Venetoclax + Chemotherapy for Acute Lymphoblastic Leukemia

Overseen By Mark Geyer, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: CYP3A inducers

Disqualifiers: CML, HIV, Hepatitis B/C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding venetoclax to standard chemotherapy is safe and effective for adults newly diagnosed with acute lymphoblastic leukemia (ALL), a type of blood cancer. Participants will receive a combination of venetoclax and several chemotherapy drugs. It targets adults under 60 with a specific type of ALL involving T-cells or B-cells. Those without prior ALL treatments and with normal kidney and liver function may be suitable candidates. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken strong or moderate CYP3A inducers within 7 days before starting the study treatment. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that combining venetoclax with chemotherapy is likely to be safe for adults with acute lymphoblastic leukemia?

Research has shown that venetoclax, when combined with chemotherapy, may help treat acute lymphoblastic leukemia (ALL). Previous studies tested this combination and found it effective against ALL, suggesting potential efficacy.

Regarding safety, some studies have reported mild side effects, such as small decreases in heart function observed in animal studies. However, overall, the combination has been manageable. In a study with adults, venetoclax with low-intensity chemotherapy produced side effects within expected limits.

If venetoclax is approved for another condition, it indicates some level of safety. However, this study is in the early stages. Early phase studies primarily focus on safety, so much remains to be learned about how well people tolerate this treatment. Participants in this trial will help researchers gather more information on its safety in adults with newly diagnosed ALL. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Venetoclax in combination with chemotherapy for acute lymphoblastic leukemia because it brings a new approach to treatment. Unlike standard chemotherapy treatments that broadly target rapidly dividing cells, Venetoclax specifically targets and inhibits a protein called BCL-2, which helps cancer cells survive. By blocking BCL-2, Venetoclax can make cancer cells more vulnerable to chemotherapy, potentially enhancing the effectiveness of treatment and leading to better outcomes for patients. This targeted mechanism of action sets Venetoclax apart from traditional treatments and offers hope for improved responses in patients with this aggressive cancer.

What evidence suggests that combining venetoclax with chemotherapy could be effective for acute lymphoblastic leukemia?

Research has shown that venetoclax, when combined with chemotherapy, might improve treatment outcomes for acute lymphoblastic leukemia (ALL). In this trial, all participants will receive venetoclax alongside chemotherapy. Studies have found that venetoclax, a drug that helps kill cancer cells, can enhance the effectiveness of chemotherapy. In other types of leukemia, venetoclax has already demonstrated positive results by targeting specific cancer cells and reducing the disease. Early findings suggest that this combination could also benefit adults newly diagnosed with ALL. ^{1 4 5 6 7}

Who Is on the Research Team?

Jae Park, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

My liver is functioning well, with specific blood test levels within acceptable ranges.

I have ALL with CNS involvement and can get additional treatments for it.

Exclusion Criteria

I don't have any active cancer needing treatment, except for minor skin cancers or cancers I've been free of for 5 years.

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

I haven't had a heart attack, stroke, or severe heart issues in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction I

Participants receive venetoclax and chemotherapy agents including Peg-ASP. Venetoclax dosing varies by dose level.

28 days

Multiple visits for treatment and monitoring

Induction II

Continuation of venetoclax and chemotherapy treatment. Venetoclax dosing varies by dose level.

42 days

Multiple visits for treatment and monitoring

Consolidation

Includes 2 Intensification blocks and 2 Re-Induction blocks with venetoclax and chemotherapy agents.

130 days

Multiple visits for treatment and monitoring

Maintenance

Participants receive a 4-drug regimen for 2 years. No venetoclax is administered during this phase.

2 years

Bone marrow aspirate and biopsy every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Venetoclax

Trial Overview 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.

How Is the Trial Designed?

Group I: Venetoclax in Combination With Chemotherapy Experimental Treatment 1 Intervention

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

Venetoclax is already approved in United States, European Union for the following indications:

Approved in United States as Venclexta for:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)
• Acute myeloid leukemia (AML)

Approved in European Union as Venclyxto for:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)
• Acute myeloid leukemia (AML)

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4654800/

ABT-199 (venetoclax) and BCL-2 inhibitors in clinical ... This review focused on the current clinical development of a highly effective class of small molecule BCL-2 inhibitors, including ABT-199/venetoclax.

2. ashpublications.org ashpublications.org/bloodadvances/article/9/3/617/525999/Venetoclax-plus-low-intensity-chemotherapy-for

Venetoclax plus low-intensity chemotherapy for adults with ... In acute lymphoblastic leukemia (ALL), the B-cell lymphoma 2 inhibitor venetoclax may enhance the efficacy of chemotherapy, allowing dose ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02203773

NCT02203773 | Study of ABT-199 (GDC-0199) in ... This is a Phase 1b, open-label, non-randomized, multicenter study to evaluate the safety and pharmacokinetics of orally administered venetoclax (ABT-199) ...

4. abbvie.com abbvie.com/content/dam/abbvie-dotcom/us/clinical-trials/venetoclax_M16-106.pdf

Venetoclax (ABT-199) M16-106 Clinical Study Report This was an open-label, Phase 1 dose escalation study in pediatric and adult subjects with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) or R/R ...

5. nature.com nature.com/articles/s41420-022-01009-1

The BCL-2 inhibitor ABT-199/venetoclax synergizes with ... ... ABT-199/Venetoclax showed efficacy in the treatment of chronic lymphocytic leukemia [6, 7]. ABT-199 is effective in hematopoietic ...

6. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/20/NCT02055820/Prot_002.pdf

A Phase IB/II, Open-Label Study Evaluating the Safety and In an anesthetized dog CV model given intravenous (IV) doses of venetoclax, mild reductions in cardiac output (−11% to −19%) and myocardial contractility (dP/ ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118474733

Safety and Efficacy of a Combination of Venetoclax (GDC ... We present preliminary efficacy and updated safety data from an ongoing phase 1b study (NCT01685892) evaluating this combination in R/R or treatment-naïve (TN) ...