What side effects are associated with this type of intervention?

Common side effects of Venetoclax, especially when combined with chemotherapy for treating Acute Lymphoblastic Leukemia (ALL), include prolonged cytopenias (low blood cell counts), febrile neutropenia (fever with low neutrophil count), and gastrointestinal issues such as nausea, vomiting, and diarrhea. Other side effects may include fatigue, edema, and potential liver and renal dysfunction. Standard chemotherapy regimens for ALL can also cause similar side effects, including myelosuppression, increased risk of infections, and organ toxicity. Monitoring and supportive care are essential to manage these adverse effects.

What prior FDA approvals exist?

The FDA has approved several treatments for Acute Lymphoblastic Leukemia (ALL), including targeted therapies and chemotherapy regimens. Venetoclax, a BCL-2 inhibitor, is currently being studied in combination with chemotherapy for newly diagnosed ALL. Other FDA-approved treatments for ALL include tyrosine kinase inhibitors like imatinib and dasatinib for Philadelphia chromosome-positive ALL, and monoclonal antibodies such as blinatumomab and inotuzumab ozogamicin. These treatments aim to target specific pathways or markers on leukemia cells, similar to the approach being studied with Venetoclax.

What other types of research exist?

Promising novel alternatives to Venetoclax for ALL patients include: 1) Ponatinib combined with hyper-CVAD for Philadelphia chromosome-positive ALL, which has shown potential as a new standard of care. 2) Dasatinib combined with Blinatumomab for Ph-positive ALL, which has demonstrated efficacy in clinical studies. 3) Inotuzumab Ozogamicin for relapsed or refractory B-cell ALL, which has shown significant activity in both pediatric and adult patients. 4) ABT-737, a BH3-mimetic that inhibits antiapoptotic Bcl-2 family proteins, enhancing the cytotoxicity of standard chemotherapy agents like vincristine, dexamethasone, and L-asparaginase.

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BCL-2 Inhibitor

Venetoclax + Chemotherapy for Acute Lymphoblastic Leukemia

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

The most common treatments for Acute Lymphoblastic Leukemia (ALL) include chemotherapy and targeted therapies. Chemotherapy agents, such as methotrexate, vincristine, and prednisone, work by interfering with DNA replication and cell division, leading to the death of rapidly dividing leukemia cells. Venetoclax, a BCL-2 inhibitor, specifically targets the BCL-2 protein that helps cancer cells survive by preventing apoptosis (programmed cell death). By inhibiting BCL-2, Venetoclax promotes the death of leukemia cells. These treatments are crucial for ALL patients as they aim to reduce the leukemia cell population, achieve remission, and prevent relapse by targeting both the bulk of leukemia cells and the minimal residual disease that can lead to recurrence.

Phase < 1

Waitlist Available

Led By Jae Park, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

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

Must have

ECOG performance status of 0-2

Age 18-60

Must not have

Patients with HIV or active hepatitis B or hepatitis C infection are ineligible

CML in lymphoid blast crisis, mature B-cell (i.e. Burkitt's) lymphoma or mixed phenotype acute leukemia (MPAL)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing if adding venetoclax to standard chemotherapy is safe and effective for adults under 60 with newly diagnosed T- or B-cell acute lymphoblastic leukemia (ALL). Venetoclax helps chemotherapy work better by blocking a protein that keeps cancer cells alive. Venetoclax has shown promise in treating various forms of leukemia, including acute lymphoblastic leukemia (ALL), by enhancing the effectiveness of chemotherapy.

Who is the study for?

Adults aged 18-60 with newly diagnosed acute lymphoblastic leukemia (ALL), either T-cell or B-cell type, but without Philadelphia chromosome positive status. Participants must have good performance status, adequate kidney and liver function, and no active heart disease or other cancers. Pregnant women are excluded, and effective contraception is required.

What is being tested?

The trial tests the safety and effectiveness of Venetoclax combined with standard chemotherapy in treating adults with newly diagnosed ALL. The goal is to determine if this combination improves outcomes compared to traditional treatments alone.

What are the potential side effects?

Venetoclax may cause side effects such as nausea, diarrhea, low blood cell counts increasing infection risk, fatigue, potential liver issues indicated by abnormal blood tests, and possibly allergic reactions.

Eligibility Criteria

Inclusion Criteria

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

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

Select...

I am between 18 and 60 years old.

Select...

My kidneys are working well.

Select...

My lymphoma does not affect my bone marrow.

Select...

I have been newly diagnosed with a type of leukemia that is not associated with the Philadelphia chromosome.

Exclusion Criteria

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

Select...

I do not have HIV, hepatitis B, or hepatitis C.

Select...

My condition is either CML in lymphoid blast crisis, Burkitt's lymphoma, or MPAL.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

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%

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: Venetoclax in Combination With ChemotherapyExperimental Treatment1 Intervention

All patients will complete Induction I and II of the treatment regimens, consisting of several chemotherapy agents including Peg-ASP.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Venetoclax

2019

Completed Phase 3

~2240

0 / 7Eligibility 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

The most common treatments for Acute Lymphoblastic Leukemia (ALL) include chemotherapy and targeted therapies. Chemotherapy agents, such as methotrexate, vincristine, and prednisone, work by interfering with DNA replication and cell division, leading to the death of rapidly dividing leukemia cells. Venetoclax, a BCL-2 inhibitor, specifically targets the BCL-2 protein that helps cancer cells survive by preventing apoptosis (programmed cell death). By inhibiting BCL-2, Venetoclax promotes the death of leukemia cells. These treatments are crucial for ALL patients as they aim to reduce the leukemia cell population, achieve remission, and prevent relapse by targeting both the bulk of leukemia cells and the minimal residual disease that can lead to recurrence.

Venetoclax responses of pediatric ALL xenografts reveal sensitivity of MLL-rearranged leukemia.