Chemotherapy + Carfilzomib for Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Roswell Park Cancer Institute

Must not be taking: High-dose corticosteroids

Disqualifiers: Non-Hodgkin lymphoma, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 9-12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments to determine the best dose and assess their effectiveness for individuals with a specific type of lymphoma (a blood cancer) that has returned or not responded to previous treatments. The study examines the addition of carfilzomib, a drug that may block cancer growth, to a mix of other cancer-fighting drugs like rituximab and chemotherapy agents, including carboplatin, etoposide, and ifosfamide. The goal is to stop cancer cells from growing or spreading more effectively. Individuals with diffuse large B-cell lymphoma that has recurred or is unresponsive to treatment, and who have already tried at least one prior rituximab-based treatment, might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have had chemotherapy within 3 weeks before the first scheduled study treatment or if you are on high-dose systemic corticosteroids.

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

A previous study raised safety concerns about carfilzomib, particularly regarding kidney problems. Acute kidney failure occurred more frequently in patients with advanced multiple myeloma treated with carfilzomib. Patients should be closely monitored for these side effects.

Rituximab is generally well-tolerated, though some patients have experienced reactions like fever or chills during their first treatment session. Observation during and after the infusion is important.

Etoposide has been well-tolerated in older patients with aggressive lymphomas, including non-Hodgkin lymphoma, suggesting it could be safe for wider use. However, monitoring is always recommended for any treatment.

Carboplatin can lower white blood cell counts, increasing the risk of infection. Regular blood tests and monitoring should manage this side effect.

Ifosfamide is used to treat various cancers, including lymphoma. It has been part of effective treatment plans but requires careful monitoring for side effects.

This early-phase trial focuses mainly on safety. Researchers aim to identify any adverse effects and determine the safest dose for future studies. The treatment's full safety profile is still being developed, so participants will be closely monitored for any side effects during the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this lymphoma treatment because it combines carfilzomib with traditional chemotherapy drugs like carboplatin and ifosfamide. Carfilzomib is a proteasome inhibitor that works differently from other treatments, targeting protein degradation pathways in cancer cells, which can lead to their death. Unlike standard treatments that mainly rely on chemotherapy alone, this combination aims to enhance the effectiveness against lymphoma. By integrating carfilzomib, the treatment could potentially overcome resistance seen in some lymphoma cases, offering new hope for patients.

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

In this trial, participants will receive a combination of treatments, including carfilzomib, rituximab, and chemotherapy. Previous studies have shown that carfilzomib effectively treats certain cancers by blocking enzymes that cancer cells need to grow, resulting in a high overall response rate of about 68.8%. Rituximab, a type of targeted therapy, has proven very effective for B-cell non-Hodgkin's lymphoma, with a response rate of 92%. Etoposide significantly improved outcomes for lymphoma patients. Carboplatin, often used with other drugs, achieved response rates between 65% and 85% in some cases. Lastly, ifosfamide effectively treated lymphomas, with around 70% of patients experiencing at least a partial response. Together, these treatments aim to improve outcomes for patients with diffuse large B-cell lymphoma in this trial. ^{3 6 7 8 9}

Who Is on the Research Team?

Francisco J. Hernandez-ILizaliturri

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with stage I-IV diffuse large B-cell lymphoma that has relapsed or is refractory. Participants must have had at least one prior rituximab-based treatment, measurable disease, and adequate organ function. They should not be pregnant/breastfeeding, HIV positive, have certain other cancers or severe medical conditions.

Inclusion Criteria

I have a tumor that can be measured and is at least 2.25 cm^2 in size.

My lymphoma has returned or didn't respond to treatment and tests positive for CD20.

My kidney function is normal or meets the trial's requirements.

Exclusion Criteria

I have active brain or spinal cord lymphoma but am still eligible if a specific test shows DLBCL at registration.

I have tested positive for hepatitis B surface antigen or have hepatitis B core antibodies with a negative DNA test.

I have symptoms from cancer spreading to my brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive carfilzomib, rituximab, etoposide, carboplatin, and ifosfamide in 21-28 day cycles for up to 3 courses

9-12 weeks

Multiple visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 4 months for 1 year, every 6 months for 2 years, then annually for 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Carfilzomib
• Etoposide
• Ifosfamide
• Rituximab

Trial Overview The study tests the safety and optimal dose of carfilzomib combined with rituximab, ifosfamide, carboplatin, and etoposide in treating relapsed/refractory diffuse large B-cell lymphoma to see how well it works compared to standard treatments.

How Is the Trial Designed?

Group I: Treatment (carfilzomib, rituximab, chemotherapy) Experimental Treatment 7 Interventions

Patients receive carfilzomib IV over 10-30 minutes on days 1, 2, 8, and 9; rituximab IV over 3-8 hours on day 3; etoposide IV over 1 hour on days 4-6; carboplatin IV over 1 hour on day 5; and ifosfamide IV over 24 hours on day 5. Treatment repeats every 21-28 days for up to 3 courses 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?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

In a phase II study involving 46 adults with refractory and relapsed acute leukemia, carboplatin administered via continuous infusion led to a 17% complete remission rate, indicating its effectiveness as a treatment option for this patient population.

While carboplatin showed some nonhematologic toxicity, such as mild gastrointestinal issues and manageable ototoxicity, the major concern was prolonged myelosuppression, with infections being the leading cause of death among participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose carboplatin in the treatment of hematologic malignancies. Vogler, WR.[2018]

In a Phase II study involving 46 patients with metastatic breast cancer, the combination of carboplatin and etoposide showed a 42% objective response rate in patients who had not received prior chemotherapy, indicating its potential effectiveness as a treatment option.

However, the combination was ineffective in patients who had previously undergone chemotherapy for metastatic cancer, suggesting it may not be suitable for salvage therapy in those cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of carboplatin and etoposide in metastatic breast cancer. Crown, J., Hakes, T., Reichman, B., et al.[2019]

In a Phase I trial involving 18 patients with advanced non-small cell lung cancer (NSCLC), the combination of carboplatin and cisplatin was found to have a manageable toxicity profile, with thrombocytopenia being the main dose-limiting effect and a maximum tolerated dose of 350 mg/m2 for carboplatin.

In a subsequent Phase II trial with 13 patients, using a safer carboplatin dose of 300 mg/m2, 38.5% of patients showed a partial response to the treatment, indicating that this combination chemotherapy may be effective for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined carboplatin and cisplatin therapy in patients with advanced non-small cell lung cancer. Nakanishi, R., Kume, T., Mitsudomi, T., et al.[2019]

In a phase II trial involving 55 patients with limited-stage small cell lung cancer, the combination of paclitaxel, carboplatin, and etoposide showed promising efficacy, with 37.1% achieving a complete response and 51.4% a partial response.

The treatment was associated with moderate toxicity, primarily hematologic, but no life-threatening complications were reported, indicating that the regimen is tolerable for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel, carboplatin, and oral etoposide: a phase II trial in limited-stage small cell lung cancer. Gatzemeier, U., Jagos, U., Kaukel, E., et al.[2015]

Carboplatin/etoposide is an effective treatment for small cell lung cancer, showing results comparable to the traditional cisplatin/etoposide combination, although it has not been directly compared in a randomized study.

This combination has a better safety profile, particularly in elderly patients, and lacks significant nonhematologic side effects, making it suitable for further studies involving dose escalation and bone marrow transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin/etoposide in small cell lung cancer. Bishop, JF.[2018]

Citations

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Efficacy and Safety of Gemcitabine (G), Carboplatin (C ... Such strategies have yielded response rates of 65–85% and complete response rates of 20–30% in younger, transplant-eligible patients with diffuse large B-cell ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17675395/

Long-term outcomes with concurrent carboplatin, paclitaxel ... With a median follow-up of 69 months for surviving patients, the 5-year progression-free survival was 36% and the 5-year overall survival was 35%. Two of the 18 ...

3. healthtree.org healthtree.org/anaplastic-large-cell-lymphoma/medications/carboplatin

Carboplatin - Chemotherapy Agents Its effects are similar to those of cisplatin, another platinum-based chemotherapy, but carboplatin tends to have fewer kidney and nerve side effects.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925006288

Survival outcomes with carboplatin versus cisplatin and the ... The aim of this study was to compare OS between patients treated with carboplatin-etoposide and cisplatin-etoposide in both LS-SCLC and ES-SCLC ...

5. cancertherapyadvisor.com cancertherapyadvisor.com/news/carboplatin-ovarian-cancer-monotherapy-proves-inferior-treatment/

Carboplatin Monotherapy Proves Inferior to Standard ... Patients who received single-agent carboplatin had the worst progression-free survival (PFS). The median PFS was 4.8 months with single-agent ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35429391/

Safety and Tolerability of Carboplatin and Paclitaxel in Cancer ... We performed a pilot trial to evaluate the safety of full-dose PCb in people living with human immunodeficiency virus and cancer.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12206876/

Real-world safety of carboplatin in non-small cell lung cancer This study aims to systematically assess carboplatin-related AEs and explore demographic factors that may influence risk.

8. mayoclinic.org mayoclinic.org/drugs-supplements/carboplatin-intravenous-route/description/drg-20062578

Carboplatin (intravenous route) - Side effects & uses Carboplatin can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of ...

9. adcreview.com adcreview.com/wp-content/uploads/2022/03/PARAPLATIN%C2%AE-carboplatin-BMS.pdf

PARAPLATIN Label Carboplatin, like cisplatin, produces predominantly interstrand DNA cross-links rather than DNA-protein cross-links. This effect is apparently cell-cycle ...