Tafasitamab + Lenalidomide for Diffuse Large B-Cell Lymphoma

(frontMIND Trial)

Recruiting at 407 trial locations

Overseen By Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Incyte Corporation

Must not be taking: Anthracyclines

Disqualifiers: Other lymphoma types, CNS involvement, 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: 3

Duration: 18 weeks

899 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment combining an antibody, an immune-boosting drug, and standard chemotherapy for high-risk patients with newly diagnosed aggressive lymphoma. The goal is to see if this combination works better than standard chemotherapy alone. Rituximab, when combined with standard chemotherapy, has shown significant improvements in response rates and survival for patients with aggressive lymphoma.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug combination Tafasitamab and Lenalidomide for treating diffuse large B-cell lymphoma?

Research shows that the combination of Tafasitamab and Lenalidomide improves survival outcomes in patients with relapsed or refractory diffuse large B-cell lymphoma, with a significant overall survival benefit compared to other treatments like polatuzumab vedotin/bendamustine/rituximab and rituximab/lenalidomide. Additionally, a study found that 57.5% of patients responded to the treatment, with 41.3% achieving complete response, indicating long-term clinical benefits. ^{1 2 3 4 5}

Is the combination of Tafasitamab and Lenalidomide safe for treating diffuse large B-cell lymphoma?

The combination of Tafasitamab and Lenalidomide has been shown to be generally safe for treating diffuse large B-cell lymphoma, with manageable side effects. In studies, common side effects included blood-related issues like neutropenia (low white blood cell count), and some patients experienced moderate non-blood-related side effects. Long-term studies have confirmed that this treatment is well-tolerated with no new safety concerns. ^{3 6 7 8 9}

What makes the drug combination of Tafasitamab and Lenalidomide unique for treating diffuse large B-cell lymphoma?

The combination of Tafasitamab and Lenalidomide is unique because it is the first therapy approved as a second-line treatment for patients with relapsed or refractory diffuse large B-cell lymphoma who are not eligible for stem cell transplantation. Tafasitamab is an anti-CD19 immunotherapy that works synergistically with Lenalidomide, showing long-term clinical benefits and durable responses in patients. ^{1 3 5 8 9}

Research Team

Incyte Medical Director

Principal Investigator

Incyte Corporation

Eligibility Criteria

This trial is for adults with untreated CD20-positive DLBCL, a type of lymphoma. They must be suitable for R-CHOP therapy and have an ECOG performance status of 0-2, meaning they are fully active or at least ambulatory. Participants need proper heart function and agree to contraception if applicable. Those with certain other cancers, CNS involvement by lymphoma, significant health issues, infections like TB, or prior anti-lymphoma treatment aren't eligible.

Inclusion Criteria

I am considered a suitable candidate for R-CHOP treatment.

Diagnosis to treatment interval ≤ 28 days

I can take care of myself and perform daily activities.

Exclusion Criteria

My lymphoma type is not specifically listed.

My cancer has spread to my brain.

I have received treatments for lymphoma before the start of this clinical trial.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tafasitamab plus lenalidomide in addition to R-CHOP or placebo for six 21-day cycles

18 weeks

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

Up to 62 months

Treatment Details

Interventions

• Cyclophosphamide
• Lenalidomide
• Prednisone
• Rituximab
• Tafasitamab
• Vincristine

Trial Overview The study tests the effectiveness and safety of adding tafasitamab plus lenalidomide to the standard R-CHOP regimen against R-CHOP alone in high-risk DLBCL patients. It's a phase 3 trial where participants are randomly assigned to either receive the new combination or placebo alongside their regular chemotherapy.

Participant Groups

Group I: Tafasitamab plus lenalidomide in addition to R-CHOP Experimental Treatment 7 Interventions

Patients will receive tafasitamab plus lenalidomide in addition to R-CHOP for six 21-day cycles: Tafasitamab dose: 12 mg/kg body weight. Each 21-day cycle (cycles 1-6) will comprise of a tafasitamab IV infusion on Day 1, Day 8 and Day 15. Lenalidomide dose: 25 mg as a starting dose per os (orally) once per day on Days 1-10 of each 21-day cycle R-CHOP dose: Rituximab (or locally approved biosimilar) 375 mg/m2, IV Day 1 of every 21-day cycle; Cyclophosphamide 750 mg/m2, IV Day 1 of 21-day cycle; Doxorubicin 50 mg/m2, IV Day 1 of 21-day cycle; Vincristine 1.4 mg/m2 (max 2 mg) IV Day 1 of 21-day cycle; Prednisone/prednisolone 100 mg/day, per os, Day 1-5 of every 21-day cycle

Group II: Tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP Placebo Group 7 Interventions

Patients will receive tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP for six 21-day cycles: Tafasitamab placebo: 0.9% saline solution Days 1, 8 and 15 of each 21-day cycle Lenalidomide placebo: Days 1-10 of each 21-day cycle R-CHOP dose: Rituximab (or locally approved biosimilar) 375 mg/m2, IV Day 1 of every 21-day cycle; Cyclophosphamide 750 mg/m2, IV Day 1 of 21-day cycle; Doxorubicin 50 mg/m2, IV Day 1 of 21-day cycle; Vincristine 1.4 mg/m2 (max 2 mg) IV Day 1 of 21-day cycle; Prednisone/prednisolone 100 mg/day, per os, Day 1-5 of every 21-day cycle

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

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• 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

MorphoSys AG

Lead Sponsor

Trials

27

Recruited

6,600+

Findings from Research

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]

In the final 5-year analysis of the L-MIND study involving 80 patients with relapsed/refractory diffuse large B-cell lymphoma, the combination of tafasitamab and lenalidomide showed a significant objective response rate of 57.5%, with a complete response rate of 41.3%.

The treatment demonstrated long-term clinical benefits, with a median overall survival of 33.5 months and manageable adverse events, indicating that this immunotherapy combination is both effective and well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tafasitamab for patients with relapsed or refractory diffuse large B-cell lymphoma: final 5-year efficacy and safety in the phase II L-MIND study. Duell, J., Abrisqueta, P., Andre, M., et al.[2023]

In the RE-MIND2 study, patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) treated with tafasitamab plus lenalidomide showed significantly prolonged overall survival compared to those receiving standard systemic therapies, with a hazard ratio of 0.55.

When specifically compared to bendamustine plus rituximab and rituximab plus gemcitabine/oxaliplatin, tafasitamab plus lenalidomide demonstrated even greater survival benefits, with hazard ratios of 0.42 and 0.47, respectively, indicating its potential as a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Efficacy of Tafasitamab plus Lenalidomide versus Systemic Therapies for Relapsed/Refractory DLBCL: RE-MIND2, an Observational Retrospective Matched Cohort Study. Nowakowski, GS., Yoon, DH., Peters, A., et al.[2023]

In a phase I study involving 21 elderly patients with untreated diffuse large B-cell lymphoma, the combination of lenalidomide and standard chemotherapy resulted in a high overall response rate of 90%, with 81% achieving complete remission.

The maximum tolerated dose of lenalidomide was determined to be 15 mg/day, with manageable safety concerns, including hematologic toxicities like neutropenia in 28% of treatment courses, indicating that this regimen is safe for elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated, elderly patients with diffuse large B-cell lymphoma: a phase I study by the Fondazione Italiana Linfomi. Chiappella, A., Tucci, A., Castellino, A., et al.[2021]

Lenalidomide, a derivative of thalidomide, has improved potency and a better side-effect profile, particularly with reduced neurologic toxicity compared to its predecessor.

While lenalidomide shows promise in treating conditions like myelodysplastic syndrome and multiple myeloma, there are still concerns about pro-thrombotic effects, especially when used with dexamethasone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: an immunomodulatory drug. Crane, E., List, A.[2018]

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 the phase II L-MIND study, tafasitamab combined with lenalidomide showed a 57.5% objective response rate in patients with relapsed/refractory diffuse large B-cell lymphoma, with a complete response in 40% of patients after more than 35 months of follow-up.

The treatment demonstrated a median overall survival of 33.5 months and a median duration of response of 43.9 months, with no unexpected toxicities, indicating a favorable safety and efficacy profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma. Duell, J., Maddocks, KJ., González-Barca, E., et al.[2021]

References

1. 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]

2. 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]

3. Italy pubmed.ncbi.nlm.nih.gov

Tafasitamab for patients with relapsed or refractory diffuse large B-cell lymphoma: final 5-year efficacy and safety in the phase II L-MIND study. [2023]

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

Improved Efficacy of Tafasitamab plus Lenalidomide versus Systemic Therapies for Relapsed/Refractory DLBCL: RE-MIND2, an Observational Retrospective Matched Cohort Study. [2023]

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

Broadening the MIND: Tafasitamab and Lenalidomide versus Synthetic Controls. [2023]

6. Italy pubmed.ncbi.nlm.nih.gov

Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated, elderly patients with diffuse large B-cell lymphoma: a phase I study by the Fondazione Italiana Linfomi. [2021]

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

Lenalidomide: an immunomodulatory drug. [2018]

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

Tafasitamab: First Approval. [2022]

9. Italy pubmed.ncbi.nlm.nih.gov

Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma. [2021]