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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of adding Pitavastatin to Venetoclax (a targeted therapy) for treating certain types of leukemia, specifically chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). The goal is to evaluate the effectiveness of this combination for individuals who cannot undergo intense chemotherapy or whose CLL has returned or resisted other treatments. It suits those already taking Venetoclax and diagnosed with CLL or AML, particularly if they cannot tolerate strong chemotherapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Venetoclax is generally safe for people with chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). It is already approved for these conditions, indicating thorough study. Most people tolerate it well.

The new aspect of this trial involves adding Pitavastatin to Venetoclax. Currently, little information exists on the safety of this combination. This trial is in its early stages, focusing mainly on assessing the safety of the combination in humans. The trial will start with low doses and gradually increase them to evaluate tolerance.

In short, Venetoclax is known to be safe, but the safety of the Pitavastatin-Venetoclax combination is still under investigation. Participation will help researchers learn more about how people respond to it. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Pitavastatin and Venetoclax for treating chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) because this approach targets cancer cells in a new way. Most treatments for these conditions focus on traditional chemotherapy or monoclonal antibodies. However, Venetoclax works by specifically inhibiting the BCL-2 protein, which helps cancer cells survive, while Pitavastatin might enhance this effect by altering cholesterol metabolism pathways in cancer cells. This combination could potentially lead to more effective cancer cell death and offer a promising alternative for patients who may not respond well to existing therapies.

What evidence suggests that this trial's treatments could be effective for CLL and AML?

Research has shown that adding pitavastatin to venetoclax treatment can help fight leukemia. In this trial, participants with chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) will receive varying doses of pitavastatin alongside venetoclax. In some patients, a single dose of pitavastatin lowered leukemia levels. Pitavastatin weakens cancer cells and makes them more sensitive to venetoclax, which then targets and kills these cells. It also enhances venetoclax's effectiveness by overcoming resistance. These findings offer hope that combining these drugs could benefit patients with CLL and AML. ^{2 5 6 7 8}

Who Is on the Research Team?

Elizabeth Brem, MD

Principal Investigator

Chao Family Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04512105

Study Details | NCT04512105 | Pitavastatin in Combination ... This is a phase I, dose-escalation, open-label clinical trial determining the safety and tolerability of adding Pitavastatin to Venetoclax in subjects with ...

2. ashpublications.org ashpublications.org/bloodneoplasia/article/1/4/100036/517602/A-phase-1-study-adding-pitavastatin-to-venetoclax

A phase 1 study adding pitavastatin to venetoclax therapy in ... Figure 1. Correlative studies suggest that pitavastatin reduces leukemia burden after a single dose in some patients. (A) Analysis of PBMCs ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124086427

Pitavastatin Potentiates Mitochondrial Dysfunction and ... PIT sensitizes AML cells to venetoclax by upregulating PUMA via a p53-independent mechanism and by reducing mitochondrial fitness.

4. biorxiv.org biorxiv.org/content/10.1101/2025.10.27.684888v1.full.pdf

Pitavastatin counteracts venetoclax resistance ... The BCL2 inhibitor venetoclax has therapeutic activity in several hematological malignancies. In acute myeloid leukemia (AML), venetoclax ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123125390

A Phase 1 Study of Adding Pitavastatin to Venetoclax ... We developed a phase 1 study of adding pitavastatin (PIT) to VEN-based therapy in patients with AML and CLL/small lymphocytic lymphoma (SLL)

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04512105

Pitavastatin in Combination With Venetoclax for Chronic ... This is a phase I, dose-escalation, open-label clinical trial determining the safety and tolerability of adding Pitavastatin to Venetoclax in subjects with ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2950328024000360

A phase 1 study adding pitavastatin to venetoclax therapy ... The 2 AML peripheral blood samples gave mixed results. In patient no. 1, VEN ramp-up eliminated most of the leukemia cells (7% vs 65% at baseline), and there ...

8. withpower.com withpower.com/trial/phase-1-leukemia-myeloid-11-2020-70452

Pitavastatin + Venetoclax for CLL and AML Venetoclax, also known as Venclexta, has been shown to have an acceptable safety profile in patients with chronic lymphocytic leukemia (CLL) and acute myeloid ...