Tafasitamab + Lenalidomide/ICE for Large B-Cell Lymphoma

Overseen by David A. Bond, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: David Bond, MD

Must not be taking: Anti-CD19, Lenalidomide

Disqualifiers: CNS involvement, HIV, Hepatitis, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This phase II clinical trial evaluates tafasitamab and lenalidomide followed by tafasitamab and the carboplatin, etoposide and ifosfamide (ICE) regimen as salvage therapy for transplant eligible patients with large B-cell lymphoma that has come back (relapsed) or has not responded to treatment (refractory). Tafasitamab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Lenalidomide may have antineoplastic activity which may help block the formation of growths that may become cancer. Drugs used in chemotherapy, such as carboplatin, etoposide and ifosfamide work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving tafasitamab and lenalidomide followed by ICE may be a better treatment for patients with relapsed or refractory large B-cell lymphomas.

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

The trial protocol does not specify whether you need to stop taking your current medications. However, prior lymphoma therapy should be completed more than two weeks before starting the trial, except for corticosteroids used for symptom relief.

What data supports the effectiveness of the drug combination Tafasitamab and Lenalidomide for treating large B-cell lymphoma?

Research shows that the combination of Tafasitamab and Lenalidomide is effective for patients with relapsed or refractory diffuse large B-cell lymphoma, with a 57.5% overall response rate and a 41.3% complete response rate in a study. This combination has shown long-term benefits and manageable side effects, making it a promising option for patients who cannot undergo stem cell transplants. ^{1 2 3 4 5}

Is the combination of Tafasitamab and Lenalidomide safe for treating large B-cell lymphoma?

The combination of Tafasitamab and Lenalidomide has been shown to be generally safe and well-tolerated in patients with relapsed or refractory diffuse large B-cell lymphoma, with manageable side effects and no new safety concerns reported in long-term studies. ^{1 2 4 6 7}

What makes the drug combination of Tafasitamab and Lenalidomide unique for treating large B-cell lymphoma?

This drug combination is unique because it involves tafasitamab, an anti-CD19 immunotherapy, which is used with lenalidomide to treat patients who are not eligible for stem cell transplants. It is the first therapy approved as a second-line treatment for relapsed or refractory diffuse large B-cell lymphoma, offering a new option for patients with limited treatment choices. ^{1 2 4 5 6}

Research Team

David A. Bond, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with certain types of large B-cell lymphoma that has relapsed or hasn't responded to treatment. They must have had one prior chemo-immunotherapy, be eligible for a transplant, and able to consent. Participants need adequate organ function and no history of significant heart disease, uncontrolled infection, or other cancers that could interfere.

Inclusion Criteria

Serum total bilirubin =< 1.5 x upper limit of normal (ULN) (except in patients with Gilbert Syndrome who can have total bilirubin < 3.0 mg/dL)

My hemoglobin level is at least 8.0 g/dL, unless it's low due to my lymphoma.

My diagnosis is a specific type of advanced B cell lymphoma.

Exclusion Criteria

I finished my lymphoma treatment over two weeks ago, except for steroids for symptom relief.

Known contraindication to any medication in the treatment plan, including known hypersensitivity

My lymphoma has spread to my brain or spinal cord.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tafasitamab IV, lenalidomide PO, etoposide IV, ifosfamide IV, and carboplatin IV. Imaging and blood sample collection are conducted throughout the study.

8-16 weeks

Follow-up

Participants are monitored for safety, effectiveness, and progression-free survival after treatment.

Up to 2 years

Long-term follow-up

Participants are monitored for overall survival and incidence of adverse events.

Up to 5 years

Treatment Details

Interventions

• Carboplatin (Alkylating agents)
• Etoposide (Topoisomerase II inhibitors)
• Ifosfamide (Alkylating agents)
• Lenalidomide (Immunomodulatory Agent)
• Tafasitamab (Monoclonal Antibodies)

Trial Overview The study tests tafasitamab plus lenalidomide followed by ICE chemotherapy (carboplatin, etoposide, ifosfamide) as salvage therapy in patients suitable for transplants. Tafasitamab is an antibody against cancer cells; lenalidomide may block tumor growth; ICE kills or stops cancer cell division.

Participant Groups

Group I: Treatment (tafasitamab, lenalidomide, ICE regimen) Experimental Treatment 9 Interventions

Patients receive tafasitamab IV, lenalidomide PO, etoposide IV, ifosfamide IV and carboplatin IV on study. Patients undergo PET or CT, and undergo blood sample collection throughout the study. Patients may undergo tissue biopsy on study.

Who Is Running the Clinical Trial?

David Bond, MD

Lead Sponsor

Trials

4

Recruited

110+

Findings from Research

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]

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]

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 phase 2 study involving 81 patients with relapsed or refractory diffuse large B-cell lymphoma, the combination of tafasitamab and lenalidomide resulted in a 60% objective response rate, with 43% achieving a complete response, indicating significant antitumor activity.

The treatment was generally well tolerated, although serious adverse events occurred in 51% of patients, with neutropenia being the most common, suggesting that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Salles, G., Duell, J., González Barca, E., et al.[2020]

A 75-year-old man with high-risk transformed Waldenström macroglobulinemia (WM) showed a complete and durable response to tafasitamab plus lenalidomide (TAF/LEN), indicating potential efficacy for this combination therapy in treating transformed WM.

This case suggests that TAF/LEN, which is approved for relapsed diffuse large-cell lymphoma, may also be a promising and tolerable treatment option for patients with transformed WM, warranting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transformed Waldenström Macroglobulinemia Responsive to Tafasitamab Plus Lenalidomide: A Case Report. Nasir, SA., Pandya, D., Wojkiewicz, S., et al.[2023]

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 is an orally bioavailable immunomodulator that has shown significant antitumor activity in treating various types of B-cell lymphomas, including mantle cell lymphoma and diffuse large B-cell lymphoma.

The drug has a favorable safety profile and is effective both as a standalone treatment and in combination with other therapies, marking a shift from traditional chemotherapy approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of lenalidomide in non-Hodgkin lymphoma. Galanina, N., Petrich, A., Nabhan, C.[2019]

References

1. Italy 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. [2023]

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

Tafasitamab: First Approval. [2022]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. [2020]

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

Transformed Waldenström Macroglobulinemia Responsive to Tafasitamab Plus Lenalidomide: A Case Report. [2023]

6. Italy 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. [2021]

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

The evolving role of lenalidomide in non-Hodgkin lymphoma. [2019]