Pitavastatin + Venetoclax for CLL and AML

Overseen By Chao Family Comprehensive Cancer Center University of California, Irvine

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, Irvine

Must be taking: Venetoclax

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Prior venetoclax, CNS leukemia, 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: 1

Duration: 28 days per cycle, up to 2 years

6 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing the safety of combining Pitavastatin and Venetoclax in patients with certain types of leukemia who can't have intensive chemotherapy or whose cancer has come back or not responded to treatment. Pitavastatin may help fight cancer, and Venetoclax kills cancer cells by blocking a protein they need. Venetoclax is used to treat lymphomas and leukemias, but it has significant side effects.

Do I have to stop taking my current medications for the trial?

If you are currently taking a statin for cholesterol, you will need to stop it at least 72 hours before starting the trial. Other medications may need to be reviewed for interactions, especially those affecting CYP3A4, but the protocol does not specify stopping them.

What data supports the effectiveness of the drug Venetoclax for treating CLL and AML?

Venetoclax is effective for chronic lymphocytic leukemia (CLL), achieving response rates of about 80% in relapsed or refractory cases and is approved for use in combination with other drugs for both CLL and acute myeloid leukemia (AML). It has shown to prolong progression-free survival and induce undetectable minimal residual disease in CLL, and is approved for AML in patients who cannot undergo intensive chemotherapy. ^{1 2 3 4 5}

Is the combination of Pitavastatin and Venetoclax safe for humans?

Venetoclax, also known as Venclexta, has been shown to have an acceptable safety profile in patients with chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML), though it can cause side effects like neutropenia (low white blood cell count) and gastrointestinal issues. These side effects are generally manageable with supportive care and dose adjustments. ^{1 2 3 4 5}

How is the drug Pitavastatin + Venetoclax unique for treating CLL and AML?

The combination of Pitavastatin and Venetoclax is unique because Venetoclax is a first-in-class, oral drug that specifically targets and inhibits the BCL-2 protein, which helps cancer cells survive. This combination could potentially enhance the effectiveness of Venetoclax in treating chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) by adding Pitavastatin, although the specific benefits of this combination are still under investigation. ^{1 2 3 4 5}

Research Team

Elizabeth Brem, MD

Principal Investigator

Chao Family Comprehensive Cancer Center

Eligibility Criteria

Adults diagnosed with chronic lymphocytic leukemia (CLL) or acute myeloid leukemia (AML), including those new to AML treatment but ineligible for intensive chemotherapy, and patients with relapsed/refractory CLL. Participants must have stable organ function, not be on other statins, agree to use contraception if of childbearing potential, and be able to swallow pills.

Inclusion Criteria

My leukemia is confirmed and I am eligible for VEN therapy.

My CLL has come back or didn't respond to treatment, and I can take VEN alone or with rituximab.

I am newly diagnosed with AML and cannot undergo intensive chemotherapy due to age or health issues.

Exclusion Criteria

I can swallow pills without difficulty.

I do not have active hepatitis B or C, or I am successfully treated with no drug interactions.

I haven't taken strong CYP3A4 drugs in the last week.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Pitavastatin in combination with Venetoclax, with dose escalation to determine safety and tolerability

28 days per cycle, up to 2 years

Cycle 1 Day 1 Pre-PIT dose and predose Cycle 1 Day 2

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pitavastatin
• Venetoclax

Trial Overview This phase I trial is testing the safety of combining Pitavastatin with Venetoclax in treating CLL or AML. It's an open-label study where doses are increased gradually to find the highest dose patients can tolerate without severe side effects.

Participant Groups

Group I: Dose Level 2 (DL2) Experimental Treatment 2 Interventions

Patients receive Pitavastatin (PIT) 4 mg PO daily. For CLL patients, they will also receive stabilized Venetoclax (VEN) 400mg PO daily. For AML patients, they will VEN mg PO daily when dosing in combination with azacitidine or decitabine. If DL1 is well tolerated, the next cohort will progress to this dose level.

Group II: Dose Level 1 (DL1) Experimental Treatment 2 Interventions

Patients receive Pitavastatin (PIT) 2 mg PO daily. For CLL patients, they will also receive stabilized Venetoclax (VEN) 400mg PO daily. For AML patients, they will VEN mg PO daily when dosing in combination with azacitidine or decitabine. This is the starting dose level for the study.

Group III: Dose Level -1 (DL-1) Experimental Treatment 2 Interventions

Patients receive Pitavastatin (PIT) 1 mg PO daily. For CLL patients, they will also receive stabilized Venetoclax (VEN) 400mg PO daily. For AML patients, they will VEN mg PO daily when dosing in combination with azacitidine or decitabine. The 1 mg/day dose level will be held in reserve to allow dose reduction in those patients who cannot tolerate DL1.

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?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

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]

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]

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]

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]

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

3. France pubmed.ncbi.nlm.nih.gov

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

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

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

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

Venetoclax: First Global Approval. [2018]