Tafasitamab + Lenalidomide for CNS Lymphoma

Overseen By Hayley Wallace

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: James Rubenstein

Must not be taking: Anti-CD19 therapy

Disqualifiers: HIV, CNS PTLD, uncontrolled infection, others

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

Compensation: Varies

Number of Visits: Unknown

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, Lenalidomide (Revlimid) and Tafasitamab (Monjuvi or Minjuvi), to determine their effectiveness for individuals whose brain cancer, specifically central nervous system lymphoma, has returned. Researchers believe Tafasitamab might facilitate medicine crossing into the brain more easily, which could significantly impact future treatments. Individuals with recurrent central nervous system lymphoma, particularly affecting the brain or eyes, might be suitable candidates. As a Phase 1, Phase 2 trial, this study aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

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 received systemic anti-cancer therapies within 2 weeks, radiation within 1 week, or antibody therapy within 4 weeks before starting the trial. It's best to discuss your specific medications with the trial team.

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 has been tested in patients with large B-cell lymphoma. In these studies, most patients tolerated the treatment well, although some experienced side effects. Common side effects included low blood cell counts, tiredness, and nausea. More serious side effects occurred but were less common.

For central nervous system (CNS) lymphoma, this combination remains under investigation. As this is an early-stage trial, the safety for CNS lymphoma is not yet fully known. However, the testing of Tafasitamab and Lenalidomide suggests they have demonstrated sufficient safety in earlier research to warrant further study.

Prospective trial participants should discuss potential risks and benefits with the trial team. They can provide more detailed information about what to expect. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for CNS lymphoma?

Most treatments for CNS lymphoma involve chemotherapy and radiation, which can have significant side effects and varying effectiveness. Unlike these standard options, Tafasitamab and Lenalidomide offer a targeted approach that could enhance treatment effectiveness. Tafasitamab is an antibody that specifically targets the CD19 protein on lymphoma cells, potentially allowing for more precise destruction of cancerous cells. Meanwhile, Lenalidomide modulates the immune system, potentially enhancing the body’s natural ability to fight off cancer. Researchers are excited about this combination because it represents a more focused and potentially less toxic approach to treating CNS lymphoma.

What evidence suggests that this treatment might be an effective treatment for CNS lymphoma?

Research has shown that combining Tafasitamab with Lenalidomide may help treat central nervous system (CNS) lymphoma. Tafasitamab, an antibody targeting the CD19 protein on cancer cells, might enhance Lenalidomide's effectiveness. In past studies with large B-cell lymphoma, this combination proved effective, though results varied. Some patients experienced significant improvement, while others saw less benefit. Early findings suggest that Tafasitamab might also help other drugs reach the brain more easily, which is crucial for treating CNS conditions. This approach remains under investigation in this trial, so results may change as further research is conducted. ^{1 2 3 4 6}

Who Is on the Research Team?

James Rubenstein, MD, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

Adults with relapsed B-cell CNS lymphoma, including those who've had stem cell transplants but not recent anti-cancer treatments or certain other therapies. Must have good organ function and no serious medical issues that could affect safety. Women of childbearing age must agree to pregnancy testing and use contraception.

Inclusion Criteria

I have another cancer, but it won't affect this trial's treatment.

I had hepatitis C but am cured, or I'm being treated with no detectable virus.

I have CNS lymphoma in the brain and have undergone at least one treatment.

Exclusion Criteria

I am not pregnant or breastfeeding, and if of child-bearing potential, I am using effective birth control.

I have never received anti-CD19 or CAR-T therapy.

I haven't had cancer treatments like chemotherapy, radiation, or antibody therapy in the specified time before starting this trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Participants receive Tafasitamab and Lenalidomide to determine the maximum tolerated dose and recommended phase 2 dose

Up to 1 cycle (28 days)

Multiple visits for dosing and monitoring

Phase 2 Treatment

Participants receive Tafasitamab and Lenalidomide at the recommended phase 2 dose to evaluate clinical benefit

Up to 3 months

Multiple visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Lenalidomide
• Tafasitamab

Trial Overview The trial is exploring the effectiveness of Tafasitamab combined with Lenalidomide in patients with relapsed CNS lymphoma. It's an open-label study, meaning everyone knows what treatment they're getting, focusing on how well this combination crosses the blood-brain barrier.

How Is the Trial Designed?

Group I: Phase 2 (Tafasitamab, Lenalidomide) Experimental Treatment 2 Interventions

Participants will be given 12mg of Tafasitamab on days 1, 4, 8, 15, and 22 of cycle 1, days 1, 8, 15, and 22 of cycles 2 \& 3, and days 1 and 15 for any cycle thereafter. Participants will also be given daily Lenalidomide on days 1-21 of each cycle at the recommended phase 2 dose.

Group II: Phase 1 (Tafasitamab, Lenalidomide) Experimental Treatment 2 Interventions

Participants will be given 12mg of Tafasitamab on days 1, 4, 8, 15, and 22 of cycle 1, days 1, 8, 15, and 22 of cycles 2 \& 3, and days 1 and 15 for any cycle thereafter. Participants will also be given daily Lenalidomide on days 1-21 of each cycle.

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?

James Rubenstein

Lead Sponsor

Trials

3

Recruited

70+

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

Published Research Related to This Trial

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 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 study comparing tafasitamab combined with lenalidomide to lenalidomide alone in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), the combination therapy showed a significantly higher overall response rate of 67.1% compared to 34.2% for lenalidomide monotherapy.

The combination therapy also resulted in a higher complete response rate of 39.5% versus 13.2% for lenalidomide alone, indicating that tafasitamab enhances the efficacy of lenalidomide in treating this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RE-MIND: Comparing Tafasitamab + Lenalidomide (L-MIND) with a Real-world Lenalidomide Monotherapy Cohort in Relapsed or Refractory Diffuse Large B-cell Lymphoma. Zinzani, PL., Rodgers, T., Marino, D., et al.[2023]

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]

Tafasitamab plus lenalidomide (TAFA + LEN) showed significantly better overall survival (OS) and progression-free survival (PFS) compared to standard treatments like polatuzumab vedotin + bendamustine + rituximab (POLA + BR) and bendamustine + rituximab (BR) in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).

The study found that TAFA + LEN was associated with longer duration of response (DOR) and higher complete response rates (CRR), indicating its potential as a more effective treatment option, although further validation through large randomized trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tafasitamab Plus Lenalidomide Versus 3 Rituximab-Based Treatments for Non-Transplant Eligible Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Matching-Adjusted Indirect Comparison. Cordoba, R., Prawitz, T., Westley, T., et al.[2022]

Tafasitamab, a monoclonal antibody targeting CD19, showed a significant objective response rate of 56.8% in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) during the L-MIND clinical trial, with a median duration of response of 34.6 months.

The treatment was associated with notable adverse events, particularly infections (72.8% of patients) and blood disorders (65.4%), indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Tafasitamab in Combination With Lenalidomide for the Treatment of Adult Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma. Delgado, J., Papadouli, I., Sarac, SB., et al.[2021]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05351593

Tafasitamab Plus Lenalidomide in Relapsed CNS ... A phase of research to describe clinical trials that gather more information about a drug's safety and effectiveness by studying different populations and ...

2. 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

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10797539/

Tafasitamab and lenalidomide in large B-cell lymphoma Outcomes in the real-world series were very poor (31% response rate and a median progression-free survival of 1.9 months), suggesting that, for this regimen, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9475241/

Improved Efficacy of Tafasitamab plus Lenalidomide versus ... In RE-MIND2 (NCT04697160), patient-level outcomes from the L-MIND study (NCT02399085) of tafasitamab plus lenalidomide were retrospectively compared with ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123097069

A Phase I/II Study of Tafasitamab Plus Lenalidomide in ... We are studying the off-label use of tafasitamab, in combination with lenalidomide in relapsed CNS lymphomas.

6. canjhealthtechnol.ca canjhealthtechnol.ca/index.php/cjht/article/view/PC0266r/1146

View of Tafasitamab (Minjuvi) The clinical experts thought that patients with CNS involvement of lymphoma, PMBL, or Burkitt lymphoma should not be treated with tafasitamab plus lenalidomide ...