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Nucleoside analogues

Venetoclax + Azacitidine for Acute Myeloid Leukemia

Phase 2

Recruiting

Led By Amir T Fathi, MD

Research Sponsored by Massachusetts General Hospital

Eligibility Criteria Checklist

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

Must have

Participants must have pathologically confirmed, newly diagnosed acute myeloid leukemia (AML). The AML may be either: De Novo: AML in patients with no clinical history of prior myelodysplastic syndrome (MDS), myeloproliferative disorder, or exposure to potentially leukemogenic therapies or agents; Secondary AML (sAML): refers to an acute leukemic process (1) evolving from known prior myelodysplasia, myeloproliferative disorder, or aplastic anemia with or without treatment or; (2) as a product of previous exposure to a proven leukemogenic chemotherapeutic agent

The effects of venetoclax on the developing human fetus are unknown. For this reason and because other chemotherapeutic agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Women should use contraceptives for at least 30 days following the last dose of venetoclax. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of therapy.

Must not have

Patients with FLT3-mutated AML (TKD or ITD)

Patients < 60 years old with NPM1-mutated AML

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial will compare the efficacy of the investigational combination versus standard of care in patients with induction-eligible acute myeloid leukemia.

Who is the study for?

Adults diagnosed with newly confirmed acute myeloid leukemia (AML), either de novo or secondary, who are eligible for intensive chemotherapy. Participants must be over 18, have an ECOG performance status ≤2, adequate liver function and heart health, and not have received prior AML treatment except hydroxyurea for cytoreduction. They must agree to use contraception due to unknown effects of venetoclax on fetuses.

What is being tested?

The trial is testing the effectiveness of a combination therapy using azacitidine and venetoclax against standard induction chemotherapy options like cytarabine with idarubicin or daunorubicin, or liposomal daunorubicin and cytarabine in patients with acute myeloid leukemia.

What are the potential side effects?

Potential side effects include nausea, vomiting, diarrhea, low blood counts leading to increased infection risk or bleeding problems. There may also be liver issues indicated by abnormal tests results and potential heart problems such as irregular heartbeat.

Eligibility Criteria

Inclusion Criteria

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

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I have been newly diagnosed with acute myeloid leukemia (AML) without previous cancer treatments.

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I agree to use effective birth control during and after the study.

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I have been newly diagnosed with acute myeloid leukemia (AML), without prior related diseases or treatments.

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My liver tests are within the normal range.

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My liver tests are within normal limits, except for conditions like Gilbert's syndrome.

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I can take care of myself but might not be able to do heavy physical work.

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I am 18 years old or older.

Exclusion Criteria

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

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My AML is FLT3-mutated.

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I am under 60 and have AML with an NPM1 mutation.

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I refuse blood products or am allergic to them.

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I have an active hepatitis B or C infection.

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I do not have severe heart failure or significant heart dysfunction.

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I am allergic or react badly to the trial drugs or standard chemotherapy.

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I do not have GI conditions or surgeries that affect drug absorption.

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I have been diagnosed with a specific type of leukemia that is considered to have a favorable outlook.

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I have a type of acute leukemia that doesn't fit into standard categories.

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I have been treated with drugs like azacitidine or decitabine before.

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I have had a bone marrow transplant for a blood cancer.

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I do not have any severe illnesses that my doctors are still trying to control.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from the time from randomization to time for up to 3 years, per protocol.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from the time from randomization to time for up to 3 years, per protocol.

This trial's timeline: 3 weeks for screening, Varies for treatment, and from the time from randomization to time for up to 3 years, per protocol. for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Event free survival

Secondary study objectives

100-Day post-transplant mortality

30-day mortality

60-day mortality

+16 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: Standard of Care (Conventional Induction)Experimental Treatment4 Interventions

Randomized participants will receive cytarabine and idarubicin \[or daunorubicin) per standard of care as follows: Induction: cytarabine on days 1-7 and idarubicin (or daunorubicin) on days 1-3 of induction. Second Induction (if needed): Cytarabine on days 1-5 and idarubicin (or daunorubicin) on days 1-2 of re-induction. Consolidation (if needed): If \< 60 years, cytarabine days 1,3,5 of consolidation cycles, and if ≥60 years, cytarabine days 1-5 of consolidation cycles Those with secondary or therapy-related AML can receive liposomal daunorubicin and cytarabine (Vyxeos) per standard of care as follows: Induction: Liposomal daunorubicin and cytarabine (Vyxeos) on Days 1,3, 5 of induction. Second Induction (if needed): Liposomal daunorubicin and cytarabine (Vyxeos) on days 1,3 of re-induction Consolidation (if needed): liposomal daunorubicin and cytarabine (Vyxeos) on days 1,3 of consolidation cycles

Group II: Investigational (Venetoclax and Azacitidine)Experimental Treatment2 Interventions

Participants will receive azacitidine on days 1-7 and venetoclax daily for up to (3) three 28-day study cycles and evaluated for response or benefit. If benefit/response is achieved, azacitidine on days 1-7 and venetoclax on days 1-28 (or less if deemed necessary per protocol) will be given in repeating 28-day cycles until benefit/response is no longer achieved or until patient proceeds to transplantation.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Daunorubicin

2013

Completed Phase 4

~5740

Cytarabine

2016

Completed Phase 3

~4020