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Nucleoside Analog

ASTX727 + Venetoclax + Gilteritinib for Acute Myeloid Leukemia

Phase 1 & 2

Recruiting

Led By Farhad Ravandi-Kashani

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Ability to swallow

Adults >= 18 years with relapsed/refractory FLT3-mutated AML or myelodysplastic syndrome (MDS) that is intermediate-2 or high-risk by the International Prognostic Scoring System (Phase I cohort)

Must not have

Active grade III-V cardiac failure as defined by the New York Heart Association Criteria

Prior treatment with gilteritinib

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the combination of gilteritinib with ASTX727 and venetoclax to treat patients with FLT3-mutated acute myeloid leukemia or high-risk myelodysplastic syndrome.

Who is the study for?

Adults aged 18+ with FLT3-mutated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS), either newly diagnosed, relapsed, or refractory. Participants must have adequate organ function and performance status <=3 on the ECOG scale. Exclusions include prior gilteritinib treatment, more than three lines of therapy for Phase II cohort B, serious infections, heart failure, CNS leukemia, HIV positivity, hepatitis B/C infection.

What is being tested?

The trial is testing a combination of ASTX727 (decitabine and cedazuridine), venetoclax, and gilteritinib to determine the best dose and effect on AML/MDS with FLT3 mutation. The study aims to see if these drugs can control cancer growth by killing cells or stopping them from dividing/spreading.

What are the potential side effects?

Potential side effects may include reactions related to the immune system's response to the drugs causing inflammation in organs; gastrointestinal issues like nausea; blood-related problems such as anemia; liver enzyme alterations; fatigue; risk of infections due to weakened immunity.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can swallow without any issues.

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I am an adult with AML or MDS, my condition is high-risk, and I have a FLT3 mutation.

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My leukemia has FLT3 mutations.

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I am an adult with AML or MDS, have a FLT3 mutation, and have had one prior therapy.

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I can take care of myself but can't do heavy physical work.

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I am an adult with AML or MDS, have a FLT3 mutation, and my condition is considered high-risk.

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My AML diagnosis is recent and has a FLT3 mutation.

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I am 75 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have severe heart failure.

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I have been treated with gilteritinib before.

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I haven't taken medications like carbamazepine, phenytoin, rifampin, or St. John's wart in the last 3 days.

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I have leukemia that has spread to my brain.

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I have an ongoing serious infection not responding to antibiotics.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall response (OR) rate (Phase II)

Secondary study objectives

Complete response rate

Overall survival

Proportion of patients proceeding to hematopoietic stem cell transplantation

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (decitabine, cedazuridine, venetoclax, gilteritib)Experimental Treatment3 Interventions

INDUCTION (CYCLE 1): Patients receive decitabine and cedazuridine PO QD on days 1-5, venetoclax PO QD on days 1-28, and gilteritinib PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity CONSOLIDATION (CYCLES 2-24): Patients receive decitabine and cedazuridine PO QD on days 1-5, gilteritinib PO QD on days 1-28, and venetoclax PO QD on days 1-21. Treatment repeats every 28 days for up to 23 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE (CYCLES 24+): Patients receive gilteritinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Gilteritinib

2014

Completed Phase 2

~660

Venetoclax

2019

Completed Phase 3

~2240