Tafasitamab + Lenalidomide + Rituximab for Follicular & Marginal Zone Lymphoma

(InMIND Trial)

Recruiting at 318 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

654 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if adding two drugs, tafasitamab and lenalidomide, to an existing treatment (rituximab) is more effective than just adding one drug (lenalidomide) for patients with certain types of lymphoma that have returned or not responded to treatment. The drugs aim to better target and destroy cancer cells while boosting the body's immune response against the cancer. Lenalidomide has shown activity in various lymphoma subtypes, including diffuse large B-cell lymphoma, and is often combined with rituximab for enhanced efficacy.

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.

What data supports the effectiveness of the drug combination of Lenalidomide and Rituximab for treating follicular lymphoma?

Research shows that Lenalidomide combined with Rituximab significantly improves progression-free survival in patients with relapsed or refractory follicular lymphoma compared to placebo plus Rituximab. This combination has been effective even in patients whose disease did not respond to Rituximab alone. ^{1 2 3 4 5}

Is the combination of Tafasitamab, Lenalidomide, and Rituximab safe for humans?

The combination of Lenalidomide and Rituximab, known as the R(2) regimen, has a manageable safety profile in treating certain types of lymphoma. Common side effects include neutropenia (low white blood cell count) and mild skin reactions, which are generally manageable with dose adjustments. Lenalidomide has also been associated with rare side effects like thrombosis (blood clots) and abdominal pain. ^{2 6 7 8 9}

What makes the drug combination of Tafasitamab, Lenalidomide, and Rituximab unique for treating follicular and marginal zone lymphoma?

This drug combination is unique because it includes Tafasitamab, a monoclonal antibody that targets CD19 on B-cells, potentially enhancing the immune response against cancer cells. When combined with Lenalidomide and Rituximab, it offers a novel approach that may improve outcomes for patients with follicular and marginal zone lymphoma, especially those who have relapsed or are refractory to other treatments. ^{2 3 10 11 12}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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]

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, 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]

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]

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]

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]

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]

References

1. 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]

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

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

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

Lenalidomide in follicular lymphoma. [2021]

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

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

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

Combination of Lenalidomide and Rituximab Overcomes Rituximab Resistance in Patients with Indolent B-cell and Mantle Cell Lymphomas. [2022]

6. 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]

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

Results of a phase II study of lenalidomide and rituximab for refractory/relapsed chronic lymphocytic leukemia. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Lenalidomide-induced arthritis: A case report and review of literature and pharmacovigilance databases. [2022]

9. United States 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. [2021]

10. England 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. [2020]

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

Tafasitamab: First Approval. [2022]

12. Germany 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. [2023]