What side effects are associated with this type of intervention?

Common treatments for Chronic Lymphocytic Leukemia (CLL) include Venetoclax, often used in combination with other agents like obinutuzumab. The primary side effects of Venetoclax include prolonged cytopenias, febrile neutropenia, mild to moderate gastrointestinal effects (such as nausea, vomiting, and diarrhea), fatigue, and edema. It should be used with caution in patients with liver disease, renal dysfunction, or those receiving CYP3A inhibitors. Other treatments like BTK inhibitors (e.g., ibrutinib, acalabrutinib) can cause side effects such as atrial fibrillation, bleeding, and hypertension. The combination of these therapies aims to balance efficacy with manageable toxicity profiles.

What prior FDA approvals exist?

Venetoclax, a BCL-2 inhibitor, has been approved by the FDA for use in combination with agents like obinutuzumab and rituximab for treating Chronic Lymphocytic Leukemia (CLL). Other targeted therapies, such as Bruton tyrosine kinase (BTK) inhibitors including ibrutinib and acalabrutinib, have also received FDA approval for CLL treatment. These approvals reflect the trend towards using targeted therapies in managing CLL.

What other types of research exist?

Promising novel alternatives to Pitavastatin and Venetoclax for CLL patients include Bruton tyrosine kinase (BTK) inhibitors such as acalabrutinib and zanubrutinib, which are noted for their efficacy and tolerability. Additionally, the combination of ibrutinib plus venetoclax has shown improved progression-free survival and rates of undetectable minimal residual disease. These alternatives offer targeted approaches with potential for better outcomes in CLL treatment.

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BCL-2 Inhibitor

Pitavastatin + Venetoclax for CLL and AML

Phase 1

Waitlist Available

Led By Elizabeth Brem, MD

Research Sponsored by University of California, Irvine

Eligibility Criteria Checklist

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

Must have

Pathologically confirmed AML or CLL, otherwise eligible for VEN-containing therapy at Screening

Relapsed/refractory CLL eligible to receive single-agent VEN or VEN in combination with rituximab at Screening.

Must not have

Patients who are unable to swallow pills are excluded.

Patients with acute promyelocytic leukemia are excluded

Timeline

Screening 3 weeks

Treatment Varies

Follow Up samples will be collected at the following timepoints: pre-ven dose during screening, cycle 1 day 1 pre-ven and pit dose, cycle 1 day 1 post dose sampling at 1, 2, 4, 8, 24 hours after first pit dose. each cycle is 28 days.

Awards & highlights

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include liver issues due to elevated enzymes, digestive problems from oral administration difficulties, muscle pain as a common statin issue, blood cell count changes affecting immunity and clotting risk increase.

Eligibility Criteria

Inclusion Criteria

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

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

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

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I stopped my statin medication 72 hours before starting VEN-based therapy.

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I have been on a stable dose of VEN for at least 5 days before starting PIT therapy.

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I have recently been diagnosed with CLL and can be treated with VEN and obinatuzumab.

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I agree to use birth control and not donate sperm for 90 days after my last dose.

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I am 18 years old or older.

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I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

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

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I can swallow pills without difficulty.

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I do not have acute promyelocytic leukemia.

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I do not have any severe ongoing illnesses that could interfere with the study.

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My leukemia has not spread to my brain or spinal cord.

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I have been treated with VEN before.

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I can take medications by mouth without issues.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ samples will be collected at the following timepoints: pre-ven dose during screening, cycle 1 day 1 pre-ven and pit dose, cycle 1 day 1 post dose sampling at 1, 2, 4, 8, 24 hours after first pit dose. each cycle is 28 days.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~samples will be collected at the following timepoints: pre-ven dose during screening, cycle 1 day 1 pre-ven and pit dose, cycle 1 day 1 post dose sampling at 1, 2, 4, 8, 24 hours after first pit dose. each cycle is 28 days.

This trial's timeline: 3 weeks for screening, Varies for treatment, and samples will be collected at the following timepoints: pre-ven dose during screening, cycle 1 day 1 pre-ven and pit dose, cycle 1 day 1 post dose sampling at 1, 2, 4, 8, 24 hours after first pit dose. each cycle is 28 days. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Complete Response Rate

Identifying Dose Limiting Toxicities (DLTs) for PIT administered with VEN-containing SOC regimens

Identifying overall Adverse Event Profile of PIT when given with VEN-containing SOC regimens

+2 more

Secondary study objectives

Number of Participants with Abnormal Laboratory Values and/or Adverse Events that Are Related to Treatment

Partial Response Rates

Percentage of Responders

+2 more

Other study objectives

Composite of PK parameters of VEN and PIT summarized by PIT dose level

Composite of dynamic BH3 profiling in priming of ex vivo AML and CLL specimens

Side effects data

From 2013 Phase 4 trial • 252 Patients • NCT01301066

Headache

Upper abdominal pain

Blood CK increased

Diarrhoea

Fatigue

Enterovesical fistula

Diverticulitis

Atrial septal defect

Transient ischaemic attack

Multiple fractures

Respiratory failure

Chronic obstructive pulmonary disease

Chest pain

Gastroenteritis

Gastroenteritis viral

Herpes dermatitis

Nausea

100%

80%

60%

40%

20%

Study treatment Arm

Pitavastatin 4 mg QD

Pravastatin 40 mg QD

Trial Design

3Treatment groups

Experimental Treatment

Group I: Dose Level 2 (DL2)Experimental Treatment2 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 Treatment2 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 Treatment2 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pitavastatin

FDA approved

Venetoclax

FDA approved

0 / 14Eligibility 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

Pitavastatin, an HMG-CoA Reductase Inhibitor, primarily lowers cholesterol but may also inhibit cancer cell proliferation and induce apoptosis. Venetoclax, a BCL-2 Inhibitor, targets the BCL-2 protein that helps cancer cells survive, promoting their apoptosis. These mechanisms are important for CLL patients as they offer targeted approaches to kill cancer cells, potentially improving disease management and outcomes.