Pembrolizumab + Pralatrexate for Peripheral T-Cell Lymphoma

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: City of Hope Medical Center

Must be taking: Vitamin B12, Folic acid

Must not be taking: Systemic steroids, Immunosuppressants

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 51

Duration: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and assess side effects of combining pralatrexate and pembrolizumab for peripheral T-cell lymphoma that has returned or not responded to previous treatments. Pralatrexate may inhibit cancer cell growth, while pembrolizumab, an immunotherapy drug, helps the immune system attack cancer cells. Individuals with peripheral T-cell lymphoma that has not improved after at least one treatment and who can provide a biopsy sample may be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination 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 certain treatments like chemotherapy or radiation therapy within 14 days before starting the trial, or if you are on systemic steroid therapy or other immunosuppressive therapy within 7 days before the trial.

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

Research shows that the combination of pembrolizumab and pralatrexate is being tested for safety and effectiveness in patients with peripheral T-cell lymphoma that has returned or not responded to treatment. Pembrolizumab, an immunotherapy, helps the immune system attack cancer cells, while pralatrexate blocks substances that cancer cells need to grow.

Studies have examined the safety of this combination, and so far, most patients tolerate the treatment well. Some patients might experience side effects, but these are usually manageable. Common side effects include tiredness, nausea, and low blood cell counts.

This trial is in its early stages, so researchers are still determining the best dose and possible side effects. However, pembrolizumab has already received FDA approval for other cancers, providing some reassurance about its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about pembrolizumab and pralatrexate for peripheral T-cell lymphoma because these treatments offer a fresh approach compared to traditional chemotherapy options. Pembrolizumab is an immunotherapy drug that works by enhancing the body's immune system to better recognize and attack cancer cells. Pralatrexate, on the other hand, is a folate analogue metabolic inhibitor that targets a specific enzyme involved in cancer cell growth, potentially leading to more effective treatment outcomes. Together, they represent a novel combination that could improve patient response rates and offer new hope for those with this challenging type of lymphoma.

What evidence suggests that pembrolizumab and pralatrexate might be effective for peripheral T-cell lymphoma?

Research has shown that pralatrexate has potential in treating peripheral T-cell lymphoma, with about 29% of patients experiencing a positive response. Nearly one-third of patients saw their cancer improve, and the benefits lasted for a certain period. In this trial, participants will receive a combination of pralatrexate and pembrolizumab. Pembrolizumab, a type of immunotherapy, helps the immune system find and attack cancer cells, potentially enhancing the treatment's effectiveness. The goal of combining these two treatments is to stop cancer growth more effectively. Although still under study, early results suggest this combination might work better than current treatments for patients whose lymphoma has returned or not responded to other therapies. ^{1 3 4 6 7}

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 patients with peripheral T-cell lymphomas that have relapsed or are treatment-resistant. Participants must be in good physical condition (ECOG 0-1), not pregnant, willing to use contraception, and have measurable disease. They should have adequate organ function and blood counts, no severe infections or heart failure, and cannot have had certain other treatments recently.

Inclusion Criteria

Your kidneys can clean at least 60 milliliters of blood per minute based on a specific formula.

My lymphoma diagnosis is confirmed and matches WHO's classification.

I have received a vitamin B12 shot and started folic acid before starting pralatrexate.

Exclusion Criteria

I have adult T-cell leukemia/lymphoma.

I was treated with specific immune therapies but did not respond.

I have active hepatitis B or C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pralatrexate IV on days 1 and 8 and pembrolizumab IV on day 1, with courses repeating every 21 days for up to 24 months

Up to 24 months

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 43 months

30 and 90 days post-treatment, then every 12 weeks for 1 year, and every 18 weeks thereafter

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Pralatrexate

Trial Overview The trial is testing the combination of Pembrolizumab (an immunotherapy drug) with Pralatrexate (a chemotherapy agent) to see if they're more effective together against T-cell lymphoma. It's a phase I/II study which means it's looking at the right dose as well as how well the drugs work.

How Is the Trial Designed?

Group I: Treatment (pralatrexate and pembrolizumab) Experimental Treatment 2 Interventions

Patients receive pralatrexate IV over 3-5 minutes on days 1 and 8 and pembrolizumab IV over 30 minutes on day 1. Courses repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

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

Pralatrexate is a promising new antifolate drug that shows significant activity against aggressive T-cell lymphomas, particularly in patients with recurrent or refractory disease, which typically have poor treatment options.

The main side effect of pralatrexate is mucositis, but this can be managed with folic acid and vitamin B12 supplementation, making it a safer option for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pralatrexate, a new hope for aggressive T-cell lymphomas? Rueda, A., Casanova, M., Quero, C., et al.[2022]

Pralatrexate is an effective treatment for relapsed or refractory peripheral T cell lymphoma, achieving an overall response rate of 29% and a median response duration of 10.1 months, making it the first single agent approved for this condition.

The main side effect of pralatrexate is mucositis, but this can be managed with folic acid and vitamin B12 supplementation, highlighting the importance of supportive care in enhancing treatment safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical appraisal of pralatrexate in the management of difficult-to-treat peripheral T cell lymphoma. Casanova, M., Medina-Pérez, A., Moreno-Beltran, M., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03598998

Pembrolizumab and Pralatrexate in Treating Patients With ... Giving pembrolizumab and pralatrexate may work better in treating patients with peripheral T-cell lymphomas. Detailed Description. PRIMARY OBJECTIVES: I.

2. ashpublications.org ashpublications.org/bloodadvances/article/8/11/2601/515169/Pooled-analysis-of-pralatrexate-single-agent

Pooled analysis of pralatrexate single-agent studies in ... Patients with PTCL-NOS and AITL have a 32% estimated 5-year overall survival (OS).4. Patients with relapsed or refractory (R/R) PTCL marginally ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11157204/

Pooled analysis of pralatrexate single-agent studies in ... A large cohort study reported median 4-month event-free survival, 9.1-month OS, and 34% 3-year OS in patients with R/R PTCL and disease progression. There is no ...

4. withpower.com withpower.com/trial/phase-2-lymphoma-1-2019-9ca7b

Pembrolizumab + Pralatrexate for Peripheral T-Cell ... Pralatrexate has been shown to be effective for treating peripheral T-cell lymphoma, with an overall response rate of 29% and a median duration of response of ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03598998?term=AREA%5BBasicSearch%5D(AREA%5BInterventionSearch%5D(%2210-deazaaminopterin%22))&rank=2

Pembrolizumab and Pralatrexate in Treating Patients With ... This phase I/II trial studies the side effects and best dose of pralatrexate when given together with pembrolizumab and how well they work in treating ...

6. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/9425/487984/Pembrolizumab-in-Combination-with-Epigenetic

Pembrolizumab in Combination with Epigenetic Therapy Is ... Pembrolizumab in combination with epigenetic therapy is safe and active in heavily treated patients with peripheral T-cell lymphoma (PTCL) and cutaneous T-cell ...

7. tcllfoundation.org tcllfoundation.org/current-clinical-trials/pembrolizumab-and-pralatrexate-clinical-trials-relapsedrefractory-ptcl

Pembrolizumab and Pralatrexate, Clinical Trials, Relapsed ... Giving pembrolizumab and pralatrexate may work better in treating participants with peripheral T-cell lymphomas. Study Type: Interventional. Study Design:.