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DNA Methyltransferase Inhibitor

Azacitidine + Venetoclax + Pevonedistat for Acute Myeloid Leukemia

Phase 1 & 2

Waitlist Available

Led By Nicholas Short

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

MDS/CMML POST-HMA FAILURE COHORT ONLY: Diagnosis of MDS or CMML with intermediate-1, intermediate-2, or high-risk disease by the IPSS who have no responded, progressed, or relapsed after treatment with at least 4 cycles of azacitidine and/or decitabine

NEWLY DIAGNOSED MDS/CMML COHORT ONLY: Diagnosis of MDS or CMML with intermediate-2 or high-risk disease by the International Prognostic Scoring System (IPSS)

Must not have

Known hypersensitivity to azacitidine, mannitol, pevonedistat, any of their components, or compounds of similar chemical composition

Patients whose only site of disease is extramedullary

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to cycle 24, day 28

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new combination of drugs to treat acute myeloid leukemia.

Who is the study for?

This trial is for adults with newly diagnosed acute myeloid leukemia who have not received certain previous treatments and are not suitable for intensive chemotherapy. They should be in a relatively good physical state (ECOG 0-2), able to practice effective contraception, and have adequate organ function. Those with severe infections, heart conditions, or other serious health issues unrelated to cancer are excluded.

What is being tested?

The study is testing the combination of three drugs: Azacitidine, Venetoclax, and Pevonedistat. It aims to find the best dose of Venetoclax alongside the other two drugs and evaluate how well this trio works together against acute myeloid leukemia by stopping cancer cells from growing.

What are the potential side effects?

Potential side effects may include nausea, vomiting, diarrhea, fatigue, risk of infection due to low blood cell counts, liver problems indicated by yellowing skin or eyes (jaundice), shortness of breath if lung problems occur. The severity can vary from mild discomforts to more serious complications.

Eligibility Criteria

Inclusion Criteria

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

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I have MDS or CMML and my treatment with azacitidine or decitabine did not work.

Select...

I have been newly diagnosed with MDS or CMML and it is considered intermediate-2 or high-risk.

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I am able to care for myself and perform daily activities.

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I have had chemotherapy or radiation for a different cancer.

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I have a history of Myelodysplastic Syndromes (MDS).

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I have a history of specific blood disorders and my cancer does not involve the BCR-ABL gene.

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I have MDS or CMML and my treatment with azacitidine or decitabine for at least 4 cycles did not work.

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I am a male using effective contraception or practicing abstinence.

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I am able to get out of my bed or chair and move around.

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I have a history of a specific blood disorder like PV, ET, or MF.

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My condition involves a genetic abnormality related to MDS, not including del9q.

Exclusion Criteria

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

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I am allergic to azacitidine, mannitol, pevonedistat, or similar drugs.

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My cancer is only present outside the bone marrow.

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I am HIV positive with a CD4 count over 350, undetectable viral load, on specific HIV meds, and no severe infections.

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I do not have a life-threatening illness with a life expectancy of less than 1 year.

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I have a severe lung condition like COPD, lung scarring, or fibrosis.

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I am willing and able to undergo strong chemotherapy for AML.

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I have been diagnosed with acute promyelocytic leukemia.

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I have not had major surgery in the last 14 days.

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I have severe liver problems or cirrhosis.

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I am currently pregnant, breastfeeding, or lactating.

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I have a known heart or lung condition.

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I do not have any severe or uncontrolled infections.

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I do not have a severe bleeding disorder unrelated to leukemia.

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I do not have another cancer that could affect this treatment's safety or results.

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My cancer has spread to my brain or spinal cord.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to cycle 24, day 28

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to cycle 24, day 28

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to cycle 24, day 28 for reporting.

Treatment Details

Study Objectives

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

Secondary study objectives

Incidence of adverse events

Minimal residual disease negativity rate

Side effects data

From 2022 Phase 3 trial • 389 Patients • NCT02005471

33%

Neutropenia

11%

SARS-CoV-2 test positive

11%

Sepsis

11%

Abdominal pain

11%

Pneumonia

11%

Rhinovirus infection

11%

COVID-19

11%

Gastroenteritis

11%

Pneumonia pseudomonal

11%

Electrocardiogram QT prolonged

11%

Anaemia

11%

Neutrophil count decreased

11%

Hypokalaemia

11%

Febrile neutropenia

11%

Supraventricular tachycardia

11%

Blood creatinine increased

11%

White blood cell count decreased

11%

Dermatitis

100%

80%

60%

40%

20%

Study treatment Arm

Bendamustine + Rituximab Crossover Substudy

Venetoclax + Rituximab Re-Treatment Substudy

Venetoclax + Rituximab Main Study

Bendamustine + Rituximab Main Study

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 (venetoclax, azacitidine, pevonedistat)Experimental Treatment3 Interventions

Patients receive venetoclax PO QD on days 1-28, azacitidine IV or SC on days 1-7, and pevonedistat IV over 60 minutes on days 1, 3, and 5. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Azacitidine

2012

Completed Phase 3

~1440

Pevonedistat

2021

Completed Phase 3

~770