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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combination of four drugs—mosunetuzumab, polatuzumab vedotin, tafasitamab, and lenalidomide—can control two types of B-cell lymphoma that have returned or stopped responding to treatment. These lymphomas are follicular lymphoma and diffuse large B-cell lymphoma. Individuals whose lymphoma has recurred or not responded after at least one previous treatment may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that the combination of mosunetuzumab, polatuzumab vedotin, tafasitamab, and lenalidomide is being tested for safety in treating B-cell lymphoma. Previous studies found that polatuzumab vedotin, when combined with other treatments, generally has manageable or mild side effects.

In this trial, researchers first tested doses to determine a well-tolerated level. This suggests the treatment is likely safe, as it passed initial safety checks. However, while these medicines have been generally well-tolerated in past studies, individual reactions can vary. Prospective participants should discuss any concerns with the trial team before joining. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this combination therapy for B-cell lymphoma because it brings together four powerful agents: lenalidomide, mosunetuzumab, polatuzumab vedotin, and tafasitamab. Unlike standard treatments that may rely on single agents or chemotherapy, this combo leverages multiple mechanisms. Mosunetuzumab is a bispecific antibody that directs the immune system to attack cancer cells, while polatuzumab vedotin delivers a toxic payload directly to lymphoma cells. Tafasitamab enhances the immune system's ability to target and destroy cancerous B-cells. This multi-faceted approach has the potential to improve outcomes by attacking the cancer from several angles at once.

What evidence suggests that this trial's treatments could be effective for B-Cell Lymphoma?

This trial will evaluate the combination of mosunetuzumab, polatuzumab vedotin, tafasitamab, and lenalidomide for B-cell lymphoma. Studies have shown that mosunetuzumab alone can lead to complete recovery in 24% of patients with hard-to-treat diffuse large B-cell lymphoma (DLBCL). Combining mosunetuzumab with polatuzumab vedotin has produced strong and lasting improvements, making it a promising option for those ineligible for a transplant. Research also shows that tafasitamab, when paired with lenalidomide, can increase the body's ability to fight cancer cells by 3 to 5 times. These findings suggest that using these drugs together could effectively manage lymphoma that has returned or is not responding to treatment. ^{1 6 7 8 9}

Who Is on the Research Team?

Jason Westin

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10463194/

Mosunetuzumab monotherapy is active and tolerable in ... Mosunetuzumab is active as a single agent and yields CRs in 24% of heavily pretreated patients with R/R DLBCL.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05615636

NCT05615636 | A Phase II Trial of Mosunetuzumab ... Primary Objectives: To determine the safety of mosunetuzumab, polatuzumab vedotin, tafasitamab, and lenalidomide in relapsed/refractory NHL.

3. nature.com nature.com/articles/s41591-023-02726-5

Mosunetuzumab with polatuzumab vedotin in relapsed or ... Mosunetuzumab plus polatuzumab vedotin has a favorable safety profile with highly durable responses suitable as second-line therapy in transplant-ineligible ...

4. ashpublications.org ashpublications.org/bloodadvances/article/7/17/4926/495381/Mosunetuzumab-monotherapy-is-active-and-tolerable

Mosunetuzumab monotherapy is active and tolerable in ... Key Points. Mosunetuzumab is active as a single agent and yields CRs in 24% of heavily pretreated patients with R/R DLBCL.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10841029/

Tafasitamab for the treatment of patients with diffuse large B ... Results of an in vitro study showed that pre-treatment of macrophages with lenalidomide enhanced tafasitamab-associated cytotoxicity by 3–5 fold ...

6. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2022-0459.html

A phase II trial of Mosunetuzumab, Polatuzumab ... To learn if giving mosunetuzumab in combination with polatuzumab vedotin, tafasitamab, and lenalidomide can help to control relapsed/refractory FL and DLBCL.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8728095/

Novel biologic therapies in relapsed or refractory diffuse ... Patients with diffuse large B-cell lymphoma who have refractory or relapsed disease following first line treatment have a poor prognosis when treated with ...

8. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/s13045-020-01011-z

New agents and regimens for diffuse large B cell lymphoma Giving the significant clinical activities and manageable safety profiles of polatuzumab vedotin, additional evaluation of polatuzumab vedotin ...

9. go.drugbank.com go.drugbank.com/conditions/DBCOND0028221

Diffuse Large B-Cell Lymphoma (DLBCL) ... A Study to Evaluate the Efficacy and Safety of Polatuzumab Vedotin in Combination With Bendamustine and Rituximab Compared With Bendamustine and Rituximab Alone ...