Tafasitamab + Lenalidomide + Venetoclax for Mantle Cell Lymphoma

(V-MIND Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Yucai Wang

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase II trial tests how well tafasitamab, lenalidomide and venetoclax work in treating patients with mantle cell lymphoma that has come back (after a period of improvement) (relapsed) or that has not responded to previous treatment (refractory). Tafasitamab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Lenalidomide is in a class of medications called immunomodulatory agents. It works by helping the immune system kill cancer cells. Venetoclax is in a class of medications called B-cell lymphoma-2 (Bcl-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving tafasitamab, lenalidomide and venetoclax together may kill cancer cells more efficiently in patients with relapsed or refractory mantle cell lymphoma.

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.

What data supports the effectiveness of the drug combination Tafasitamab, Lenalidomide, and Venetoclax for Mantle Cell Lymphoma?

Research shows that adding venetoclax to lenalidomide and rituximab is safe and effective for untreated mantle cell lymphoma, with high response rates. Additionally, venetoclax has shown effectiveness in relapsed mantle cell lymphoma, and tafasitamab plus lenalidomide has been effective in other similar lymphomas, suggesting potential benefits for this combination. ^{1 2 3 4 5}

Is the combination of Tafasitamab, Lenalidomide, and Venetoclax safe for humans?

The combination of Lenalidomide and Venetoclax has been found to be safe in patients with untreated mantle cell lymphoma, with common side effects being low white blood cell counts (neutropenia) and low platelet counts (thrombocytopenia). Tafasitamab combined with Lenalidomide is also considered safe for treating certain types of lymphoma, with regulatory approvals supporting its use. ^{1 2 3 4 6}

What makes the drug combination of Tafasitamab, Lenalidomide, and Venetoclax unique for treating mantle cell lymphoma?

This drug combination is unique because it combines three targeted therapies that work in different ways to attack cancer cells: Tafasitamab targets CD19 on B-cells, Lenalidomide modulates the immune system, and Venetoclax inhibits BCL2, a protein that helps cancer cells survive. This combination aims to enhance treatment effectiveness by using multiple mechanisms to fight the cancer. ^{2 5 7 8 9}

Research Team

Yucai Wang

Principal Investigator

Academic and Community Cancer Research United

Eligibility Criteria

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

I am 18 years old or older.

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.

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

Trial Timeline

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

Treatment Details

Interventions

• Lenalidomide (Immunomodulatory Agent)
• Tafasitamab (Monoclonal Antibodies)
• Venetoclax (Bcl-2 Inhibitor)

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.

Participant Groups

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Mayo Clinic in Rochester Rochester, MN

M D Anderson Cancer Center Houston, TX

Who Is Running the Clinical Trial?

Academic and Community Cancer Research United

Lead Sponsor

Trials

54

Patients Recruited

4,900+

National Cancer Institute (NCI)

Collaborator

Trials

14080

Patients Recruited

41,180,000+

Findings from Research

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]

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]

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]

References

1. United States 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. [2022]

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

Adding venetoclax to lenalidomide and rituximab is safe and effective in patients with untreated mantle cell lymphoma. [2023]

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

Tafasitamab: First Approval. [2022]

4. 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]

5. United States 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. [2020]

6. Germany 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. [2021]

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

Cotargeting of BCL2 with Venetoclax and MCL1 with S63845 Is Synthetically Lethal In Vivo in Relapsed Mantle Cell Lymphoma. [2020]

8. England 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. [2023]

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

A multicenter analysis of the outcomes with venetoclax in patients with relapsed mantle cell lymphoma. [2023]