Tafasitamab + Lenalidomide + Rituximab for Follicular and Marginal Zone Lymphomas

Overseen By Sanjal Desai, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Masonic Cancer Center, University of Minnesota

Must not be taking: Antivirals

Disqualifiers: Hepatitis, HIV, CNS involvement, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 1

Duration: 6 months

65 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of drugs—tafasitamab, lenalidomide, and rituximab—to evaluate their safety and effectiveness for two specific types of non-Hodgkin lymphoma: follicular and marginal zone. Researchers aim to determine whether adding tafasitamab to the other two treatments can improve outcomes for those who have not yet received treatment for their lymphoma. Suitable candidates for this trial have either follicular or marginal zone lymphoma, have not undergone any treatment, and require intervention due to symptoms like night sweats or weight loss. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you must not have had prior systemic therapy for lymphoma and should be able to tolerate certain preventive treatments while on lenalidomide.

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

Studies have shown that the combination of tafasitamab, lenalidomide, and rituximab is generally safe. While some side effects might occur, doctors can usually manage them. Research indicates that common side effects include fatigue, diarrhea, and a drop in white blood cells, which can hinder the body's ability to fight infections.

In a study on this drug combination, the safety results aligned with expectations from earlier research. This suggests that, although side effects can occur, they are usually not severe and can be managed with proper medical care.

For those considering joining a trial like this, discussing expectations and side effect management with the medical team is important. ^{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 follicular and marginal zone lymphomas because it offers a unique approach compared to standard options. Most existing treatments for these conditions involve chemotherapy and monoclonal antibodies like rituximab alone. However, tafasitamab is a novel monoclonal antibody that targets CD19, a protein on the surface of B-cells, and works alongside lenalidomide, an immune-modulating drug, to enhance the body's immune response against cancer cells. This combination aims to improve the effectiveness of treatment by boosting the immune system while directly targeting cancer cells, which could lead to better outcomes for patients.

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

This trial will evaluate the combination of tafasitamab, lenalidomide, and rituximab for treating both follicular lymphoma (FL) and marginal zone lymphoma (MZ). Research has shown that this combination is promising for FL, as studies demonstrated that patients taking these drugs together experienced about 22.4 months before disease progression, compared to 13.9 months with other treatments, indicating a significant benefit. For MZ, while specific data is limited, the success in similar conditions like FL offers hope for its effectiveness. Overall, the combination has proven to be safe and manageable, making it a hopeful treatment option for participants in this trial. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adults with two types of untreated lymphoma: follicular and marginal zone. They must have a large tumor or multiple affected sites, symptoms like fever, night sweats, or significant weight loss. People who've had previous systemic therapy for lymphoma can't participate.

Inclusion Criteria

My diagnosis is marginal zone lymphoma confirmed by tissue analysis.

My lymphoma is CD20+ follicular, stages 1, 2, or 3a.

I have not had any drug treatments for lymphoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tafasitamab, rituximab, and lenalidomide over 6 cycles, with adjustments based on response

6 months

Weekly visits during Cycle 1, bi-weekly visits during Cycles 2-3, monthly visits during Cycles 4-6

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Lenalidomide
• Rituximab
• Tafasitamab

Trial Overview The trial tests Tafasitamab combined with Lenalidomide and Rituximab in patients who haven't been treated before for their lymphoma. It's a phase II study that looks at safety and effectiveness separately in two groups: one with follicular lymphoma (FL) and another with marginal zone lymphoma (MZL).

How Is the Trial Designed?

Group I: Marginal Zone Lymphoma Experimental Treatment 3 Interventions

On Cycle 1, patients will receive an infusion of tafasitamab 12 mg/kg IV on Day 1, Day 8, Day 15 and day 22, rituximab 375 mg/m2 IV on Day 1, Day 8, Day 15 and Day 22, and lenalidomide 20 mg PO Day 1 through Day 21. On Cycles 2-3, patients will receive tafasitamab 12 mg/kg IV on Day 1, Day 8, Day 15 and day 22, rituximab 375 mg/m2 IV on day 1, and lenalidomide 20 mg PO Day 1-21. On Cycles 4-6, patients will receive an infusion of tafasitamab 12 mg/kg IV on Day 1, Rituximab 375 mg/m2 IV on Day 1, and lenalidomide 20 mg PO from Day 1-21. At the end of Cycle 6, patients on both cohorts will be assessed by Lugano standard. Patients in complete remission (CR) will continue on tafasitamab/rituximab and discontinue lenalidomide. Patients with partial response (PR) or stable disease (SD) will continue on all three drugs, tafasitamab/rituximab/lenalidomide, and if progressive disease (PD) will discontinue study.

Group II: Follicular Lymphoma Experimental Treatment 3 Interventions

On Cycle 1, patients will receive an infusion of tafasitamab 12 mg/kg IV on Day 1, Day 8, Day 15 and day 22, rituximab 375 mg/m2 IV on Day 1, Day 8, Day 15 and Day 22, and lenalidomide 20 mg PO Day 1 through Day 21. On Cycles 2-3, patients will receive tafasitamab 12 mg/kg IV on Day 1, Day 8, Day 15 and day 22, rituximab 375 mg/m2 IV on day 1, and lenalidomide 20 mg PO Day 1-21. On Cycles 4-6, patients will receive an infusion of tafasitamab 12 mg/kg IV on Day 1, Rituximab 375 mg/m2 IV on Day 1, and lenalidomide 20 mg PO from Day 1-21. At the end of Cycle 6, patients on both cohorts will be assessed by Lugano standard. Patients in complete remission (CR) will continue on tafasitamab/rituximab and discontinue lenalidomide. Patients with partial response (PR) or stable disease (SD) will continue on all three drugs, tafasitamab/rituximab/lenalidomide, and if progressive disease (PD) will discontinue study.

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

Incyte Corporation

Industry 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

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41090546

The emerging role of tafasitamab in follicular lymphoma Clinical trial data support its efficacy and manageable safety profile in FL starting from fisrt relapse, including in high-risk FL subgroups ...

2. incytemi.com incytemi.com/document/Poster/ICML%202025%20-%20inMIND%20Study%20(oral%20presentation).pdf

Outcomes From the Phase 3 inMIND Study of Tafasitamab ... *Death for 1 patient was reported but not recorded in the end-of-study form. One patient randomized to the placebo + len + R group is ...

3. ascopost.com ascopost.com/news/june-2025/tafasitamab-plus-lenalidomide-and-rituximab-significantly-improves-outcomes-in-relapsedrefractory-follicular-lymphoma/

Tafasitamab Plus Lenalidomide and Rituximab ... The median progression-free survival was substantially improved at 22.4 months for patients receiving tafasitamab vs 13.9 months in the placebo ...

4. 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 ...

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

LBA-1 Tafasitamab Plus Lenalidomide and Rituximab for ... Conclusions: Addition of tafa to len+R resulted in significant and clinically meaningful improvement in PFS, representing a 57% reduction in ...