Combination Therapy for Lymphoma

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Organ transplant, Active infection, Cardiac disease, 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: 6

41 Participants Needed

Trial Summary

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy for lymphoma symptom control, it must be reduced to 10 mg/day prednisone or equivalent. Please discuss your specific medications with the study team.

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

The combination of rituximab with chemotherapy has been shown to improve outcomes in lymphoma, including better response rates and survival. Rituximab, when used with other drugs like ifosfamide and etoposide, has been effective in treating relapsed or resistant non-Hodgkin's lymphoma. ^{1 2 3 4 5}

Is the combination therapy for lymphoma generally safe in humans?

The combination therapy involving drugs like rituximab, etoposide, and ifosfamide has been studied in various types of lymphoma and is generally considered safe, though it can cause side effects like myelosuppression (a decrease in bone marrow activity leading to fewer blood cells). No drug-related deaths were reported in the studies, indicating an acceptable level of safety. ^{6 7 8 9 10}

What makes the combination therapy for lymphoma unique?

This combination therapy for lymphoma is unique because it includes polatuzumab vedotin, a targeted therapy that delivers a toxic agent directly to cancer cells, along with rituximab, which is a monoclonal antibody that targets CD20 on B-cells. This approach aims to enhance the effectiveness of traditional chemotherapy drugs like carboplatin, etoposide, and ifosfamide, potentially improving outcomes for patients with relapsed or refractory lymphoma. ^{2 3 4 11 12}

What is the purpose of this trial?

This trial studies a combination of drugs to treat patients with diffuse large B-cell lymphoma that has come back or did not respond to previous treatments. The treatment includes a targeted drug that delivers a toxin to cancer cells, an antibody that stops cancer growth, and chemotherapy drugs that kill or stop the division of cancer cells. The goal is to see if this combination is safe and effective.

Research Team

Alex F Herrera

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults with relapsed or refractory diffuse large B-cell lymphoma who have had one prior treatment including CD20-directed immunotherapy and chemotherapy. They must be in good enough health to undergo high-dose chemotherapy followed by a stem cell transplant, not have severe allergies to similar drugs, no active infections or other cancers, and agree to use birth control.

Inclusion Criteria

If unavailable, exceptions may be granted with study principal investigator (PI) approval

Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

Documented informed consent of the participant and/or legally authorized representative

Exclusion Criteria

I have never had, nor do I currently have, a brain infection known as PML.

I am not pregnant or breastfeeding.

You have had serious allergic reactions to similar drugs or substances like the ones being used in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Salvage Therapy

Patients receive polatuzumab vedotin, rituximab, etoposide, carboplatin, and ifosfamide. Treatment repeats every 21 days for up to 2-3 cycles.

6-9 weeks

3-4 visits (in-person)

Consolidation Therapy

Within 30-60 days after ASCT, patients receive polatuzumab vedotin. Treatment repeats every 21 days for up to 3-4 cycles.

9-12 weeks

3-4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 2 years

Periodic visits

Treatment Details

Interventions

• Carboplatin
• Etoposide
• Ifosfamide
• Polatuzumab Vedotin
• Rituximab

Trial Overview The PolaR-ICE trial tests a combination of polatuzumab vedotin (an antibody-drug conjugate), rituximab (an antibody), and chemotherapy agents ifosfamide, carboplatin, and etoposide as initial salvage therapy. It aims to see if this mix can better kill cancer cells in patients whose disease returned or resisted previous treatment.

Participant Groups

Group I: Treatment (PolaR-ICE) Experimental Treatment 5 Interventions

SALVAGE THERAPY: Patients receive polatuzumab vedotin IV on day 1, rituximab IV on day 1, etoposide IV on days 1-3, carboplatin IV on day 2, and ifosfamide IV on day 2 or days 1-3. Treatment repeats every 21 days for up to 2-3 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response, partial response or stable disease by C2D15 may receive 1 additional cycle of PolaR-ICE IV. CONSOLIDATION THERAPY: Within 30-60 days after ASCT, patients receive polatuzumab vedotin IV on day 1. Treatment repeats every 21 days for up to 3-4 cycles in the absence of disease progression or unacceptable toxicity.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Salvage chemotherapy followed by high-dose therapy and autologous stem cell transplantation is the standard treatment for relapsed diffuse large B-cell lymphoma, but the addition of rituximab has improved outcomes after first-line treatment and relapses.

The CORAL trial found no significant difference in response rates between two salvage regimens (R-ICE and R-DHAP), and identified that factors like early relapse and certain genetic markers significantly affect survival, indicating that over 70% of patients may not benefit from standard salvage therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there any role for transplantation in the rituximab era for diffuse large B-cell lymphoma? Gisselbrecht, C.[2022]

Rituximab is highly effective for treating low-grade CD20+ lymphoma, especially when combined with chemotherapy, which is the standard treatment for follicular lymphoma (FL).

The efficacy of rituximab can be enhanced by combining it with biological agents like interferon-alpha-2a, bortezomib, or lenalidomide, but more research is needed to determine the best combinations and timing of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological therapy doublets: pairing rituximab with interferon, lenalidomide, and other biological agents in patients with follicular lymphoma. Kimby, E.[2021]

The addition of rituximab to standard chemotherapy regimens like CHOP and ACVBP significantly improves treatment outcomes for lymphoma patients, allowing for fewer cycles of treatment without compromising efficacy.

Using positron emission tomography (PET) scans early in treatment can help predict long-term outcomes, enabling personalized treatment plans based on individual patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current approaches to the treatment of non-Hodgkin's lymphoma. Gisselbrecht, C.[2021]

In a pooled analysis of 150 patients with HIV-associated aggressive B-cell non-Hodgkin lymphoma, those treated with R-EPOCH showed significantly better event-free survival (EFS) and overall survival (OS) compared to those receiving R-CHOP, particularly in patients with a CD4 count ≥100/μL.

Patients with CD4 counts <50/μL experienced a much higher rate of treatment-related deaths (37% vs 6%), indicating that lower immune function increases the risk of lethal toxicity during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma. Barta, SK., Lee, JY., Kaplan, LD., et al.[2022]

In a study of 40 patients with low-grade or follicular B-cell non-Hodgkin's lymphoma, the combination of Rituxan (Rituximab) and CHOP chemotherapy resulted in a high overall response rate of 95%, with 55% achieving complete remission.

The combination therapy showed promising safety, with common side effects being manageable, and it also indicated potential for clearing minimal residual disease, as evidenced by the conversion of the bcl-2 translocation from positive to negative in several patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. Czuczman, MS., Grillo-López, AJ., White, CA., et al.[2022]

In a study of 60 previously untreated patients with intermediate- or high-grade non-Hodgkin's lymphomas, the combination chemotherapy regimen CEOP-B/VIMB achieved a high complete remission rate of 77% and a 48-month overall survival rate of 70%.

The treatment demonstrated mild toxicity, making it a favorable option compared to third-generation regimens, while patient outcomes were significantly influenced by factors such as serum LDH levels and performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CEOP-B alternated with VIMB in intermediate-grade and high-grade non-Hodgkin's lymphoma: a pilot study. De Lena, M., Ditonno, P., Lorusso, V., et al.[2017]

In a study of 91 people living with HIV and Burkitt lymphoma, adding rituximab to CODOX-M/IVAC chemotherapy did not increase severe treatment-related toxicities, indicating it is a safe option for this population.

The addition of rituximab significantly improved both overall survival (72% vs. 55%) and progression-free survival (81% vs. 55%) compared to chemotherapy alone, suggesting it enhances treatment efficacy without added risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding rituximab to CODOX-M/IVAC chemotherapy in the treatment of HIV-associated Burkitt lymphoma is safe when used with concurrent combination antiretroviral therapy. Alwan, F., He, A., Montoto, S., et al.[2022]

In a study of 30 patients with refractory or relapsing non-Hodgkin's lymphoma, the DVIP treatment led to a 33% complete response rate and a 30% partial response rate, with responses lasting from 2.5 to over 24 months.

While DVIP treatment caused significant myelosuppression, it was considered safe as there were no drug-related deaths, indicating it is an effective salvage therapy for aggressive forms of NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage therapy for non-Hodgkin's lymphoma with a combination of dexamethasone, etoposide, ifosfamide, and cisplatin. Haim, N., Rosenblatt, E., Wollner, M., et al.[2019]

Rituximab, a chimeric anti-CD20 monoclonal antibody, has shown to induce responses in nearly 50% of patients with relapsed follicular/low-grade non-Hodgkin's lymphoma, with complete remissions occurring in 6% of cases, highlighting its efficacy in treating this type of cancer.

The drug is generally well tolerated, with common side effects being mild to moderate fevers and chills, and it is also effective against various other B-cell malignancies, suggesting its potential for broader applications in both cancer treatment and autoimmune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: clinical development and future directions. Cheson, BD.[2019]

The combination of bendamustine and rituximab showed promising therapeutic efficacy in treating lymphoproliferative diseases, achieving an overall response rate of 65% in chronic lymphocytic leukemia (CLL) and 96% in indolent lymphoma among 71 patients studied.

However, the treatment was associated with significant hematotoxicity, with severe neutropenia and thrombocytopenia occurring in 33% and 18% of patients, respectively, and a notable risk of severe infections in aggressive lymphoma and CLL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Routine use of bendamustine and rituximab combination therapy in consecutive patients with lymphoproliferative diseases: a survey from Tyrolean hospitals. Waldthaler, C., Stauder, R., Schnallinger, M., et al.[2021]

References

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

Rituximab: a new therapeutic monoclonal antibody for non-Hodgkin's lymphoma. [2022]

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

Is there any role for transplantation in the rituximab era for diffuse large B-cell lymphoma? [2022]

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

Biological therapy doublets: pairing rituximab with interferon, lenalidomide, and other biological agents in patients with follicular lymphoma. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Treatment of refractory and relapsed non-Hodgkin's lymphoma with ifosfamide, methotrexate and etoposide. [2019]

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

Current approaches to the treatment of non-Hodgkin's lymphoma. [2021]

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

Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma. [2022]

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

Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. [2022]

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

CEOP-B alternated with VIMB in intermediate-grade and high-grade non-Hodgkin's lymphoma: a pilot study. [2017]

9. England pubmed.ncbi.nlm.nih.gov

Adding rituximab to CODOX-M/IVAC chemotherapy in the treatment of HIV-associated Burkitt lymphoma is safe when used with concurrent combination antiretroviral therapy. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Salvage therapy for non-Hodgkin's lymphoma with a combination of dexamethasone, etoposide, ifosfamide, and cisplatin. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Rituximab: clinical development and future directions. [2019]

12. Austria pubmed.ncbi.nlm.nih.gov

Routine use of bendamustine and rituximab combination therapy in consecutive patients with lymphoproliferative diseases: a survey from Tyrolean hospitals. [2021]