Acute Myeloid LeukemiaPhase 2NCT03466294
Azacitidine and Venetoclax as Induction Therapy With Venetoclax Maintenance in the Elderly With AML
A Phase 2 study testing Azacitidine and Venetoclax in people with Acute Myeloid Leukemia, run by University of Colorado, Denver at 1 site in United States.
Trial summary
This study is being done to determine if treatment with azacitidine and venetoclax is effective treatment for elderly patients with acute myeloid leukemia (AML) who have not received previous treatment. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Azacitidine and Venetoclax
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 15 May 2018to 4 Dec 2025
- Phase
- Phase 2
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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject must have confirmation of non-APL AML by WHO criteria and be ineligible or unwilling to undergo treatment with a standard cytarabine and anthracycline induction regimen due to co-morbidities or other factors
- Subject must have received no prior treatment for AML; hydroxyurea is not considered a treatment and is allowed
- Subject must be ≥ 60 years of age
- Subject must have a projected life expectancy of at least 12 weeks
- Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status of ≤2
- Subject must have adequate renal function as demonstrated by a calculated creatinine clearance ≥ 30 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula
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- Subject must have adequate liver function as demonstrated by:
- aspartate aminotransferase (AST) ≤ 3.0 × ULN*
- alanine aminotransferase (ALT) ≤ 3.0 × ULN*
- bilirubin ≤ 3.0 × ULN, unless due to Gilbert's syndrome*
- Unless considered due to leukemic organ involvement
- Non-sterile male subjects must use contraceptive methods with partner(s) prior to beginning study drug administration and continuing up to 90 days after the last dose of study drug. Male subjects must agree to refrain from sperm donation from initial study drug administration until 90 days after the last dose of study drug.
- Female subjects must be either:
- Postmenopausal; defined as Age > 55 years with no menses for 12 or more months without an alternative medical cause; OR
- Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
- Subject must voluntarily sign and date an informed consent, approved by an Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.
Who cannot join
- Subject has received treatment with a hypomethylating agent and/or other chemotherapeutic agent either conventional or experimental for myelodysplastic syndrome (MDS) or AML
- Subject has acute promyelocytic leukemia
- Subject has known active CNS involvement from AML
- Subject is known to be positive for HIV. HIV testing is not required
- Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load. Hepatitis B or C testing is not required and subjects with serologic evidence of prior vaccination to HBV (i.e., HBs Ag, anti-HBs+ and anti-HBc-) may participate
- Subject has received anticancer therapies including chemotherapy, radiotherapy or other investigational therapy, including targeted small molecule agents within 5 half-lives prior to first dose of study drug
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- Subject has received biologic agents (e.g. monoclonal antibodies) for anti-neoplastic intent within 30 days prior to first dose of study drug
- Subject has received the following within 7 days prior to the first dose of the study drug:
- Steroid therapy for anti-neoplastic intent;
- Strong and Moderate CYP3A inhibitors (see Appendix A for examples)
- Strong and Moderate CYP3A inducers (see Appendix A for examples)
- Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit within 3 days prior to the initiation of study treatment
- Subject has any history of clinically significant condition(s) that in the opinion of the investigator would adversely affect his/her participating in this study including, but not limited to:
- New York Heart Association heart failure > class 2
- Renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or bleeding disorder independent of leukemia
- Subject has a malabsorption syndrome or other condition that precludes enteral route of administration
- Subject exhibits evidence of uncontrolled systemic infection requiring therapy (viral, bacterial or fungal)
- Subject has a history of other malignancies prior to study entry, with the exception of:
- Adequately treated in situ carcinoma of the breast or cervix uteri
- Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin
- Prostate cancer with no plans for therapy of any kind
- Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent
- Subject has a white blood cell count > 25 × 109/L. Note: hydroxyurea is permitted to meet this criteria
- Any subject who is a candidate for intensive induction therapy and agrees to receive this therapy
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Denver
Aurora, Colorado, 80045
About this study
Official title: Azacitidine and Venetoclax (ABT-199) as Induction Therapy With Venetoclax Maintenance in Previously Untreated Elderly Patients With Acute Myeloid Leukemia (AML)
This study is being done to determine if treatment with azacitidine and venetoclax is effective treatment for elderly patients with acute myeloid leukemia (AML) who have not received previous treatment. Azacitidine and venetoclax will be given as induction treatment followed by venetoclax maintenance treatment for patients who respond to the induction treatment.
Read the detailed description
This is a phase 2 study for elderly patients who have not received previous treatment for acute myeloid leukemia (AML). Up to 42 patients will be enrolled. All patients will be treated with azacitidine and venetoclax until a minimal residual disease (MRD) negative response is achieved. Once patients achieve a MRD negative composite response, azacitidine will be discontinued and venetoclax dose will be decreased to "maintenance" dose.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Azacitidine and Venetoclax
- Keywords
- Azacitidine, Venetoclax, AML
- 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.
Azacitidine and VenetoclaxDrug
Azacitidine will be given at dose of 75mg/m2 in Cycle 1 days 1-7; repeat in cycle 2 and 3 if no response. Starting on day 2 of cycle 1, venetoclax will be administered orally with doses increased to a target dose of 600 mg (administer 100 mg on day 2, 200 mg on day 3, 400 mg on day 4 and 600 mg on day 5), then 600 mg daily.
| Study group | Role | What they receive |
|---|---|---|
| Azacitidine and Venetoclax | Experimental | On day 1 of cycle 1, Azacitidine 75 mg/m2 will be given by injection or infusion, and will continue for 7 days. Azacitidine doses will be given in subsequent cycles for patients who do not achieve response. Venetoclax will be administered orally once daily on days 2 through 28 in cycle 1. Beginning with cycle 2, and each subsequent cycle, venetoclax will be administered Days 1 through 28. Receives: Drug: Azacitidine and Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Duration of Remission Response to Azacitidine and Venetoclax Treatment + Maintenance Therapy
To determine the remission duration experienced by elderly previously untreated AML patients with azacitidine plus venetoclax followed by venetoclax alone as a maintenance therapy for patients who achieve a minimal residual disease (MRD) negative remission
Measured: From the first day a response is documented to the first day of disease progression
Secondary outcomes (3)
Response Rate, With Responses Defined as Complete Remission (CR), Complete Remission With Incomplete Blood Count Recovery (CRi) and Morphologic Leukemia Free State (MLFS).
To determine the rate of MRD negative composite responses (includes complete remission [CR], complete remission with incomplete count recovery [CRi], and morphologic leukemia free state [MLFS]) with azacitidine plus venetoclax.
Measured: From Day 28, the first day a response is documented to end of cycle bone marrow biopsies, through 5 years
MRD-Negativity Incidence
MRD assessments by flow cytometry were employed for patients who achieved CR/CRI/MLFS. MRD-negative by this modality was defined as no evidence of aberrant myeloid antigen expression or abnormal myeloblasts at a level of detection <0.1% in an adequate sample.
Measured: From Day 28, the first day a response is documented to end of cycle bone marrow biopsies, through 5 years
To Determine the Median Time to Achieve a MRD Negative Composite Response
The median time to achieve MRD negative composite response
Measured: From first dose of treatment to first day response is documented by bone marrow biopsy, on average 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2018
- Study start15 May 2018
- Primary completion29 Jan 2025
- Study completion4 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dan Pollyea, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03466294
- Sponsor's protocol ID
- 17-7821.cc
- Status last verified
- Apr 2026
- First submitted
- 2 Mar 2018
- Last updated
- 9 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Shallis RM, Podoltsev NA. Maintenance therapy for acute myeloid leukemia: sustaining the pursuit for sustained remission. Curr Opin Hematol. 2021 Mar 1;28(2):110-121. doi: 10.1097/MOH.0000000000000637.
PubMed 33394722