Combination Therapy for B-Cell Lymphoma

Overseen By Jason Westin

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Aspirin

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: HIV, Hepatitis B, Hepatitis C, 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: Unknown

36 Participants Needed

Trial Summary

What is the purpose of this trial?

To learn if giving mosunetuzumab in combination with polatuzumab vedotin, tafasitamab, and lenalidomide can help to control relapsed/refractory FL and DLBCL.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have regular treatment with corticosteroids or systemic immunosuppressive medications within 2 weeks before starting the trial, and you must not have had chemotherapy, immunotherapy, or radiotherapy shortly before the trial begins.

What data supports the effectiveness of the drug combination therapy for B-cell lymphoma?

Research shows that polatuzumab vedotin, a component of the combination therapy, has demonstrated effectiveness in treating relapsed or refractory large B-cell lymphoma, achieving a response in 44% of patients in a study, including complete remission in 14% of cases. ^{1 2 3 4 5}

Is the combination therapy for B-cell lymphoma safe for humans?

Polatuzumab vedotin, a key component of the combination therapy, has been studied in various clinical trials and is generally considered safe, with common side effects including low blood cell counts and nerve damage. The risk of developing an immune response to the drug is low, and it has been approved for use in certain types of B-cell lymphoma, indicating an acceptable safety profile. ^{1 3 4 5 6}

What makes the combination therapy for B-Cell Lymphoma unique?

This combination therapy for B-Cell Lymphoma is unique because it combines multiple drugs, including lenalidomide, mosunetuzumab, polatuzumab vedotin, and tafasitamab, each with different mechanisms of action. Polatuzumab vedotin, for example, is an antibody-drug conjugate that targets the CD79b component of B-cells, delivering a potent anti-cancer agent directly to the cancer cells, which is a novel approach compared to traditional chemotherapy. ^{1 3 6 7 8}

Research Team

Jason Westin

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults with relapsed B-cell non-Hodgkin lymphoma, including Follicular Lymphoma and diffuse large B-cell lymphoma, who have seen their disease progress after at least one prior treatment. Participants must be over 18, not pregnant or breastfeeding, willing to use contraception and join the Revlimid REMS program.

Inclusion Criteria

I have been diagnosed with a type of lymphoma called CD20+ Follicular Lymphoma grades 1-3a.

My blood counts are within a healthy range.

Patients in each component must be able and willing to provide written informed consent and to comply with the study protocol

Exclusion Criteria

I do not have severe nerve pain or damage.

I have not received any live vaccines in the last 28 days.

My lymphoma has spread to my brain or spinal cord.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run In

During the safety run-in, the study team will first test a recommended dose of mosunetuzumab, polatuzumab vedotin, tafasitamab, and lenalidomide

4-6 weeks

Dose Expansion Cohort

Participants will receive mosunetuzumab, polatuzumab vedotin, tafasitamab, and lenalidomide at the dose level that was found tolerated in the safety run-in

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Lenalidomide
• Mosunetuzumab
• Polatuzumab vedotin
• Tafasitamab

Trial Overview The trial is testing a combination of four drugs: Mosunetuzumab, Polatuzumab vedotin, Tafasitamab, and Lenalidomide in patients whose B-cell NHL has returned after previous treatments. It aims to see if this drug combo can better control the disease.

Participant Groups

Group I: Safety Run In Experimental Treatment 4 Interventions

During the safety run-in, the study team will first test a recommended dose of mosunetuzumab, polatuzumab vedotin, tafasitamab, and lenalidomide.

Group II: Dose Expansion Cohort Experimental Treatment 4 Interventions

Participants will receive mosunetuzumab, polatuzumab vedotin, tafasitamab, and lenalidomide at the dose level that was found tolerated in the safety run-in.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

The Pola-G-Len combination therapy demonstrated a high complete response rate of 63% and an overall objective response rate of 76% in patients with relapsed or refractory follicular lymphoma, indicating its potential efficacy in this challenging patient population.

The study identified a recommended phase 2 dose of 1.4 mg/kg polatuzumab vedotin plus 20 mg lenalidomide, with manageable safety profiles, although common adverse events included neutropenia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed or refractory follicular lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study. Diefenbach, C., Kahl, BS., McMillan, A., et al.[2022]

In a study of patients with transplantation-ineligible relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), the combination of polatuzumab vedotin with bendamustine and rituximab (pola-BR) resulted in a significantly higher complete response (CR) rate of 40% compared to 17.5% with bendamustine and rituximab alone, indicating improved efficacy.

Patients receiving pola-BR also experienced longer progression-free survival (9.5 months vs. 3.7 months) and overall survival (12.4 months vs. 4.7 months), although there were higher rates of certain side effects like neutropenia and peripheral neuropathy, which were mostly manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Sehn, LH., Herrera, AF., Flowers, CR., et al.[2021]

In a study involving 85 patients with untreated diffuse large B-cell lymphoma, the combination of polatuzumab vedotin with standard chemotherapy (R-CHP or G-CHP) showed promising preliminary efficacy, with 89% of patients achieving an overall response and 77% achieving a complete response.

The safety profile of polatuzumab vedotin was manageable, with common adverse events including neutropenia and peripheral neuropathy, leading to the establishment of a recommended phase 2 dose of 1.8 mg/kg for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b-2 study. Tilly, H., Morschhauser, F., Bartlett, NL., et al.[2023]

In a study of 57 patients with relapsed large B-cell lymphoma after CAR T-cell therapy, polatuzumab vedotin (PV) showed a response rate of 44%, with 14% achieving complete remission, indicating its potential efficacy in this challenging patient population.

The median progression-free survival was only 10 weeks, and factors like bone marrow involvement and high lactate dehydrogenase levels were linked to shorter survival, highlighting the need for further research on treatment resistance and consolidation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter retrospective study of polatuzumab vedotin in patients with large B-cell lymphoma after CAR T-cell therapy. Gouni, S., Rosenthal, AC., Crombie, JL., et al.[2023]

Polatuzumab vedotin (POLIVY®) is an effective treatment for adult patients with diffuse large B-cell lymphoma, approved after showing significant anti-cancer activity by delivering a potent drug directly to B cells.

The incidence of anti-drug antibodies (ADA) against polatuzumab vedotin is low, likely due to its mechanism of action that targets and kills B cells, which minimizes immune response and supports a favorable benefit/risk profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. Dere, RC., Beardsley, RL., Lu, D., et al.[2023]

Polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, has been approved for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in patients who are ineligible for transplant, showing a complete response rate of 40% compared to 18% for standard treatment with bendamustine and rituximab (BR).

The most common side effects associated with polatuzumab vedotin treatment include cytopenias (a reduction in blood cells) and peripheral neuropathy, highlighting the need for monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin to treat relapsed or refractory diffuse large B-cell lymphoma, in combination with bendamustine plus rituximab. Amaya, ML., Jimeno, A., Kamdar, M.[2021]

Polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, has demonstrated significant clinical effectiveness in treating follicular and diffuse large B-cell lymphoma (DLBCL), and is FDA-approved for use with bendamustine and rituximab in patients with relapsed or refractory DLBCL.

The review highlights the ongoing research and potential future applications of polatuzumab in the treatment of B-cell non-Hodgkin lymphoma, indicating its importance in expanding treatment options for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of Polatuzumab Vedotin in the Treatment of Patients with Relapsed/Refractory Non-Hodgkin Lymphoma: A Brief Report on the Emerging Clinical Data. Sawalha, Y., Maddocks, K.[2022]

In the phase III AUGMENT trial, lenalidomide combined with rituximab significantly improved progression-free survival in patients with relapsed or refractory follicular lymphoma compared to placebo, showing particular benefit for elderly patients.

Lenalidomide has an acceptable safety profile, although it can cause more frequent cases of severe neutropenia, which can be managed with dosage adjustments and growth factor support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: A Review in Previously Treated Follicular Lymphoma. Blair, HA.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed or refractory follicular lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study. [2022]

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

Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b-2 study. [2023]

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

A multicenter retrospective study of polatuzumab vedotin in patients with large B-cell lymphoma after CAR T-cell therapy. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. [2023]

6. Spain pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin to treat relapsed or refractory diffuse large B-cell lymphoma, in combination with bendamustine plus rituximab. [2021]

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

Profile of Polatuzumab Vedotin in the Treatment of Patients with Relapsed/Refractory Non-Hodgkin Lymphoma: A Brief Report on the Emerging Clinical Data. [2022]

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

Lenalidomide: A Review in Previously Treated Follicular Lymphoma. [2021]