi (DoR)
Time from the date of CR/CRi until the date of relapse or death
Measured: From the date of CR/CRi until the date of relapse or death, assessed up to 1 year
Relapse-free survival
Time from the date of entry into study to the date of relapse or death from any cause
Measured: From the date of CR/CRi until the date of relapse or death from any cause, assessed up to 1 year
Event-free survival
Time from the date of entry into study to the date of treatment failure, relapse, or death from any cause
Measured: From the date of entry into study to the date of treatment failure, relapse, or death from any cause, assessed up to 1 year
Overall survival
Time from the date of entry into study to the date of death from any cause
Measured: From the date of entry into study to the date of death from any cause, assessed up to 1 year
Incidence of adverse events
Will be captured and characterized by type, frequency, severity (as defined and graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 toxicity criteria), timing, seriousness, and relationship to treatment.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2021
- Study start9 Feb 2022
- Primary completion1 May 2025 (estimated)
- Study completion1 Dec 2025 (estimated)
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.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brian Jonas
- Sponsor type
- University, hospital or other
- Collaborators
- AbbVie, National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Brian Jonas, University of California, Davis
- Investigators
- Brian A Jonas, Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04905810
- Sponsor's protocol ID
- UCDCC#293
- Other IDs
- NCI-2021-04009, UCDCC#293, P30CA093373
- Status last verified
- May 2024
- First submitted
- 24 May 2021
- Last updated
- 29 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Venetoclax With Alternative Hypomethylating Agent for Patients With Acute Myeloid Leukemia With Prior Hypomethylating Agent Failure: A University of California Hematologic Malignancies Consortium Protocol
- ClinicalTrials.gov ID
- NCT04905810
- Acronym / sponsor ID
- UCDCC#293
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Brian JonasUniversity, hospital or other
- Collaborators
- AbbVie, National Cancer Institute (NCI)
- Study start
- 9 Feb 2022 (actual)
- Primary completion
- 1 May 2025 (estimated)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 28 May 2021 (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 phase II trial evaluates the effect of azacitidine or decitabine and venetoclax in treating patients with acute myeloid leukemia that has not been treated before (treatment naive) or has come back (relapsed). Chemotherapy drugs, such as azacitidine, decitabine, and venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Detailed description
PRIMARY OBJECTIVE: I. To evaluate the efficacy of venetoclax plus alternative hypomethylating agent (HMA), as defined by the primary endpoint of overall response rate, for patients with treatment naive acute myeloid leukemia (AML) eligible for venetoclax plus HMA with prior HMA failure.
SECONDARY OBJECTIVES:
- To further examine the efficacy of venetoclax plus alternative HMA for patients with treatment naive AML eligible for venetoclax plus HMA with prior HMA failure using additional efficacy endpoints.
II. To further evaluate the safety of venetoclax plus alternative HMA for patients with treatment naive AML eligible for venetoclax plus HMA with prior HMA failure.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (azacitidine, decitabine, venetoclax) | Experimental | Drug: Azacitidine, Drug: Decitabine, Drug: VenetoclaxPatients receive azacitidine IV over 10-40 minutes or SC on days 1-7 (for patients with prior decitabine use), or decitabine IV on days 1-5 (for patients with prior azacitidine), and venetoclax PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Ability to understand and the willingness to sign a written informed consent
- Diagnosis of AML by World Health Organization (WHO) 2016 criteria (Arber 2016)
- Age >= 18 years
- Treatment naïve and eligible for venetoclax plus HMA: * Age >= 75 OR * Age >= 18-74 with at least one of the following co-morbidities: Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3 Cardiac history of chronic heart failure (CHF) requiring treatment or left ventricular ejection fraction (LVEF) =< 50% or chronic unstable angina Carbon monoxide diffusing capability (DLCO) =< 65% or forced expiratory volume in 1 second (FEV1) =< 65% Creatinine clearance >= 30 mL/min to =< 45 mL/min Moderate hepatic impairment with total bilirubin > 1.5 to =< 3 x upper limit of normal (ULN) Any other situation that the investigator judges to be incompatible with intensive chemotherapy must be reviewed with the study chair before study enrollment
- Patient experienced HMA failure for an antecedent hematologic disorder (e.g. myelodysplastic syndrome) prior to study entry (Santini 2019), defined as: * Disease progression or stable disease as best response to >= 4 cycles of HMA or >= 2 cycles of HMA combination therapy (primary resistance) OR * Relapse or progression after prior response to HMA (secondary resistance)
Key exclusion criteria (15 listed)
- Current or anticipated use of other investigational agents within 14 days or 5 half-lives (whichever is shorter) prior to the first dose and throughout venetoclax administration
- Diagnosis of acute promyelocytic leukemia
- Active central nervous system involvement by AML
- Anticancer therapies, including investigational therapy, chemotherapy, targeted small molecule agents, or radiotherapy within 14 days or 5 half-lives (whichever is shorter) prior to the first dose and throughout venetoclax administration. Biologic agents (e.g. monoclonal antibodies) given for anti-neoplastic intent within 30 days prior to the first dose and throughout venetoclax administration
- Prior therapy with 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 |
|---|---|---|
| AzacitidineAlso: 5 AZC, 5-AC, 5-Azacytidine, 5-AZCGiven IV | Drug | Treatment (azacitidine, decitabine, venetoclax) |
| DecitabineAlso: 5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, DeoxyazacytidineGiven IV | Drug | Treatment (azacitidine, decitabine, venetoclax) |
| VenetoclaxAlso: ABT-0199, ABT-199, ABT199, GDC-0199Given PO | Drug | Treatment (azacitidine, decitabine, venetoclax) |
Primary outcome
Overall response rate
Time frame: Up to 1 year
Will be defined as the rate of complete remission (CR) plus CR with incomplete count recovery (CRi).
8 secondary outcomes
Measurable/minimal residual disease (MRD) status
Time frame: Up to 1 year
Rate of CR/CRh
Time frame: Up to 1 year
Rate of transfusion-independence
Time frame: Up to 1 year
Duration of CR/CRi (DoR)
Time frame: From the date of CR/CRi until the date of relapse or death, assessed up to 1 year
Relapse-free survival
Time frame: From the date of CR/CRi until the date of relapse or death from any cause, assessed up to 1 year
Event-free survival
Time frame: From the date of entry into study to the date of treatment failure, relapse, or death from any cause, assessed up to 1 year
Overall survival
Time frame: From the date of entry into study to the date of death from any cause, assessed up to 1 year
Incidence of adverse events
Time frame: Up to 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2024.
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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.
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, United States
University of California Davis Comprehensive Cancer Center
Sacramento, United States
Brian A Jonas principal investigator
University of California, Davis
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Azacitidine, Decitabine and Venetoclax in people with Acute Myeloid Leukemia and Recurrent Acute Myeloid Leukemia, run by Brian Jonas at 4 sites in United States.
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 15 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 29 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (time frame: Up to 1 year). 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 29 May 2024.