Combination Therapy for B-Cell Lymphoma

Recruiting in Palo Alto (17 mi)

+7 other locations

Overseen by Joseph M. Tuscano

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents

Disqualifiers: Plasmablastic lymphoma, Active infection, Pregnancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of mosunetuzumab when given together with polatuzumab vedotin and lenalidomide in treating patients with diffuse large B-cell lymphoma (DLBCL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Mosunetuzumab and polatuzumab vedotin are monoclonal antibodies that may interfere with the ability of cancer cells to grow and spread. Polatuzumab, linked to a toxic agent called vedotin, attaches to CD79B positive cancer cells in a targeted way and delivers vedotin to kill them. Lenalidomide may stimulate or suppress the immune system in different ways and stop cancer cells from growing and by preventing the growth of new blood vessels that cancer cells need to grow. Giving mosunetuzumab with polatuzumab vedotin and lenalidomide may work better in treating patients with relapsed/refractory DLBCL.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, some concurrent cancer therapies are allowed, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination therapy for B-Cell Lymphoma?

Polatuzumab vedotin, a component of the combination therapy, has shown effectiveness in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) when combined with other drugs like bendamustine and rituximab, achieving a higher complete response rate compared to treatment without it. Additionally, lenalidomide has shown activity in combination with other drugs for follicular lymphoma, suggesting potential benefits in B-cell lymphoma treatment. ^{1 2 3 4 5}

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

The combination therapy involving polatuzumab vedotin, lenalidomide, and other drugs has shown acceptable safety in clinical trials for B-cell lymphomas, with a low incidence of immune reactions and manageable side effects like neutropenia (low white blood cell count) and fatigue. ^{1 6 7 8 9}

What makes the combination therapy of Lenalidomide, Mosunetuzumab, and Polatuzumab Vedotin unique for treating B-Cell Lymphoma?

This combination therapy is unique because it combines three different mechanisms: Lenalidomide boosts the immune system, Mosunetuzumab targets specific cancer cells, and Polatuzumab Vedotin delivers a toxic agent directly to cancer cells. This multi-faceted approach may enhance the overall effectiveness against B-Cell Lymphoma compared to traditional treatments. ^{1 10 11 12 13}

Research Team

Joseph M. Tuscano

Principal Investigator

City of Hope Comprehensive Cancer Center LAO

Eligibility Criteria

This trial is for adults with Diffuse Large B-Cell Lymphoma that has returned or didn't respond to previous treatments. They should have a life expectancy of at least 12 weeks, measurable disease by scans, and an ECOG performance status of 2 or better. Patients who've had CAR T-cell therapy or relapsed after other therapies may join, except those under 18 years old.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

My DLBCL has not improved after at least one treatment, except if I'm getting CAR T therapy as my second treatment and have a specific score.

Cohort A must have had an incomplete response or Deauville score of 3 or 4 at 90 days post CAR-T therapy, while cohort B comprises patients who relapsed after one or more previous treatment regimens (for example relapse following day 90 from CAR-T, or those that experienced recurrence on other therapies but were ineligible for either CAR-T or autologous hematopoietic cell transplantation).

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mosunetuzumab, polatuzumab vedotin, and lenalidomide. Mosunetuzumab is administered IV on days 1, 8, and 15 of cycle 1 and then day 1 of each subsequent cycle. Polatuzumab vedotin is administered IV on day 1 for 6 cycles. Lenalidomide is taken orally on days 1-21 for 8 cycles in patients who achieve CR or up to 17 cycles.

8-17 cycles (28 days per cycle)

Multiple visits for IV administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up includes PET/CT scans and blood sample collection.

Every 3-6 months for 2 years

Treatment Details

Interventions

• Lenalidomide (Other)
• Mosunetuzumab (Monoclonal Antibodies)
• Polatuzumab Vedotin (Monoclonal Antibodies)

Trial Overview The trial tests a combination of three drugs: Mosunetuzumab, Polatuzumab Vedotin, and Lenalidomide in patients with relapsed/refractory DLBCL. It aims to find the safest doses and observe how well these drugs work together against cancer cells.

Participant Groups

Group I: Treatment (mosunetuzumab, polatuzumab vedotin, lenalidomide) Experimental Treatment 6 Interventions

Patients receive mosunetuzumab IV over 2-4 hours on days 1, 8, and 15 of cycle 1 and then day 1 of each subsequent cycle. Treatment repeats every 28 days for 8 cycles in patients who achieve a CR or up to 17 cycles for patients with a PR or SD in the absence of disease progression or unacceptable toxicity. Patients also receive polatuzumab vedotin IV over 30-90 minutes on day 1 for 6 cycles and lenalidomide PO on days 1-21 for 8 cycles in patients who achieve CR or up to 17 cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo PET/CT and blood sample collection throughout the study.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Northwestern University Chicago, IL

University of Oklahoma Health Sciences Center Oklahoma City, OK

City of Hope Comprehensive Cancer Center LAO Duarte, CA

University of California Davis Comprehensive Cancer Center Sacramento, CA

More Trial Locations

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14080

Patients Recruited

41,180,000+

Findings from Research

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]

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]

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]

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]

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]

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin, an anti-CD79b antibody-drug conjugate for the treatment of relapsed/refractory diffuse large B-cell lymphoma. Camus, V., Tilly, H.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of polatuzumab vedotin in combination with R/G-CHP in patients with B-cell non-Hodgkin lymphoma. Shemesh, CS., Agarwal, P., Lu, T., et al.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. Budde, LE., Olszewski, AJ., Assouline, S., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of polatuzumab vedotin for the treatment of patients with diffuse large B-cell lymphoma. Walji, M., Assouline, S.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in follicular lymphoma. Flowers, CR., Leonard, JP., Fowler, NH.[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

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

3. 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]

4. 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]

5. 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]

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin, an anti-CD79b antibody-drug conjugate for the treatment of relapsed/refractory diffuse large B-cell lymphoma. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of polatuzumab vedotin in combination with R/G-CHP in patients with B-cell non-Hodgkin lymphoma. [2020]

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

Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. [2023]

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

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

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

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

12. England pubmed.ncbi.nlm.nih.gov

An evaluation of polatuzumab vedotin for the treatment of patients with diffuse large B-cell lymphoma. [2021]

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

Lenalidomide in follicular lymphoma. [2021]