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B-cell lymphoma-2 (BCL-2) inhibitor

Venetoclax + Chemotherapy for Acute Myeloid Leukemia

Phase 3
Recruiting
Led By Seth Karol, MD
Research Sponsored by LLS PedAL Initiative, LLC
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
- Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors) before start of protocol treatment.
-- Normal serum creatinine based on age/sex
Must not have
No known human immunodeficiency virus (HIV) infection.
- to participants with CD33 negative leukemic blasts (determined at local lab)
Timeline
Screening 3 weeks
Treatment Varies
Follow Up up to 5 years
Awards & highlights
No Placebo-Only Group
Pivotal Trial

Summary

This trial is testing whether adding venetoclax to standard chemotherapy can help young patients with relapsed AML. Venetoclax works by blocking a protein that helps cancer cells survive, making it easier for the chemotherapy to kill them. The study aims to find better treatment options for these patients who have limited choices. Venetoclax has been shown to improve overall survival in older and unfit patients with newly diagnosed acute myeloid leukemia when combined with lower intensity therapies.

Who is the study for?
This trial is for children and young adults aged up to 21 with relapsed Acute Myeloid Leukemia (AML) who can't receive more anthracyclines or are in their second relapse. They should be generally fit, have recovered from previous cancer treatments, not have certain conditions like Down syndrome or active infections, and must not be on medications that could interfere with the study drugs.
What is being tested?
The trial tests if adding venetoclax to a chemo mix of fludarabine/cytarabine/gemtuzumab ozogamicin improves survival in young AML patients at first or second relapse. It's randomized, meaning participants are put into groups by chance to compare different treatment combinations.
What are the potential side effects?
Possible side effects include low blood counts leading to increased infection risk, bleeding problems, liver issues due to drug interactions, allergic reactions to medication components, and potential heart complications. The severity of side effects can vary among individuals.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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It has been over 21 days since I last received interleukins, interferons, or cytokines treatment.
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My kidney function tests are normal for my age and sex.
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It's been over 42 days since I had any cell therapy, like T cell or NK cell treatment.
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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 not currently on medications like cyclosporine or tacrolimus for post-transplant care.
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It's been over 14 days since my last long-acting growth factor dose or over 7 days for a short-acting one.
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It has been more than 42 days since my last major bone marrow radiation.
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I am fit enough for another intensive chemotherapy as this is my second relapse.
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I have never needed treatment for heart failure.
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My leukemia does not have the FLT3/ITD mutation.
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I am between 29 days and 21 years old.
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I do not have active symptoms of graft versus host disease.
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I have never had severe liver blockage diseases or leukemia with CD33 negative cells.
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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 have been treated with venetoclax before.
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I do not have heart failure symptoms at my cancer's return.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I do not have HIV.
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My leukemia does not show CD33 on tests.
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I should not receive gemtuzumab ozogamicin.
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I have never had a severe case of VOD/SOS.
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I do not have an active, uncontrolled infection.
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I am a woman who has started menstruating and I have a positive pregnancy test.
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I cannot take medications by mouth due to a digestive condition.
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I have been diagnosed with APL or JMML.
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My cancer has spread to my brain but is limited or causing symptoms.
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I have a known congenital bone marrow failure syndrome.
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I haven't taken strong medications like rifampin or St. John's wort in the last week.
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I have had a severe liver condition after a transplant.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~up to 5 years
This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

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%
0%
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.
Pivotal Trial
The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups
Experimental Treatment
Active Control
Group I: Arm B: Experimental Arm with VenetoclaxExperimental Treatment5 Interventions
During cycle 1 (each cycle is 42 days), participants will receive 300 mg adult dose equivalent of venetoclax once on Day 1 followed by 600 mg adult dose equivalent of venetoclax on Days 2-21. Participants will also receive 30 mg/m\^2 of fludarabine followed by 2 g/m\^2 of cytarabine on Days 8-12. Gemtuzumab 3 mg/m\^2 will be given on Day 13 (only for participants with CD33 expression on leukemia blasts). During cycle 2, participants will receive 600 mg adult dose equivalent of venetoclax on Days 1-21. Participants will receive 30 mg/m\^2 of fludarabine followed by 2 g/m\^2 of cytarabine on Days 1-5. After cycle 2 participants are assessed for HSCT or azacitidine maintenance therapy in combination with venetoclax.
Group II: Arm A: Control Arm without VenetoclaxActive Control4 Interventions
During cycle 1 (each cycle is 42 days), participants will receive 30 mg/m\^2 of fludarabine followed by 2 g/m\^2 of cytarabine on Days 1-5. Gemtuzumab 3 mg/m\^2 will be given on Day 6 (only for participants with CD33 expression on leukemia blasts). During cycle 2 participants will receive 30 mg/m\^2 of fludarabine followed by 2 g/m\^2 of cytarabine on Days 1-5. After cycle 2 participants are assessed for hematopoietic stem cell transplantation (HSCT) or azacitidine maintenance therapy.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Cytarabine
2016
Completed Phase 3
~3330
Venetoclax
2019
Completed Phase 3
~2200
Gemtuzumab Ozogamicin
2006
Completed Phase 4
~440
Fludarabine
2012
Completed Phase 4
~1860
Azacitidine
2012
Completed Phase 3
~1440

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.
Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
Common treatments for Acute Myeloid Leukemia (AML) include Venetoclax, which inhibits the BCL-2 protein to promote apoptosis in cancer cells, and intensive combination chemotherapy, which targets rapidly dividing cells. Hypomethylating agents like azacitidine and decitabine interfere with DNA methylation to reactivate tumor suppressor genes. These treatments are vital for reducing leukemic cell burden, achieving remission, and improving survival rates in AML patients.
Synergistic effect of chidamide and venetoclax on apoptosis in acute myeloid leukemia cells and its mechanism.Maximal Activation of Apoptosis Signaling by Cotargeting Antiapoptotic Proteins in BH3 Mimetic-Resistant AML and AML Stem Cells.

Find a Location

Who is running the clinical trial?

EuPALUNKNOWN
Roche-GenentechIndustry Sponsor
25 Previous Clinical Trials
3,640 Total Patients Enrolled
Princess Maxima Center for Pediatric Oncology (European Sponsor)UNKNOWN

Media Library

Venetoclax (B-cell lymphoma-2 (BCL-2) inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT05183035 — Phase 3
Acute Myeloid Leukemia Research Study Groups: Arm A: Control Arm without Venetoclax, Arm B: Experimental Arm with Venetoclax
Acute Myeloid Leukemia Clinical Trial 2023: Venetoclax Highlights & Side Effects. Trial Name: NCT05183035 — Phase 3
~51 spots leftby Feb 2027