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

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

30 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination R-ICE + Lenalidomide for Refractory Large B-Cell Lymphoma?

Research shows that lenalidomide, when combined with rituximab, has been effective in treating various types of B-cell lymphomas, including diffuse large B-cell lymphoma, by prolonging progression-free survival and demonstrating significant anti-tumor effects. ^{1 2 3 4 5}

Is the combination of R-ICE and Lenalidomide safe for treating refractory large B-cell lymphoma?

Lenalidomide, when used alone or with rituximab, has a manageable safety profile in B-cell lymphomas, with common side effects like neutropenia (low white blood cell count) and fatigue, which are generally manageable with dose adjustments. Immune-related symptoms such as rash and tumor flare may occur, but severe reactions are rare. Venous thromboembolism (blood clots) is uncommon, but preventive measures are recommended. ^{1 6 7 8 9}

What makes the R-ICE + Lenalidomide drug unique for treating refractory large B-cell lymphoma?

The R-ICE + Lenalidomide drug is unique because it combines lenalidomide, an immunomodulatory drug that enhances the immune system's ability to fight cancer, with a chemotherapy regimen (R-ICE) that includes rituximab, carboplatin, etoposide, and ifosfamide. This combination leverages lenalidomide's ability to alter the tumor environment and boost immune cell activity, potentially improving outcomes in patients with refractory large B-cell lymphoma. ^{1 2 4 10 11}

What is the purpose of this trial?

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 to see how well they work in treating patients with diffuse large B-cell lymphoma that has returned after a period of improvement (relapsed) and that has not responded to previous treatment (refractory). Drugs used in chemotherapy, such as rituximab, ifosfamide, carboplatin, etoposide, and lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving lenalidomide with R-ICE may be a better treatment for patients with diffuse large B-cell lymphoma.

Research Team

Grzegorz S Nowakowski

Principal Investigator

Academic and Community Cancer Research United

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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, 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]

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]

References

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

The evolving role of lenalidomide in non-Hodgkin lymphoma. [2019]

2. New Zealand pubmed.ncbi.nlm.nih.gov

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

3. New Zealand pubmed.ncbi.nlm.nih.gov

Real-World, Single-Center Data for Lenalidomide Plus Rituximab in Relapsed or Refractory Diffuse Large B-Cell Lymphoma and Transformed Follicular Lymphoma. [2022]

4. England pubmed.ncbi.nlm.nih.gov

A comprehensive review of lenalidomide in B-cell non-Hodgkin lymphoma. [2022]

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

Phase 1b dose-finding study of rituximab, lenalidomide, and ibrutinib (R2I) in patients with relapsed/refractory mantle cell lymphoma. [2023]

6. Italy 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. [2023]

7. England pubmed.ncbi.nlm.nih.gov

A real-world efficacy and safety analysis of combined carfilzomib, lenalidomide, and dexamethasone (KRd) in relapsed/refractory multiple myeloma. [2021]

8. United States 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. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas. [2020]

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

Lenalidomide in follicular lymphoma. [2021]

11. England pubmed.ncbi.nlm.nih.gov

A comprehensive review of lenalidomide therapy for B-cell non-Hodgkin lymphoma. [2020]