Pembrolizumab + Pralatrexate for Peripheral T-Cell Lymphoma

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

13 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies the combination of pralatrexate and pembrolizumab in patients with peripheral T-cell lymphomas that have returned or not responded to treatment. Pralatrexate blocks cancer cell growth, while pembrolizumab boosts the immune system to attack cancer cells. The goal is to find the best dose and see how well this combination works.

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.

What data supports the effectiveness of the drug Pralatrexate for treating peripheral T-cell lymphoma?

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 10.1 months in patients with relapsed or refractory disease. It was the first drug approved by the FDA for this condition. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and Pralatrexate safe for humans?

Pralatrexate has been approved for treating certain types of lymphoma, but it can cause mouth sores (mucositis) as a side effect, which can be managed with vitamin supplements. There is no specific safety data available for the combination of Pembrolizumab and Pralatrexate. ^{1 2 6 7 8}

What makes the drug combination of Pembrolizumab and Pralatrexate unique for treating peripheral T-cell lymphoma?

This treatment combines Pembrolizumab, an immune system booster, with Pralatrexate, the first FDA-approved drug specifically for relapsed or refractory peripheral T-cell lymphoma, offering a novel approach by potentially enhancing the immune response while directly targeting cancer cells. ^{2 3 4 5 9}

Research Team

Alex F Herrera

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

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

Folotyn (pralatrexate injection) for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma: U.S. Food and Drug Administration drug approval summary. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Critical appraisal of pralatrexate in the management of difficult-to-treat peripheral T cell lymphoma. [2021]

3. France pubmed.ncbi.nlm.nih.gov

Pralatrexate in Chinese Patients with Relapsed or Refractory Peripheral T-cell Lymphoma: A Single-arm, Multicenter Study. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Evaluation of the pharmacokinetics, preclinical and clinical efficacy of pralatrexate for the treatment of T-cell lymphoma. [2013]

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

Pralatrexate injection for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Phase 1 study evaluating the safety and pharmacokinetics of pralatrexate in relapsed/refractory advanced solid tumors and lymphoma patients with mild, moderate, and severe renal impairment. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Pralatrexate for refractory mycosis fungoides in two Japanese patients. [2021]

8. Italy pubmed.ncbi.nlm.nih.gov

Pralatrexate, a new hope for aggressive T-cell lymphomas? [2022]

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

Pralatrexate induced durable response in a relapsed/refractory peripheral T-cell lymphoma patient with a history of autologous stem cell transplantation: Case report of a patient followed-up over 3 years under pralatrexate treatment. [2022]