Acute Myeloid LeukemiaPhase 1NCT05010772
Decitabine Alone or in Combination With Venetoclax, Gilteritinib, Enasidenib, or Ivosidenib as Maintenance Therapy for the Treatment of Acute Myeloid Leukemia in Remission
A Phase 1 study testing Decitabine and Cedazuridine, Enasidenib and Gilteritinib in people with Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase Ib trial is to find out the side effects and possible benefits of decitabine alone or given together with venetoclax, gilteritinib, enasidenib, or ivosidenib in treating patients with acute myeloid leukemia that is under control (remission). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Decitabine and Cedazuridine, Enasidenib and Gilteritinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 125 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Oct 2021to 31 Dec 2026
- Phase
- Phase 1
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
- Patients aged >= 18 years AML who have achieved their FIRST complete response (CR) or complete response with incomplete bone marrow recovery (CRi) and are not immediately candidates for allogeneic stem cell transplant
- Patients who have received intensive therapy (defined as receiving standard or higher dose cytarabine-based therapy) to achieve remission (CR/CRi) should have received remission induction therapy and at least 1 consolidation cycle. These patients are eligible as long as they are not greater than 2 months from their last consolidation therapy and will be designated as COHORT 1 (intensive induction cohort)
- Patients who have received lower intensity therapy (defined as receiving low-dose cytarabine [LDAC] or hypomethylating agent [HMA]-based therapy) to achieve remission should have received at least 2 cycles of lower intensity therapy between the time they have achieved CR/CRi and enrollment on this protocol. They will be designated as COHORT 2 (lower intensity induction cohort)
- For either subgroup (lower or higher intensity), patients who have measurable residual disease may be enrolled on their respective cohort at any time without maximum 'time from consolidation' requirement
- Eastern Cooperative Oncology Group (ECOG) performance status of < or = 3
- Serum total bilirubin < or = to 1.5 x the upper limit of normal (ULN)
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- Serum creatinine < or = to 2.5 x ULN
- Absolute neutrophil count (ANC) > 0.5 x k/uL
- Platelet count > or = 50 x k/uL
- For females of childbearing age, they may participate if they:
- Have a negative serum or urine pregnancy test within 10 to 14 days of enrolling
- Agree to either abstinence or 2 effective contraceptive methods (such as barrier methods or hormonal contraception) throughout the treatment period and up to 30 days after discontinuing treatment
- For male patients with a female partner of childbearing age, they may participate if they agree to either abstinence or 2 effective contraceptive methods throughout the treatment period and up to 30 days after discontinuing treatment
- Ability to understand and sign informed consent
Who cannot join
- Diagnosis of acute promyelocytic leukemia (APL), AML - M3 by French-American-British (FAB) classification based on morphology, immunophenotype, molecular, or cytogenetics studies
- Diagnosis of AML associated t(15;17) or APL variant. Patients with t(9;22) are also ineligible unless they are unable or unwilling to receive therapy with a tyrosine kinase inhibitor
- Uncontrolled intercurrent illness including, but not limited to active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Patients with active CNS (central nervous system) disease
- Patients with documented hypersensitivity to any components of the study program
- Females who are pregnant or lactating or intending to become pregnant during the study
- Patients with history of extramedullary AML, except for CNS involvement that is currently controlled, will not be eligible for enrollment
- Patient should be removed from current trial if they wish to participate and get treatment on another trial
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
M D Anderson Cancer Center
Houston, Texas, 77030
Tapan M. Kadia, 713-792-7305, tkadia@mdanderson.org
Tapan M. Kadia
About this study
Official title: Oral Decitabine-Based Maintenance Therapy in Patients With AML in Remission
This phase Ib trial is to find out the side effects and possible benefits of decitabine alone or given together with venetoclax, gilteritinib, enasidenib, or ivosidenib in treating patients with acute myeloid leukemia that is under control (remission). Chemotherapy drugs, such as decitabine, 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. Venetoclax may stop the growth of cancer cells by blocking a protein called Bcl-2 needed for cell growth. Gilteritinib, enasidenib, and ivosidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving decitabine alone or together with venetoclax, gilteritinib, enasidenib, or ivosidenib may help to control the disease.
Read the detailed description
PRIMARY OBJECTIVE:
- To assess safety of patients with acute myeloid leukemia (AML) treated with decitabine and cedazuridine (oral decitabine)-based combinations as maintenance therapy after achieving remission.
SECONDARY OBJECTIVES:
- To assess relapse-frees survival (RFS) of patients with AML treated with oral decitabine-based combinations as maintenance therapy.
II. To assess overall survival (OS) of patients with AML treated with oral decitabine-based combinations as maintenance therapy.
III. To assess event-free survival (EFS) of patients with AML treated with oral decitabine-based combinations as maintenance therapy.
IV. To assess the duration of remission (CRd) of patients with AML treated oral decitabine-based combinations as maintenance therapy.
- To assess the effects of oral decitabine-based combinations on dynamics of minimal residual disease and their relationship to outcomes.
EXPLORATORY OBJECTIVE:
- To evaluate RFS in (1) intensive induction cohort and (2) lower intensity induction cohort.
OUTLINE: Patients are assigned to 1 of 5 arms.
ARM A: Patients receive decitabine and cedazuridine orally (PO) once daily (QD) on days 1-3. Treatments repeat every 28 days for up to 4 weeks in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive decitabine and cedazuridine PO QD on days 1-3 and venetoclax PO QD on days 1-5. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
ARM C: Patients receive decitabine and cedazuridine PO QD on days 1-3 and gilteritinib PO QD on days 1-28. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
ARM D: Patients receive decitabine and cedazuridine PO QD on days 1-3 and enasidenib PO QD on days 1-28. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
ARM E: Patients receive decitabine and cedazuridine PO QD on days 1-3 and ivosidenib PO QD on days 1-28. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6-12 months.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Decitabine and Cedazuridine, Enasidenib, Gilteritinib, Ivosidenib, 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.
Decitabine and CedazuridineDrug
Also called ASTX727, C-DEC, CDA Inhibitor E7727/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Combination Agent ASTX727
Given PO
EnasidenibDrug
Also called AG-221, CC-90007 Free Base
Given PO
GilteritinibDrug
Also called ASP-2215, ASP2215
Given PO
IvosidenibDrug
Also called AG-120, Tibsovo
Given PO
VenetoclaxDrug
Also called ABT-0199, ABT-199, ABT199, GDC-0199
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm A (decitabine and cedazuridine) | Experimental | Patients receive decitabine and cedazuridine PO QD on days 1-3. Treatments repeat every 28 days for up to 4 weeks in the absence of disease progression or unacceptable toxicity. Receives: Drug: Decitabine and Cedazuridine |
| Arm B (decitabine and cedazuridine, venetoclax) | Experimental | Patients receive decitabine and cedazuridine PO QD on days 1-3 and venetoclax PO QD on days 1-5. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Receives: Drug: Decitabine and Cedazuridine; Drug: Venetoclax |
| Arm C (decitabine and cedazuridine, gilteritinib) | Experimental | Patients receive decitabine and cedazuridine PO QD on days 1-3 and gilteritinib PO QD on days 1-28. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Receives: Drug: Decitabine and Cedazuridine; Drug: Gilteritinib |
| Arm D (decitabine and cedazuridine, enasidenib) | Experimental | Patients receive decitabine and cedazuridine PO QD on days 1-3 and enasidenib PO QD on days 1-28. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Receives: Drug: Decitabine and Cedazuridine; Drug: Enasidenib |
| Arm E (decitabine and cedazuridine, ivosidenib) | Experimental | Patients receive decitabine and cedazuridine PO QD on days 1-3 and ivosidenib PO QD on days 1-28. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Receives: Drug: Decitabine and Cedazuridine; Drug: Ivosidenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Safety analyses in general will be descriptive and will be presented in tabular format with the appropriate summary statistics. Adverse events will be tabulated using frequency and percentage by severity and by relations to the treatments for each arm.
Measured: Up to 5 years
Secondary outcomes (5)
Relapse-free survival (RFS)
The Kaplan-Meier method will be used to estimate RFS.
Measured: From complete remission or complete remission with incomplete count recovery until date of first objective documentation of relapse or death, assessed up to 5 years
Overall survival (OS)
The Kaplan-Meier method will be used to estimate OS.
Measured: From date of treatment start until date of death due to any cause, assessed up to 5 years
Event-free survival (EFS)
Event will be defined as: confirmed relapse, withdrawal from study due to adverse event, or death due to any cause. The Kaplan-Meier method will be used to estimate EFS.
Measured: From treatment start until date of first documented event., assessed up to 5 years
Duration of remission
The Kaplan-Meier method will be used to duration of remission.
Measured: Up to 5 years
Minimal residual disease
The log rank test and Cox proportional hazards model will be used to evaluate the association between the time to event outcomes and status of residual disease.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2021
- Study start25 Oct 2021
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (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.
- More trials run by M.D. Anderson Cancer CenterThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 125 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Tapan M Kadia, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05010772
- Sponsor's protocol ID
- 2021-0237
- Other IDs
- NCI-2021-08496, 2021-0237
- Status last verified
- Oct 2026
- First submitted
- 11 Aug 2021
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No