Combination Therapy for Lymphoma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment for individuals with diffuse large B-cell lymphoma, a type of cancer that has returned or is not responding to treatment. The study examines a combination of an immune-targeting drug and several chemotherapy drugs, including Carboplatin, Etoposide, Ifosfamide, Polatuzumab Vedotin, and Rituximab, to determine if they work better together to kill cancer cells. It targets those who have tried other treatments without success and are seeking another approach. For those with lymphoma that has relapsed or is resistant to initial treatments, this trial might be suitable. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants, offering a chance to contribute to important findings.

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.

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

Research has shown that the drug combination PolaR-ICE, which includes polatuzumab vedotin, rituximab, ifosfamide, carboplatin, and etoposide, is being tested for safety in patients with relapsed or hard-to-treat diffuse large B-cell lymphoma. Previous studies found that polatuzumab vedotin can directly target cancer cells, potentially reducing some side effects compared to other treatments.

Rituximab, one of the drugs in this combination, is widely used in other lymphoma treatments and is known to be safe. The chemotherapy drugs ifosfamide, carboplatin, and etoposide are also well-established, though they can cause side effects like nausea, tiredness, and low blood counts.

In studies with similar drug combinations, some side effects have been reported, including infections due to a weakened immune system and blood-related issues, which are common with chemotherapy. However, serious side effects were less common. These findings suggest that the treatment is generally well-tolerated, but like all treatments, it carries some risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard lymphoma treatments, which typically involve chemotherapy and targeted therapies, the PolaR-ICE combination therapy introduces a novel approach by incorporating polatuzumab vedotin. This drug is an antibody-drug conjugate that specifically targets and delivers a potent chemotherapy agent directly to lymphoma cells, potentially enhancing efficacy while reducing harm to normal cells. Researchers are excited because this targeted delivery method could improve treatment outcomes and minimize side effects compared to traditional chemotherapy regimens.

What evidence suggests that this trial's treatments could be effective for diffuse large B-cell lymphoma?

In this trial, participants will receive the combination therapy PolaR-ICE, which includes polatuzumab vedotin, rituximab, ifosfamide, carboplatin, and etoposide. Studies have shown that this combination improves outcomes for patients with diffuse large B-cell lymphoma that has returned or is unresponsive to treatment. Research indicates that this therapy significantly extends the time patients can go without their cancer worsening or causing complications. Polatuzumab vedotin targets cancer cells and delivers a toxic substance to kill them. Rituximab prevents cancer cells from growing and spreading. The chemotherapy drugs ifosfamide, carboplatin, and etoposide stop cancer cells from dividing or spreading. Overall, evidence suggests that PolaR-ICE could be an effective treatment option for these patients. ^{1 3 4 5 6}

Who Is on the Research Team?

Alex F Herrera

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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 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 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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04665765?term=AREA%5BConditionSearch%5D(%22Diffuse%20Large%20B-Cell%20Lymphoma%22)%20AND%20AREA%5BInterventionSearch%5D(%22Ifosfamide%22)&rank=8&tab=results

Study Results | Polatuzumab Vedotin, Rituximab, Ifosfamide, ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

2. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/1065/491023/Polatuzumab-Vedotin-Combined-with-R-ICE-PolaR-ICE

Polatuzumab Vedotin Combined with R-ICE (PolaR-ICE) As ... We evaluated the safety and efficacy of Pola combined with rituximab, ifosfamide, carboplatin, and etoposide (RICE) as second-line tx in RR ...

3. clinicaltrials.eu clinicaltrials.eu/trial/study-comparing-polatuzumab-vedotin-with-rituximab-ifosfamide-carboplatin-and-etoposide-for-adults-with-relapsed-or-refractory-diffuse-large-b-cell-lymphoma/

Study Comparing Polatuzumab Vedotin with Rituximab ... This study investigates the use of Polatuzumab Vedotin in combination with Rituximab, Ifosfamide, Carboplatin, and Etoposide for treating ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04182204

NCT04182204 | A Study to Evaluate the Safety and ... The safety run-in stage (Stage 1) will assess the safety of polatuzumab vedotin plus rituximab, gemcitabine and oxaliplatin (Pola-R-GemOx) in 10 participants.

5. isrctn.com isrctn.com/ISRCTN13438605

A trial looking at the effectiveness of combining standard R ... Combining polatuzumab vedotin with rituximab, ifosfamide, carboplatin and etoposide chemotherapy (Pola-R-ICE) improves event-free survival in patients with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9894203/

Polatuzumab Vedotin for the Front-Line Treatment of Diffuse ... This study randomized newly diagnosed DLBCL patients to receive polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin ...