Tafasitamab + Lenalidomide for Diffuse Large B-Cell Lymphoma

(frontMIND Trial)

Not currently recruiting at 453 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for diffuse large B-cell lymphoma (DLBCL), a type of blood cancer. Researchers are testing whether adding two drugs, tafasitamab (an antibody therapy) and lenalidomide (an immunomodulatory drug), to the standard chemotherapy regimen (R-CHOP) proves more effective than the standard treatment alone. Participants must have a DLBCL diagnosis, not have started treatment, and be considered high-risk. The goal is to determine if this new combination can improve outcomes for this specific cancer type. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that the combination of tafasitamab and lenalidomide is generally well-tolerated by patients with large B-cell lymphoma. In a study with 156 patients, 54% experienced at least one significant side effect. However, most participants managed the treatment over the long term. The final five-year analysis of the L-MIND study supports this, indicating that the combination can be used safely over extended periods.

While some patients might experience side effects, the treatment's safety is comparable to other therapies in this area. It is important to discuss any concerns with a healthcare provider to understand how these findings might relate to individual health. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lymphoma?

Researchers are excited about the combination of tafasitamab and lenalidomide for treating diffuse large B-cell lymphoma (DLBCL) because it offers a fresh approach compared to standard treatments like R-CHOP. Tafasitamab is a monoclonal antibody that targets CD19, a protein found on the surface of lymphoma cells, potentially leading to more direct and effective cancer cell destruction. Lenalidomide, on the other hand, enhances the immune system's ability to attack cancer cells. This combination could amplify the body's natural defenses against lymphoma, offering hope for improved outcomes in patients who may not respond well to existing therapies.

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

Research has shown that using tafasitamab and lenalidomide together may help treat large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL). In this trial, one group of participants will receive tafasitamab plus lenalidomide in addition to R-CHOP. Studies have found that this combination is generally well-tolerated by patients and can offer long-term benefits. Data from five years of analysis indicated significant improvements in patients. Specifically, a real-world study showed positive results for patients who received tafasitamab and lenalidomide, supporting its potential effectiveness for this condition. This treatment targets the CD19 protein on cancer cells, enabling the immune system to attack these cells more effectively. ^{1 2 4 6 7}

Who Is on the Research Team?

Incyte Medical Director

Principal Investigator

Incyte Corporation

Are You a Good Fit for This Trial?

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 had cancer before, but it wasn't related to blood.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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 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]

Citations

1. monjuvihcp.com monjuvihcp.com/dlbcl/long-term-analysis

5-year analysis: efficacy - Monjuvi The most common adverse reactions (≥20%) were neutropenia (51%), respiratory tract infection (51%), fatigue (38%), anemia (36%), diarrhea (36%), ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37646664/

final 5-year efficacy and safety findings in the phase II L-MIND ... This final 5-year analysis of L-MIND demonstrates that the immunotherapy combination of tafasitamab and lenalidomide is well tolerated and has long-term ...

3. ashpublications.org ashpublications.org/blood/article/142/26/2327/498041/Tafasitamab-and-lenalidomide-in-large-B-cell

Tafasitamab and lenalidomide in large B-cell lymphoma Tafasitamab and lenalidomide in large B-cell lymphoma: real-world outcomes in a multicenter retrospective study

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06299553

Study to Evaluate the Effectiveness of Tafasitamab in ... The PRO-MIND study is an Italian, multicenter, prospective observational cohort study to evaluate the effectiveness and the safety of tafasitamab in combination ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2666636725006426

561 Real-World Effectiveness of Tafasitamab (Tafa) for the ... We presented results from one such real-world study (RWS), but the limited median follow-up time of 6.5 months precluded robust evaluations of the clinical ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118608067

A Phase Ib, Open-Label, Randomized Study to Assess ... Treatment with tafasitamab/LEN achieved an ORR of 60%, a complete response (CR) rate of 42.5% and a median progression-free survival (PFS) of 12.1 months.

7. haematologica.org haematologica.org/article/view/haematol.2020.275958

Long-term outcomes from the Phase II L-MIND study of ... To further determine the long-term clinical efficacy and safety of tafasitamab plus lenalidomide treatment in patients with R/R DLBCL, we provide updated data ...