What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML) include venetoclax, hypomethylating agents (HMAs) like azacitidine and decitabine, and combination chemotherapies. Venetoclax, often used in combination with other agents, can cause side effects such as neutropenia, diarrhea, and hypertension. HMAs, when combined with other agents, can lead to similar side effects including neutropenia, thrombocytopenia, infections, and tumor lysis syndrome (TLS). Combination chemotherapies, which may include drugs like cytarabine and idarubicin, can result in side effects such as myelosuppression, gastrointestinal symptoms, and increased risk of infections.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Acute Myeloid Leukemia (AML) that are similar to venetoclax, which inhibits BCL-2 to prevent cancer cell growth. Notably, hypomethylating agents (HMAs) such as azacitidine and decitabine are commonly used, often in combination with venetoclax. Azacitidine and decitabine work by inhibiting DNA methylation, leading to the reactivation of tumor suppressor genes. Additionally, ivosidenib and enasidenib, which target mutant IDH1 and IDH2 enzymes respectively, have also been approved for AML treatment. These drugs offer alternative mechanisms to disrupt cancer cell metabolism and growth.

What other types of research exist?

Promising novel alternatives to Venetoclax for AML patients include: 1) Gilteritinib, a second-generation FLT3 tyrosine kinase inhibitor, especially for patients with FLT3-ITD mutation. 2) Imetelstat, a telomerase inhibitor, which has shown partial and complete responses in advanced myelofibrosis, potentially applicable to AML. 3) Combination therapies such as FLAG-GO (fludarabine, cytarabine, granulocyte colony-stimulating factor, and gemtuzumab ozogamicin) and IA+V (idarubicin, high-dose cytarabine, and vorinostat) have also shown promise in clinical trials.

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Antimetabolite

Venetoclax + Chemotherapy for Acute Myeloid Leukemia

Q: What is the mechanism of action of this treatment?

Common treatments for Acute Myeloid Leukemia (AML) include Venetoclax, hypomethylating agents (HMAs) like azacitidine and decitabine, and FLT3 inhibitors. Venetoclax works by inhibiting the BCL-2 protein, essential for cancer cell survival, thereby inducing apoptosis. HMAs inhibit DNA methylation, reactivating tumor suppressor genes and leading to cancer cell death. FLT3 inhibitors target mutations in the FLT3 gene that drive AML cell proliferation. These treatments are vital for AML patients as they specifically target the survival and proliferation pathways of cancer cells, offering more effective and personalized treatment options.

Phase 1 & 2

Recruiting

Led By Courtney DiNardo

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

Only patients who are relapsed, refractory, or intolerant of standard AML therapy will be eligible for Part 1 (minimum of 1 prior line of AML-directed therapy)

Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

Must not have

Patients with known dysphagia, short-gut syndrome, or other conditions that would affect the ingestion or gastrointestinal absorption of drugs administered orally

Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British [FAB] class M3-AML)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 6 years

Awards & highlights

All Individual Drugs Already Approved

Approved for 5 Other Conditions

No Placebo-Only Group

Summary

This trial is testing venetoclax with chemotherapy drugs to treat patients with acute myeloid leukemia (AML). Venetoclax blocks enzymes needed for cancer cell growth, while the chemotherapy drugs kill or stop the spread of cancer cells. Venetoclax is a selective Bcl-2 inhibitor used for treating lymphomas and leukemias, including AML, and has shown improved outcomes when combined with other treatments.

Who is the study for?

This trial is for adults with newly diagnosed or stubborn acute myeloid leukemia (AML) who can perform daily activities with ease to moderate difficulty. They must have acceptable liver and kidney function, understand the study, and use effective contraception if needed. It's not for those with severe heart issues, trouble swallowing, prior BCL2 inhibitor therapy, certain genetic abnormalities in their leukemia, active infections like HIV or hepatitis B/C, or a very high white blood cell count.

What is being tested?

The trial is testing the effectiveness of Venetoclax combined with chemotherapy drugs (fludarabine, cytarabine, filgrastim and idarubicin) on AML patients. The goal is to find the best dose that works well together while monitoring side effects. This combination may be more effective than current treatments by blocking enzymes cancer cells need to grow.

What are the potential side effects?

Venetoclax and these chemotherapy drugs might cause fatigue; nausea; hair loss; increased risk of infection due to low blood cell counts; mouth sores; diarrhea; liver problems signaled by yellowing skin/eyes; easy bruising/bleeding from low platelets. Some side effects could be serious.

Eligibility Criteria

Inclusion Criteria

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

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My AML has not improved with standard treatments.

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I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

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

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I have a condition that affects my ability to swallow or absorb pills.

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My leukemia is of a specific type known as acute promyelocytic leukemia.

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I have previously received BCL2 inhibitor therapy.

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I have severe heart failure or my heart pumps less than 40% of the blood.

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I have had a heart attack in the last 6 months or have uncontrolled heart problems.

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I have HIV or active hepatitis B or C.

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I am not pregnant, using reliable birth control, or not of childbearing age.

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My acute myeloid leukemia (AML) has spread to my brain or spinal cord.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 6 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 6 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 6 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

Anti-tumor activity

CR/CRi rate

Drug exposure levels

+7 more

Secondary study objectives

Morphologic leukemia-free state

Other study objectives

Exploratory biomarkers

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

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

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, FLAG-IDA)Experimental Treatment6 Interventions

See detailed description.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cytarabine

FDA approved

Pegfilgrastim

FDA approved

Venetoclax

FDA approved

Filgrastim

FDA approved

Fludarabine

FDA approved

Idarubicin

FDA approved

0 / 10Eligibility criteria met

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, hypomethylating agents (HMAs) like azacitidine and decitabine, and FLT3 inhibitors. Venetoclax works by inhibiting the BCL-2 protein, essential for cancer cell survival, thereby inducing apoptosis. HMAs inhibit DNA methylation, reactivating tumor suppressor genes and leading to cancer cell death. FLT3 inhibitors target mutations in the FLT3 gene that drive AML cell proliferation. These treatments are vital for AML patients as they specifically target the survival and proliferation pathways of cancer cells, offering more effective and personalized treatment options.

Synergistic effect of chidamide and venetoclax on apoptosis in acute myeloid leukemia cells and its mechanism.AMG 176, a Selective MCL1 Inhibitor, Is Effective in Hematologic Cancer Models Alone and in Combination with Established Therapies.Targeted therapies in Acute Myeloid Leukemia: a focus on FLT-3 inhibitors and ABT199.