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

Trial Summary

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}

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.

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

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

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
• 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.

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.

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+

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]

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 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 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]

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]

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]

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]

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]

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]