Tafasitamab + Lenalidomide + Rituximab for Follicular & Marginal Zone Lymphoma

(InMIND Trial)

Not currently recruiting at 371 trial locations

Overseen By Incyte Corporation Call Center (ex-US)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Incyte Corporation

Must be taking: Rituximab

Must not be taking: Lenalidomide, others

Disqualifiers: Pregnancy, Non-hematologic malignancy, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: up to 34 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding tafasitamab (an antibody therapy) to lenalidomide and rituximab benefits patients more than lenalidomide and rituximab alone. The focus is on treating follicular lymphoma or marginal zone lymphoma that has returned or not responded to previous treatments. Suitable candidates have experienced a recurrence or resistance after at least one prior therapy. As a Phase 3 trial, this study represents the final step before FDA approval, giving participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had any systemic anti-lymphoma or investigational therapy within 28 days before starting the trial.

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

Research has shown that the combination of tafasitamab, lenalidomide, and rituximab is generally safe for patients. Studies have found this treatment to be well-tolerated overall. Most side effects were expected, including tiredness, low white blood cell counts, and diarrhea. Importantly, the FDA has already approved this combination for treating certain types of lymphoma, highlighting its established safety. For specific concerns about side effects, consulting a healthcare provider can be helpful. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Tafasitamab, Lenalidomide, and Rituximab for treating relapsed or refractory follicular and marginal zone lymphoma because it introduces a novel approach. Unlike many standard treatments that often rely on chemotherapy, this combination includes Tafasitamab, a monoclonal antibody specifically designed to enhance the immune system's ability to target and destroy cancer cells. Lenalidomide also contributes by modulating the immune response and directly attacking cancer cells. This treatment could potentially offer a more targeted and effective option with fewer side effects compared to traditional chemotherapy.

What evidence suggests that this trial's treatments could be effective for follicular and marginal zone lymphoma?

Research has shown that a combination of three drugs—tafasitamab, lenalidomide, and rituximab—holds promise for treating relapsed or refractory follicular lymphoma, a type of blood cancer. This combination aids the immune system in identifying and destroying cancer cells. In this trial, some participants will receive this combination. Studies have found this treatment effective, leading to its FDA approval for this cancer type. Specifically, patients in clinical trials who received this combination improved more than those who did not. This suggests that adding tafasitamab to the usual treatment with lenalidomide and rituximab can lead to better outcomes for patients with this condition. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for adults with relapsed/refractory Follicular Lymphoma or Marginal Zone Lymphoma who've had prior anti-CD20 immunotherapy or chemo-immunotherapy. Participants must be able to take blood clot prevention meds, not be pregnant or breastfeeding, and have no major heart issues, active infections, HIV/HCV/HBV, CNS lymphoma involvement, or recent other lymphoma treatments.

Inclusion Criteria

My lymphoma is confirmed to be of a specific type and grade.

I am willing to take medication to prevent blood clots as advised.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I have been treated with lenalidomide and rituximab together.

I am currently fighting an infection in my body.

I have been diagnosed with congestive heart failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tafasitamab and lenalidomide as an add-on to rituximab or placebo plus lenalidomide and rituximab

up to 34 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Lenalidomide
• Placebo
• Rituximab
• Tafasitamab

Trial Overview The study tests if adding Tafasitamab to the combination of Lenalidomide and Rituximab improves outcomes for patients compared to a placebo plus Lenalidomide and Rituximab. It's a Phase 3 trial where participants are randomly assigned to either the drug group or placebo group without knowing which one they're in.

How Is the Trial Designed?

Group I: Arm A : tafasitamab + rituximab + lenalidomide Experimental Treatment 3 Interventions

Adult patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) Grade 1 to 3a or R/R Marginal Zone Lymphoma (MZL)

Group II: Arm B : placebo+rituximab+lenalidomide Placebo Group 3 Interventions

Adult patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) Grade 1 to 3a or R/R Marginal Zone Lymphoma (MZL)

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?

Incyte Corporation

Lead Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Published Research Related to This Trial

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, 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]

The combination of rituximab and lenalidomide (R2) significantly improves treatment efficacy for recurrent non-Hodgkin lymphoma compared to rituximab alone, leading to its approval for use in previously treated patients with follicular and marginal zone lymphoma.

R2 has a manageable safety profile, with common adverse events including grade 3/4 neutropenia, skin rashes, and gastrointestinal issues, indicating that while it is effective, careful monitoring and management of side effects are necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Adverse Events From the Combination of Rituximab and Lenalidomide in the Treatment of Patients With Follicular and Low-Grade Non-Hodgkin Lymphoma. Cheson, BD., Morschhauser, F., Martin, P.[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]

Lenalidomide, while effective as a maintenance treatment for mantle-cell lymphoma, can induce rare adverse events such as arthritis, as demonstrated in a case study of a 71-year-old patient who developed scapular-belt arthritis after treatment.

Pharmacovigilance data revealed that arthritis is a rare side effect of lenalidomide, with only three reported cases in France and accounting for just 0.13% of adverse events in the international VigiBase® database, highlighting the need for awareness among healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide-induced arthritis: A case report and review of literature and pharmacovigilance databases. Icard, C., Mocquot, P., Nogaro, JC., 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]

In a phase II trial involving 50 patients with indolent B-cell or mantle cell lymphomas who were previously resistant to rituximab, the combination of lenalidomide and rituximab resulted in a significant increase in overall response rate from 30.2% after lenalidomide alone to 62.8% after adding rituximab.

The median progression-free survival for patients receiving the lenalidomide-rituximab combination was 22.2 months, which was significantly longer than the 9.13 months observed with prior rituximab treatment, indicating that this combination can effectively overcome previous resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of Lenalidomide and Rituximab Overcomes Rituximab Resistance in Patients with Indolent B-cell and Mantle Cell Lymphomas. Chong, EA., Ahmadi, T., Aqui, NA., et al.[2022]

In a phase 2 study involving 81 patients with relapsed or refractory diffuse large B-cell lymphoma, the combination of tafasitamab and lenalidomide resulted in a 60% objective response rate, with 43% achieving a complete response, indicating significant antitumor activity.

The treatment was generally well tolerated, although serious adverse events occurred in 51% of patients, with neutropenia being the most common, suggesting that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Salles, G., Duell, J., González Barca, E., et al.[2020]

In a study comparing tafasitamab+lenalidomide to other treatments for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), significant overall survival benefits were observed against polatuzumab vedotin+bendamustine+rituximab and rituximab+lenalidomide, indicating tafasitamab+lenalidomide may be a more effective option.

When compared to CAR-T therapies, tafasitamab+lenalidomide showed comparable overall survival outcomes, suggesting it could be a viable alternative for patients who are ineligible for autologous stem cell transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RE-MIND2: comparative effectiveness of tafasitamab plus lenalidomide versus polatuzumab vedotin/bendamustine/rituximab (pola-BR), CAR-T therapies, and lenalidomide/rituximab (R2) based on real-world data in patients with relapsed/refractory diffuse large B-cell lymphoma. Nowakowski, GS., Yoon, DH., Mondello, P., 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]

Tafasitamab, an anti-CD19 monoclonal antibody, received accelerated approval in July 2020 for treating adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in combination with lenalidomide, marking it as the first second-line therapy approved for this patient group in the USA.

The drug is administered intravenously at a recommended dose of 12 mg per kg and is also being explored for use in other B-cell malignancies, indicating its potential versatility in treating various types of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tafasitamab: First Approval. Hoy, SM.[2022]

Citations

1. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-tafasitamab-cxix-relapsed-or-refractory-follicular-lymphoma

FDA approves tafasitamab-cxix for relapsed or refractory ... The recommended tafasitamab-cxix dose is 12 mg/kg as an intravenous infusion for a maximum of 12 cycles with lenalidomide and rituximab.

2. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incyte-announces-fda-approval-monjuvir-tafasitamab-cxix

Incyte Announces FDA Approval of Monjuvi® (tafasitamab- ... Monjuvi (tafasitamab-cxix) in combination with rituximab and lenalidomide is the first FDA-approved CD19- and CD20-targeted immunotherapy combination for adult ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04680052

NCT04680052 | A Phase 3 Study to Assess Efficacy and ... This is a Phase 3 double-blind, placebo-controlled, randomized study designed to investigate whether tafasitamab and lenalidomide as an add-on to rituximab ...

4. onclive.com onclive.com/view/fda-approves-tafasitamab-plus-lenalidomide-and-rituximab-for-r-r-follicular-lymphoma

FDA Approves Tafasitamab Plus Lenalidomide and ... The FDA approved tafasitamab-cxix plus lenalidomide and rituximab for adult patients with relapsed or refractory follicular lymphoma.

5. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper212970.html

LBA-1 Tafasitamab Plus Lenalidomide and Rituximab for ... Median number of prior lines of tx was 1 (range, 1-10), 45% had ≥2 prior lines, 32% had disease progression within 24 m (POD24), and 43% were ...

6. monjuvihcp.com monjuvihcp.com/fl/

MONJUVI® (tafasitamab-cxix): Treatment for R/R FL MONJUVI® (tafasitamab-cxix), in combination with rituximab and lenalidomide, can be used to treat R/R follicular lymphoma through targeted immunotherapy.