Tafasitamab + Lenalidomide + Venetoclax for Mantle Cell Lymphoma

(V-MIND Trial)

Recruiting at 1 trial location

Overseen By Inbox Mayo Clinic Cancer Studies

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Academic and Community Cancer Research United

Must not be taking: P-gp inhibitors, CYP3A inhibitors

Disqualifiers: Pregnancy, CNS involvement, HIV, 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: 4

Duration: Variable, up to 5 years

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a combination of three drugs—tafasitamab, lenalidomide, and venetoclax—for individuals with mantle cell lymphoma that has recurred or not responded to treatment. Tafasitamab stops cancer growth, lenalidomide boosts the immune system to fight cancer, and venetoclax blocks a protein that helps cancer cells survive. The aim is to determine if these drugs together are more effective at killing cancer cells. Individuals with mantle cell lymphoma that has not improved with previous treatments and who experience visible symptoms or issues from the disease may be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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

The trial protocol does not specify if you need to stop your current medications, but it does mention that you cannot take certain medications like strong CYP3A inhibitors or inducers, and you must avoid grapefruit and similar products. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research has shown that using tafasitamab and lenalidomide together is safe and effective for patients with certain recurring or hard-to-treat cancers, such as diffuse large B-cell lymphoma (DLBCL). In these studies, most patients tolerated the treatment well, and no deaths were linked to treatment side effects, suggesting the combination is relatively safe.

Venetoclax blocks a protein that helps cancer cells survive. It has been used in various cancer treatments and has a known safety record. While side effects can occur, they are usually manageable with medical help.

Although specific data on using tafasitamab, lenalidomide, and venetoclax together for mantle cell lymphoma is lacking, safety results from similar treatments are promising. Prospective participants can feel somewhat confident about the treatment's safety based on these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Tafasitamab, Lenalidomide, and Venetoclax for treating Mantle Cell Lymphoma because this trio targets the cancer in multiple ways. Tafasitamab is an antibody that directly attacks cancer cells by marking them for destruction by the immune system. Lenalidomide boosts the immune response, making it more effective against the cancer. Venetoclax disrupts the cancer cells' ability to survive by targeting a protein called BCL-2, which is often overactive in cancer cells. This multi-pronged approach could potentially be more effective than the current standard treatments, which typically focus on chemotherapy and targeted therapies individually.

What evidence suggests that this trial's treatments could be effective for mantle cell lymphoma?

Research has shown that combining three drugs—tafasitamab, lenalidomide, and venetoclax—might help treat relapsed or refractory mantle cell lymphoma. In this trial, participants will receive this combination treatment. Tafasitamab targets cancer cells to stop their growth. Lenalidomide enhances the immune system's ability to attack cancer cells. Venetoclax blocks a protein called Bcl-2, which cancer cells need to survive. Together, these treatments are believed to kill cancer cells more effectively. Previous patients with similar conditions responded well to these therapies. ^{1 2 3 6 7}

Who Is on the Research Team?

Yucai Wang

Principal Investigator

Academic and Community Cancer Research United

Are You a Good Fit for This Trial?

Adults with relapsed or refractory mantle cell lymphoma, who've had at least one prior treatment and have measurable disease. They must be in relatively good health, with adequate blood counts and organ function, not pregnant, willing to use contraception, and able to take daily aspirin or anticoagulants. Excluded are those recently receiving certain treatments like stem cell transplants or CAR T-cell therapy, those with CNS involvement by MCL or severe concurrent diseases.

Inclusion Criteria

My MCL cancer still shows CD19 presence after previous treatment, unless a biopsy is risky for me.

My condition worsened or didn't improve after at least one treatment.

My disease can be measured by the size of lymph nodes, lesions, spleen, or white blood cell count.

Exclusion Criteria

I am not taking any medications that affect CYP3A4.

I do not have any severe illnesses besides my current condition.

Pregnant or nursing persons

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive tafasitamab intravenously, lenalidomide orally, and venetoclax orally. Patients may undergo lumbar puncture, CT scan, blood sample collection, MRI, tumor biopsy, PET/CT, bone marrow biopsy, and bone marrow aspirate.

Variable, up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up includes CT scans, blood sample collection, and possibly MRI and tumor biopsy.

5 years

Every 3 months for 1 year, every 4 months for 1 year, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Lenalidomide
• Tafasitamab
• Venetoclax

Trial Overview The trial is testing a combination of three drugs: tafasitamab (a monoclonal antibody), lenalidomide (an immunomodulatory agent), and venetoclax (a Bcl-2 inhibitor) for treating mantle cell lymphoma that has returned after treatment or hasn't responded to previous therapies. The goal is to see if this drug combo can more effectively kill cancer cells.

How Is the Trial Designed?

Group I: Treatment (Tafasitamab, lenalidomide, venetoclax) Experimental Treatment 11 Interventions

Patients receive tafasitamab IV, lenalidomide PO and venetoclax PO while on study. Patients may undergo lumbar puncture during screening. Patients undergo CT scan and blood sample collection and may undergo MRI and tumor biopsy on study and during follow-up. Patients undergo PET/CT, bone marrow biopsy, and bone marrow aspirate throughout the study.

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?

Academic and Community Cancer Research United

Lead Sponsor

Trials

54

Recruited

4,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 81 patients with relapsed mantle cell lymphoma (MCL), venetoclax treatment resulted in a 40% overall response rate, with a median progression-free survival of 3.7 months and overall survival of 12.5 months, indicating its efficacy in this high-risk population.

Despite a majority of patients being at low risk for tumor lysis syndrome (TLS), 12.3% experienced TLS, highlighting the need for careful monitoring and mitigation strategies when initiating venetoclax treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter analysis of the outcomes with venetoclax in patients with relapsed mantle cell lymphoma. Sawalha, Y., Goyal, S., Switchenko, JM., et al.[2023]

In a study of 22 relapsed/refractory multiple myeloma patients, low-dose venetoclax (≤250 mg/day) combined with bortezomib, daratumumab, and dexamethasone showed an impressive overall response rate of 80% in patients with the t(11;14) chromosomal marker, indicating its efficacy as a salvage therapy.

The low-dose regimen significantly reduced the incidence of serious adverse events, particularly infections, which are commonly associated with higher doses of venetoclax, suggesting a safer treatment option for this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low dose venetoclax in combination with bortezomib, daratumumab, and dexamethasone for the treatment of relapsed/refractory multiple myeloma patients-a single-center retrospective study. Regidor, B., Goldwater, MS., Wang, J., et al.[2021]

In a study of 24 patients with relapsed mantle cell lymphoma (MCL) who had undergone multiple prior therapies, venetoclax treatment resulted in a 50% overall response rate and a 21% complete response rate, with a median follow-up of 17 months.

Genomic analysis revealed that resistance to venetoclax is linked to mutations in non-BCL2 genes, with specific alterations like SMARCA4 and KMT2C/D emerging after treatment progression, indicating a need for further research into combination therapies and the mechanisms of resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of venetoclax in high risk relapsed mantle cell lymphoma (MCL) - outcomes and mutation profile from venetoclax resistant MCL patients. Zhao, S., Kanagal-Shamanna, R., Navsaria, L., et al.[2020]

Venetoclax, a BCL2-targeting drug, shows promising anticancer activity in mantle cell lymphoma (MCL), but resistance mechanisms involving proapoptotic proteins BIM and NOXA complicate its effectiveness.

Combining venetoclax with the MCL1 inhibitor S63845 resulted in synthetic lethality in patient-derived xenografts of relapsed MCL, suggesting this combination could be a novel treatment strategy for patients with chemoresistant MCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cotargeting of BCL2 with Venetoclax and MCL1 with S63845 Is Synthetically Lethal In Vivo in Relapsed Mantle Cell Lymphoma. Prukova, D., Andera, L., Nahacka, Z., 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 a multicenter study of 28 patients with untreated mantle cell lymphoma (MCL), the combination of lenalidomide, rituximab, and venetoclax demonstrated a high overall response rate of 96% and a complete response rate of 86%, indicating strong efficacy for this treatment regimen.

The treatment was found to be safe, with no dose-limiting toxicities reported, although common side effects included neutropenia and thrombocytopenia, suggesting that this combination could be a promising option for patients who are ineligible for transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding venetoclax to lenalidomide and rituximab is safe and effective in patients with untreated mantle cell lymphoma. Phillips, TJ., Bond, D., Takiar, R., et al.[2023]

The maximum tolerated dose (MTD) of lenalidomide when combined with rituximab for treating relapsed or refractory mantle-cell lymphoma (MCL) was determined to be 20 mg, with the combination showing a manageable safety profile despite some grade 3-4 hematological toxicities.

In a phase 2 trial involving 44 patients, the combination therapy resulted in a 57% overall response rate, with 36% achieving a complete response and a median overall survival of 24.3 months, indicating its efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with rituximab for patients with relapsed or refractory mantle-cell lymphoma: a phase 1/2 clinical trial. Wang, M., Fayad, L., Wagner-Bartak, N., 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, 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05910801

Study Details | NCT05910801 | Tafasitamab, Lenalidomide ... Giving tafasitamab, lenalidomide and venetoclax together may kill cancer cells more efficiently in patients with relapsed or refractory mantle cell lymphoma.

2. mayo.edu mayo.edu/research/clinical-trials/cls-20561548

Tafasitamab, Lenalidomide and Venetoclax for the ... The purpose of this study is to determine how well tafasitamab, lenalidomide and venetoclax work in treating patients with mantle cell lymphoma ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12248784/

Next-Generation Therapies in Mantle Cell Lymphoma (MCL) This review aims to make an overview on the novel treatment emerging in this tough setting, such as new non-covalent BTKi molecules and novel monoclonal ...

4. 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%), ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8363059/

Tafasitamab for the treatment of relapsed or refractory diffuse ... Tafasitamab, an anti-CD19 monoclonal antibody, in combination with lenalidomide has demonstrated promising efficacy for patients with R/R DLBCL who are ...

6. monjuvihcp.com monjuvihcp.com/dlbcl/study-design

DLBCL Study Design - MONJUVI® (tafasitamab-cxix) HCP Efficacy and safety of MONJUVI in combination with lenalidomide followed by MONJUVI monotherapy were evaluated in adults with R/R DLBCL after 1 to 3 prior ...

7. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incyte-late-breaking-tafasitamab-monjuvir-data-ash-2024

Incyte Late-Breaking Tafasitamab (Monjuvi®) Data at ASH ... “In the Phase 3 inMIND trial, tafasitamab demonstrated impressive efficacy and safety for treating certain patients with follicular lymphoma, ...