R-ICE + Lenalidomide for Refractory Large B-Cell Lymphoma

Not currently recruiting at 13 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Academic and Community Cancer Research United

Must be taking: Aspirin

Must not be taking: Antiretrovirals

Disqualifiers: Pregnancy, Active infection, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the optimal dose and safety of lenalidomide combined with a chemotherapy regimen known as R-ICE for treating diffuse large B-cell lymphoma. This condition involves cancerous B-cells that have either relapsed or are refractory. The trial aims to determine if this combination can more effectively halt cancer cell growth. Suitable participants have diffuse large B-cell lymphoma that hasn't responded to a single previous treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to contribute to groundbreaking research.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not be receiving any other treatment for lymphoma, and you should be at least 2 weeks from your last anti-lymphoma therapy. You can use steroids and rituximab up to 1 week before joining the trial for symptom management.

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

Research is testing the safety and effectiveness of adding lenalidomide to R-ICE, a chemotherapy combination, for patients with diffuse large B-cell lymphoma that has returned or not responded to treatment. Early results suggest this combination is generally well-tolerated.

Earlier studies have shown common side effects, including low blood cell counts, tiredness, and nausea. While these side effects can be uncomfortable, they are often manageable. Importantly, no unexpected or severe adverse events were reported, indicating a positive sign for the treatment's safety.

This trial is in both Phase 1 and Phase 2, meaning it is still under evaluation. Phase 1 focuses on safety and dosage, while Phase 2 examines effectiveness. Although early safety results are promising, more data will help confirm the treatment's safety and effectiveness for more patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for refractory large B-cell lymphoma, which often involve chemotherapy alone, this combination therapy incorporates lenalidomide, an immune-modulating drug. Researchers are excited because lenalidomide works by enhancing the body's immune response against cancer cells, potentially increasing the effectiveness of the traditional R-ICE chemotherapy regimen. Additionally, the treatment is structured in cycles that allow for flexibility based on patient response, enabling more personalized care. This innovative approach aims to improve outcomes by targeting the cancer more comprehensively.

What evidence suggests that this trial's treatments could be effective for large B-cell lymphoma?

Research has shown that adding lenalidomide to the R-ICE treatment, which participants in this trial will receive, holds promise for treating difficult or recurring diffuse large B-cell lymphoma. Patients who received this combination responded better than those who only received R-ICE. Studies indicate that lenalidomide can enhance the effectiveness of the chemotherapy drugs. R-ICE is already a known treatment, and adding lenalidomide may more effectively inhibit cancer cell growth and spread. This combination aims to attack the cancer in several ways, increasing the chances of shrinking tumors or stopping their growth. ^{1 2 3 4 6}

Who Is on the Research Team?

Grzegorz S Nowakowski

Principal Investigator

Academic and Community Cancer Research United

Are You a Good Fit for This Trial?

Adults with relapsed or refractory diffuse large B-cell lymphoma can join this trial. They must have measurable disease, be willing to take daily aspirin for blood clot prevention (or an alternative if allergic), and women of childbearing age need negative pregnancy tests and agree to use contraception. Participants should not have had more than one prior anti-lymphoma therapy and must be able to follow the study's requirements.

Inclusion Criteria

Females of reproductive potential are willing and able to adhere to the scheduled pregnancy testing as required by Celgene's REVLIMID REMS program

PHASE II: Subjects must have calculated creatinine clearance >= 30 ml/min by Cockcroft-Gault formula, obtained =< 7 days prior to registration

Willing to provide blood samples for correlative research purposes

Exclusion Criteria

I am HIV positive but not immunocompromised, or I am on certain HIV medications with a CD4 count over 400.

All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure

I am not willing to use birth control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lenalidomide orally daily on days 1-14, rituximab IV on day 1, ifosfamide IV over 24 hours on day 2, carboplatin IV over 1-2 hours on day 2, and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 cycles.

6 weeks

Multiple visits for IV administration

Extended Treatment

Participants achieving CMR, PMR, or NMR may receive 2 more cycles of treatment per physician discretion.

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 3 months for 3 years and then every 6 months for 2 years.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Etoposide
• Ifosfamide
• Lenalidomide
• Rituximab

Trial Overview The trial is testing the combination of lenalidomide with R-ICE chemotherapy (rituximab, ifosfamide, carboplatin, etoposide) in patients whose lymphoma has returned or didn't respond to initial treatment. It aims to find the safest dose of lenalidomide that works best when used with R-ICE.

How Is the Trial Designed?

Group I: Treatment (R2-ICE) Experimental Treatment 6 Interventions

Patients receive lenalidomide PO daily on days 1-14, rituximab IV on day 1, ifosfamide IV over 24 hours on day 2, carboplatin IV over 1-2 hours on day 2, and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients achieving CMR, PMR, or NMR may receive 2 more cycles per physician discretion. After completion of 2 cycles of R2ICE treatment, patients achieving objective status of CMR, PMR or NMR may proceed to SCT during the event monitoring phase.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Academic and Community Cancer Research United

Lead Sponsor

Trials

54

Recruited

4,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Lenalidomide is an orally bioavailable immunomodulator that has shown significant antitumor activity in treating various types of B-cell lymphomas, including mantle cell lymphoma and diffuse large B-cell lymphoma.

The drug has a favorable safety profile and is effective both as a standalone treatment and in combination with other therapies, marking a shift from traditional chemotherapy approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of lenalidomide in non-Hodgkin lymphoma. Galanina, N., Petrich, A., Nabhan, C.[2019]

Lenalidomide, especially when combined with rituximab (the 'R(2)' regimen), shows enhanced efficacy in treating indolent B-cell and mantle cell lymphomas, even in patients resistant to rituximab, while maintaining a manageable safety profile.

The most common serious side effect is asymptomatic neutropenia, which can be managed through dose adjustments, and while immune-related symptoms like rash are more frequent with the R(2) regimen, they are generally low-grade and manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas. Ruan, J., Shah, B., Martin, P., et al.[2020]

Lenalidomide is an FDA-approved immunomodulatory drug that shows strong efficacy in treating multiple myeloma and certain B-cell malignancies, particularly when combined with monoclonal antibodies like rituximab.

The drug works by modifying the tumor microenvironment and enhancing the activity of T and natural-killer (NK) cells, demonstrating excellent tolerability and potential to change treatment approaches for non-Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comprehensive review of lenalidomide in B-cell non-Hodgkin lymphoma. Arora, M., Gowda, S., Tuscano, J.[2022]

Lenalidomide, when used in combination with rituximab, has been shown to be an effective treatment for patients with relapsed or refractory follicular lymphoma, offering a chemotherapy-free option.

This combination therapy improves outcomes compared to using rituximab alone and may serve as a viable alternative to traditional chemoimmunotherapy for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in follicular lymphoma. Flowers, CR., Leonard, JP., Fowler, NH.[2021]

Isatuximab combined with carfilzomib and dexamethasone (Isa-Kd) demonstrated significantly better progression-free survival (PFS) compared to daratumumab combined with lenalidomide and dexamethasone (Dara-Rd) in patients with relapsed and/or refractory multiple myeloma, based on a matching-adjusted indirect comparison of 179 patients from the IKEMA trial and 286 patients from the POLLUX trial.

Patients receiving Isa-Kd experienced lower rates of treatment-emergent adverse events (TEAEs) compared to those on Dara-Rd, indicating a potentially safer profile for Isa-Kd in this treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect comparison of isatuximab plus carfilzomib and dexamethasone with daratumumab plus lenalidomide and dexamethasone in relapsed multiple myeloma. Richter, J., Lin, PL., Garcia-Horton, V., et al.[2023]

In the phase III AUGMENT trial, lenalidomide combined with rituximab significantly improved progression-free survival in patients with relapsed or refractory follicular lymphoma compared to placebo, showing particular benefit for elderly patients.

Lenalidomide has an acceptable safety profile, although it can cause more frequent cases of severe neutropenia, which can be managed with dosage adjustments and growth factor support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: A Review in Previously Treated Follicular Lymphoma. Blair, HA.[2021]

Lenalidomide is an effective oral immunomodulator approved for treating relapsed/refractory mantle cell lymphoma (MCL) after two prior therapies, showing significant activity in various B-cell non-Hodgkin lymphomas (NHL).

Combining lenalidomide with rituximab (R2) has demonstrated promising results in both first-line and relapsed/refractory settings, and ongoing trials are evaluating its use in combination with immunochemotherapy regimens like R-CHOP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comprehensive review of lenalidomide therapy for B-cell non-Hodgkin lymphoma. Witzig, TE., Nowakowski, GS., Habermann, TM., et al.[2020]

The combination treatment of elotuzumab, pomalidomide, and dexamethasone (EloPd) demonstrated a 55.4% overall response rate in a real-world study of 200 patients with relapsed/refractory multiple myeloma, aligning with results from the ELOQUENT-3 trial.

The safety profile of EloPd in this cohort was manageable and similar to that observed in clinical trials, indicating it is a viable treatment option for patients who have undergone at least two prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: a multicenter, retrospective real-world experience with 200 cases outside of controlled clinical trials. Gentile, M., Vigna, E., Palmieri, S., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02628405

R-ICE and Lenalidomide in Treating Patients With First ... This phase I/II trial studies the side effects and best dose of lenalidomide when given together with rituximab-ifosfamide-carboplatin-etoposide (R-ICE) and ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.TPS8073

Phase I/II study of R-ICE (rituximab-ifosfamide-carboplatin ... We developed phase I/II study to evaluate the safety and efficacy of the addition of Len (extended to 14 day schedule) to RICE (R2-ICE) for R/R-DLBCL patients.

3. mayo.edu mayo.edu/research/clinical-trials/cls-20214780

A Study of R-ICE and Lenalidomide for Treating Patients ... The purpose of this study is to assess the side effects and best dose of lenalidomide when given together with rituximab-ifosfamide-carboplatin-etoposide (R-ICE) ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4283736/

Addition of lenalidomide to rituximab, ifosfamide, ... However 10–15% of patients fail R-CHOP initially and 20–25% relapse, with 80% of the failures occurring within the first 18 months of treatment ...

5. withpower.com withpower.com/trial/r-ice-lenalidomide-for-refractory-large-b-cell-lymphoma-77d52

R-ICE + Lenalidomide for Refractory Large B-Cell Lymphoma This phase I/II trial studies the side effects and best dose of lenalidomide when given together with rituximab-ifosfamide-carboplatin-etoposide (R-ICE) and ...

6. clinicaltrial.be clinicaltrial.be/fr/details/10615?only_active=0&only_eligible=0&only_recruiting=0&per_page=100

R-ICE and Lenalidomide in Treating Patients With First-Re... To evaluate the effect of the addition of lenalidomide to RICE on the number (percentage) of patients proceeding to stem cell transplant (SCT).