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

29 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination of chemotherapy and Carfilzomib for treating lymphoma?

Research shows that adding Carfilzomib to a chemotherapy regimen including rituximab, ifosfamide, carboplatin, and etoposide (C-R-ICE) improves outcomes in patients with relapsed or refractory diffuse large B-cell lymphoma, especially in those with the non-germinal center B-cell-like subtype, with a high overall response rate and longer survival times. ^{1 2 3 4 5}

Is the combination of chemotherapy drugs including carboplatin, etoposide, and others generally safe for humans?

The combination of carboplatin and etoposide has been studied in various cancers and is generally well-tolerated, with the main side effects being related to blood cell production (myelosuppression). Non-blood-related side effects are usually mild, such as nausea and vomiting, and serious complications are rare. ^{6 7 8 9 10}

What makes the chemotherapy + carfilzomib treatment unique for lymphoma?

This treatment is unique because it combines carfilzomib, a drug that can overcome resistance to rituximab-chemotherapy, with a regimen known as R-ICE (rituximab, ifosfamide, carboplatin, and etoposide), improving outcomes for patients with relapsed or refractory diffuse large B-cell lymphoma, especially those with the non-germinal center B-cell-like subtype. ^{1 2 3 4 5}

What is the purpose of this trial?

This phase I/Ib trial studies the side effects and best dose of carfilzomib when given together with rituximab, ifosfamide, carboplatin, and etoposide and to see how well it works in treating patients with stage I-IV diffuse large B-cell lymphoma that has returned (relapsed) or that has not responded to treatment (refractory). Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as ifosfamide, carboplatin, and etoposide, also work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving carfilzomib with rituximab, ifosfamide, carboplatin, and etoposide may be a better treatment for diffuse large B-cell lymphoma.

Research Team

Francisco J. Hernandez-ILizaliturri

Principal Investigator

Roswell Park Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

References

1. France pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics and Pharmacodynamics of Carfilzomib in Combination with Rituximab, Ifosfamide, Carboplatin, and Etoposide in Adult Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma. [2023]

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

Carfilzomib combined with rituximab, ifosfamide, carboplatin, and etoposide for relapsed or refractory DLBCL. [2023]

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

Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with non-Hodgkin's lymphoma. [2017]

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

Phase I and II study of high-dose ifosfamide, carboplatin, and etoposide with autologous bone marrow rescue in lymphomas and solid tumors. [2017]

5. England pubmed.ncbi.nlm.nih.gov

ICE (ifosfamide, carboplatin, etoposide) as second-line chemotherapy in relapsed or primary progressive aggressive lymphoma--the Nordic Lymphoma Group experience. [2014]

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

Paclitaxel, carboplatin, and oral etoposide: a phase II trial in limited-stage small cell lung cancer. [2015]

7. Switzerland pubmed.ncbi.nlm.nih.gov

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

8. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Combined carboplatin and cisplatin therapy in patients with advanced non-small cell lung cancer. [2019]

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

Phase II trial of carboplatin and etoposide in metastatic breast cancer. [2019]