Combination Chemotherapy for Acute Lymphoblastic Leukemia

Overseen By Jain Nitin, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

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

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

26 Participants Needed

Trial Summary

What is the purpose of this trial?

The addition of ponatinib to mini-hyper-CVD chemotherapy and venetoclax will improve the complete remission rate in patients with relapsed or refractory T-cell acute lymphoblastic leukemia

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications or herbal supplements that strongly affect the liver enzyme CYP3A4 at least 7 days before starting ponatinib or within 3 days of starting venetoclax. You should also avoid consuming grapefruit, Seville oranges, or star fruit within 3 days before starting venetoclax.

What data supports the effectiveness of the drug Venetoclax for treating acute lymphoblastic leukemia?

Venetoclax has shown promise in treating relapsed T-cell acute lymphoblastic leukemia (T-ALL) by targeting proteins that help cancer cells survive, as seen in a case report where it was used successfully with another drug. Additionally, Venetoclax is effective in treating chronic lymphocytic leukemia (CLL), achieving high response rates and improving survival outcomes in combination with other treatments. ^{1 2 3 4 5}

Is the combination chemotherapy treatment generally safe for humans?

Venetoclax, a part of the combination chemotherapy, has been shown to have an acceptable safety profile in patients with chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). Common side effects include neutropenia (low white blood cell count) and gastrointestinal issues, but these can be managed with supportive care and dose adjustments. ^{1 2 3 5 6}

What makes the treatment Mini-hyper CVD, Ponatinib, Venetoclax unique for acute lymphoblastic leukemia?

This treatment is unique because it combines Venetoclax, a drug that targets and inhibits a protein called BCL-2 to help kill cancer cells, with other chemotherapy agents, offering a novel approach for patients with relapsed or refractory acute lymphoblastic leukemia who have limited treatment options. ^{1 2 4 5 7}

Research Team

Jain Nitin, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults with relapsed or refractory T-cell acute lymphoblastic leukemia who've had previous treatments, have a certain level of bone marrow involvement, and are in decent physical condition (ECOG ≤2). They must have proper liver and kidney function, not be pregnant or breastfeeding, agree to use contraception, and can't join if they have uncontrolled infections, recent heart issues, or other serious health problems.

Inclusion Criteria

Women of childbearing potential must have a negative pregnancy test result and agree to use effective contraception

My T-cell acute lymphoblastic leukemia has not responded to previous treatments.

Patients must provide written informed consent

Exclusion Criteria

I don't have any severe health or mental conditions that could affect the study.

I do not have severe heart disease.

I do not have uncontrolled heart or blood vessel problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Ponatinib Treatment

Participants receive ponatinib as a single agent for 3 days prior to chemotherapy

3 days

Chemotherapy

Participants receive mini-hyper-CVD chemotherapy in the inpatient setting, starting on day 1 of each cycle

Cycles 2-8

Venetoclax Treatment

Participants receive venetoclax 400mg daily on days 1-14 of each 28-day cycle

14 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Mini-hyper CVD
• Ponatinib
• Venetoclax

Trial Overview The trial is testing whether adding the drug Ponatinib to a combination of mini-hyper CVD chemotherapy and Venetoclax improves remission rates in patients with tough-to-treat T-cell acute lymphoblastic leukemia.

Participant Groups

Group I: Venetoclax Experimental Treatment 1 Intervention

Patients will continue venetoclax 400mg daily on days 1-14 of each 28-day cycle.

Group II: Ponatinib Experimental Treatment 1 Intervention

Participants will receive ponatinib (45mg daily) as a single agent for 3 days. These will be called Days -3, -2 and -1

Group III: Mini-hyper-CVD Experimental Treatment 1 Intervention

Chemotherapy will be administered in the inpatient setting, starting on day 1 of each of the cycles 2-8.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

Venetoclax is a highly effective treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), achieving response rates of about 80% in clinical trials involving 240 patients from 2011 to 2016.

While venetoclax has an acceptable safety profile, common side effects include neutropenia and diarrhea, and there is a risk of tumor lysis syndrome (TLS), which can be managed through careful dose ramp-up and patient education, leading to no reported TLS events in ongoing trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . Brumbaugh Paradis, H., Alter, D., Llerandi, D.[2018]

Venetoclax is an oral medication that selectively inhibits the BCL-2 protein, which helps cancer cells survive, thereby restoring the ability of these malignant cells to undergo programmed cell death (apoptosis).

It has been approved in the USA for treating chronic lymphocytic leukaemia (CLL) in patients with a specific genetic marker (17p deletion) who have already undergone at least one prior therapy, and it is being studied for various other blood cancers and conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: First Global Approval. Deeks, ED.[2018]

In the phase III CLL14 trial, a 12-month treatment with venetoclax combined with obinutuzumab significantly improved progression-free survival and rates of undetectable minimal residual disease compared to traditional chemoimmunotherapy with chlorambucil and obinutuzumab in patients with untreated chronic lymphocytic leukaemia.

Venetoclax + obinutuzumab is a well-tolerated, chemotherapy-free treatment option for CLL, with manageable side effects like neutropenia, making it suitable for patients who cannot undergo intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. Blair, HA.[2021]

A patient with relapsed T-cell acute lymphoblastic leukemia (T-ALL) showed a clinical response to venetoclax, an oral BCL-2 inhibitor, combined with a hypomethylating agent, highlighting a potential new treatment strategy for this challenging condition.

Given that less than 7% of patients with relapsed T-ALL achieve long-term survival, targeting antiapoptotic proteins like BCL-2 could offer a promising approach to improve outcomes in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax and decitabine for treatment of relapsed T-cell acute lymphoblastic leukemia: A case report and review of literature. Farhadfar, N., Li, Y., May, WS., et al.[2021]

Venetoclax is an effective oral treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), showing durable responses and a manageable safety profile in clinical trials, including patients with poor prognostic factors.

In combination with rituximab, venetoclax significantly improved progression-free survival and achieved undetectable minimal residual disease compared to bendamustine plus rituximab, with benefits lasting for at least 36 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. Scott, LJ.[2020]

Venetoclax is an effective oral medication for treating chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML), showing significant efficacy when combined with other therapies like obinutuzumab and azacitidine.

While venetoclax is associated with adverse events such as neutropenia and gastrointestinal disorders, the article emphasizes the importance of managing these side effects to ensure patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical Management of the Venetoclax-Treated Patient in Chronic Lymphocytic Leukemia and Acute Myeloid Leukemia. Waggoner, M., Katsetos, J., Thomas, E., et al.[2022]

In a study of 15 patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL), Venetoclax combined with multidrug chemotherapy resulted in a 67.7% overall response rate and a 60% complete response rate, indicating significant efficacy.

The treatment was found to be safe, with manageable hematological toxicities and no severe adverse reactions, suggesting that Venetoclax combined with chemotherapy could be a promising option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical efficacy and safety of venetoclax combined with multidrug chemotherapy in the treatment of 15 patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia]. Kong, JY., Zong, LH., Pu, Y., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Venetoclax: First Global Approval. [2018]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. [2021]

4. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Venetoclax and decitabine for treatment of relapsed T-cell acute lymphoblastic leukemia: A case report and review of literature. [2021]

5. France pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Practical Management of the Venetoclax-Treated Patient in Chronic Lymphocytic Leukemia and Acute Myeloid Leukemia. [2022]

7. China pubmed.ncbi.nlm.nih.gov

[Clinical efficacy and safety of venetoclax combined with multidrug chemotherapy in the treatment of 15 patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia]. [2023]