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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for individuals with early-stage chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who do not yet show symptoms. The trial combines lenalidomide (also known as Revlimid), which may block cancer growth and boost the immune system, with a vaccine to determine if they can better combat cancer cells together. Two treatment groups exist: one receives the drug and vaccine simultaneously, while the other receives them in sequence. Individuals diagnosed with CLL or SLL, possessing specific genetic traits, and who have not yet received treatment may be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that lenalidomide, the treatment under study for chronic lymphocytic leukemia (CLL), presents some safety concerns. Studies have found a higher risk of death in CLL patients taking lenalidomide compared to those who do not. However, long-term research indicates that combining lenalidomide with rituximab leads to high response rates in CLL patients without significant safety issues. This suggests lenalidomide can be effective, but serious risks must be considered.

The trial uses the vaccine PCV13, which is generally safe. Pneumococcal vaccines like PCV13 have been safely used for a long time to prevent infections. Most side effects are mild, such as pain at the injection site or a slight fever, and serious side effects are rare.

Overall, lenalidomide presents some safety concerns, while the vaccine is considered safe. Participants should weigh the potential benefits against these risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Chronic Lymphocytic Leukemia (CLL) because they combine lenalidomide, an immunomodulatory drug, with the PCV13 vaccine to potentially enhance the immune response. Unlike standard CLL treatments, which typically focus on chemotherapy or targeted therapies like BTK inhibitors, these investigational approaches explore the synergy between a low-dose chemotherapy agent and a vaccine. This combination could uniquely stimulate the body's immune system to fight cancer cells more effectively. The innovative use of a vaccine in conjunction with lenalidomide offers a novel mechanism of action that could lead to better disease control and fewer side effects compared to current therapies.

What evidence suggests that this trial's treatments could be effective for chronic lymphocytic leukemia?

Studies have shown that lenalidomide effectively treats chronic lymphocytic leukemia (CLL). Patients using lenalidomide have managed to prevent their CLL from worsening for years. It strengthens the immune system and cuts off the blood supply to cancer cells. In this trial, participants will receive either concurrent or sequential administration of the pneumococcal conjugate vaccine (PCV13) with lenalidomide. Research suggests that combining PCV13 with lenalidomide can generate a strong immune response in CLL patients. This combination aims to help the body fight cancer cells more effectively. ^{1 3 5 6 7}

Who Is on the Research Team?

Kerry Rogers

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3407617/

Lenalidomide in the Treatment of Chronic Lymphocytic ... This article will provide a comprehensive summary regarding mechanism of action, efficacy and safety of lenalidomide in CLL patients. Relevant clinical trials ...

2. cllsociety.org cllsociety.org/2024/07/long-term-outcoes-after-lenalidomide-plus-rituximab-for-cll/

Long-term Outcomes After Lenalidomide plus Rituximab for ... Ten-year follow-up data showed that lenalidomide plus rituximab produced high response rates in patients with CLL with no significant safety signals.

3. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/3272/498944/Extended-Follow-up-of-a-Phase-2-Study-of-Early

Extended Follow up of a Phase 2 Study of Early Intervention ... Lenalidomide (LEN) is an effective therapy for chronic lymphocytic leukemia (CLL) and has immunomodulatory effects that were hypothesized to ...

4. healthtree.org healthtree.org/cll/community/articles/ash-23-lenalidomide-as-a-cll-treatment

ASH 2023: Lenalidomide as a CLL Treatment Study Findings. The results from the study showed: Many patients limited their CLL from progressing for years using lenalidomide. Using ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00267059

Lenalidomide (Revlimid) in Chronic Lymphocytic Leukemia ... Lenalidomide is designed to change the body's immune system and may also interfere with the development of tiny blood vessels that help support tumor growth ...

6. revlimid.com revlimid.com/

REVLIMID® (lenalidomide) - Official Patient Website Increased risk of death in people who have chronic lymphocytic leukemia (CLL). People with CLL who take REVLIMID have an increased risk of death compared with ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00963105

NCT00963105 | Study of Lenalidomide to Evaluate Safety ... The purpose of this study is to determine the safety and effectiveness of different dose regimens of lenalidomide in patients with relapsed or refractory ...