Lenalidomide + Vaccine for Chronic Lymphocytic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, H2-blockers

Disqualifiers: Prior CLL/SLL treatment, Recent DVT/PE, Allergic reactions, Uncontrolled illness, 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

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

Compensation: Varies

Number of Visits: 4

Duration: 24 months

49 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies lenalidomide and a vaccine in patients with early-stage CLL or SLL. Lenalidomide stops cancer growth and boosts the immune system, while the vaccine helps the body fight infections. Together, they aim to improve the body's defense against cancer. Lenalidomide has been extensively studied and used in the treatment of various blood cancers due to its ability to promote tumor cell death and stimulate immune responses.

Will I have to stop taking my current medications?

The trial requires that you stop taking corticosteroids two weeks before starting, unless it's a low-dose maintenance therapy for a non-cancer condition. You also need to stop taking H2-blockers (like cimetidine or ranitidine) before starting the trial.

What data supports the effectiveness of the drug Lenalidomide for treating chronic lymphocytic leukemia?

Research shows that Lenalidomide, an oral drug that helps the immune system fight cancer, has been effective in treating chronic lymphocytic leukemia (CLL), especially in patients who have not responded to other treatments. It has shown promise both as a single treatment and when combined with other drugs like rituximab. ^{1 2 3 4 5}

Is the combination of Lenalidomide and vaccines safe for treating Chronic Lymphocytic Leukemia?

Lenalidomide, used in treating Chronic Lymphocytic Leukemia (CLL), can cause side effects like low white blood cell counts (neutropenia), low platelet counts (thrombocytopenia), and reactions like tumor flare and tumor lysis syndrome. While it shows promise in CLL, careful monitoring and management of these side effects are important for safe use. ^{3 6 7 8 9}

How is the drug Lenalidomide + Vaccine unique for treating chronic lymphocytic leukemia?

Lenalidomide is an oral drug that modifies the immune system and has shown promise in treating chronic lymphocytic leukemia (CLL) by potentially restoring immune function and improving disease outcomes. This treatment is unique because it combines lenalidomide with a vaccine, aiming to enhance the immune response in CLL patients who typically respond poorly to vaccines. ^{3 4 5 6 8}

Research Team

Kerry Rogers

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for patients with early-stage, asymptomatic chronic lymphocytic leukemia or small lymphocytic lymphoma who have high-risk genomic features but haven't had previous CLL/SLL treatments. Participants must be in good health with proper organ function and no history of certain conditions like uncontrolled illness or recent deep vein thrombosis.

Inclusion Criteria

I do not meet the criteria for starting treatment based on symptoms or previous therapies for CLL/SLL.

I have been diagnosed with CLL or SLL according to WHO standards.

My CLL/SLL cancer cells show high-risk genetic changes.

Exclusion Criteria

I have received treatment for my CLL/SLL before this study.

I haven't taken corticosteroids in the last two weeks, except for a non-cancer related condition.

Patients receiving other investigational agents

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive lenalidomide and PCV13 vaccine either concurrently or sequentially over 24 cycles

24 months

Monthly visits for treatment cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

Every 3 months for 1 year, then every 6 months

Treatment Details

Interventions

• Lenalidomide
• Pneumococcal Polyvalent Vaccine

Trial Overview The study tests the combination of lenalidomide, a drug that may inhibit cancer growth and stimulate the immune system, with a pneumococcal vaccine designed to boost the body's ability to fight cancer cells. The goal is to see if this combo can create a stronger immune response against cancer.

Participant Groups

Group I: Arm B (Sequential PCV13 and lenalidomide) Experimental Treatment 6 Interventions

Patients receive PCV13 IM on days 1 and 78 (cycles 1 and 3). Patients also receive low-dose lenalidomide as in arm 1 beginning on day 1 of course 4. Treatment repeats every 28 days for at least 24 cycles in the absence of disease progression or unacceptable toxicity. Patients may undergo bone marrow biopsy and aspirate and CT during screening and blood sample collection throughout the study. (Blood sample collection discontinued with approval of protocol version 24 dated 3/15/2024)

Group II: Arm A (Concurrent PCV13 and lenalidomide) Experimental Treatment 6 Interventions

Patients receive low-dose lenalidomide PO once daily on days 1-28. Treatment repeats every 28 days for at least 24 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive PCV13 IM on day 1 of courses 3 and 5. Patients may undergo bone marrow biopsy and aspirate and CT during screening and blood sample collection throughout the study. (Blood sample collection discontinued with approval of protocol version 24 dated 3/15/2024)

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

Approved in European Union as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Approved in United States as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase II trial involving 45 patients with relapsed or refractory chronic lymphocytic leukemia (CLL), lenalidomide demonstrated a 47% overall response rate, indicating its clinical activity in this difficult-to-treat population.

The most common side effects were fatigue, thrombocytopenia, and neutropenia, affecting 83%, 78%, and 78% of patients respectively, highlighting the need for monitoring and management of these adverse effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study. Chanan-Khan, A., Miller, KC., Musial, L., et al.[2022]

In a phase II study involving 59 adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL), the combination of lenalidomide and rituximab resulted in a 66% overall response rate, indicating significant efficacy as a salvage therapy.

While the treatment showed promise, it was associated with notable side effects, particularly neutropenia in 73% of patients, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of lenalidomide and rituximab as salvage therapy for patients with relapsed or refractory chronic lymphocytic leukemia. Badoux, XC., Keating, MJ., Wen, S., et al.[2021]

Lenalidomide shows distinct anti-tumor activity in chronic lymphocytic leukemia (CLL) compared to its approved uses in myelodysplastic syndromes and multiple myeloma, indicating a unique mechanism of action in this type of cancer.

The use of lenalidomide in CLL can lead to specific toxicities, such as tumor flare reactions and tumor lysis, even at low doses, which are not typically seen in its other approved indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide alone and in combination for chronic lymphocytic leukemia. Chen, CI.[2021]

Lenalidomide is an effective oral treatment for various hematologic malignancies, including chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), with different starting doses based on the type of cancer.

Common side effects like neutropenia and thrombocytopenia can be managed effectively with proper monitoring and prophylaxis, allowing for safer administration and improved patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approaches to Managing Safety With Lenalidomide in Hematologic Malignancies. Blumel, S., Broadway-Duren, J.[2020]

References

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

How does lenalidomide target the chronic lymphocytic leukemia microenvironment? [2021]

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

Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study. [2022]

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

Single-agent lenalidomide in the treatment of previously untreated chronic lymphocytic leukemia. [2021]

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

Phase II study of lenalidomide and rituximab as salvage therapy for patients with relapsed or refractory chronic lymphocytic leukemia. [2021]

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

Lenalidomide and rituximab for the initial treatment of patients with chronic lymphocytic leukemia: a multicenter clinical-translational study from the chronic lymphocytic leukemia research consortium. [2021]

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

Early Intervention with Lenalidomide in Patients with High-risk Chronic Lymphocytic Leukemia. [2023]

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

Safety and efficacy of different lenalidomide starting doses in patients with relapsed or refractory chronic lymphocytic leukemia: results of an international multicenter double-blinded randomized phase II trial. [2020]

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

Lenalidomide alone and in combination for chronic lymphocytic leukemia. [2021]

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

Approaches to Managing Safety With Lenalidomide in Hematologic Malignancies. [2020]