What side effects are associated with this type of intervention?

Pralatrexate, an enzyme inhibitor, commonly causes side effects such as mucositis, thrombocytopenia, neutropenia, and fatigue. Pembrolizumab, an immune checkpoint inhibitor, can lead to immune-related adverse events including rash, diarrhea, hypothyroidism, and pruritus. Severe side effects may include liver toxicity and infusion reactions. Combining these treatments may enhance efficacy but also increases the risk of compounded side effects.

What prior FDA approvals exist?

For the treatment of Peripheral T-Cell Lymphoma (PTCL), the FDA has approved pralatrexate, an enzyme inhibitor that targets folate metabolism, and pembrolizumab, an immune checkpoint inhibitor that enhances the immune system's ability to attack cancer cells. Other similar FDA-approved treatments include romidepsin and belinostat, both of which are histone deacetylase inhibitors that affect gene expression and protein function in cancer cells. These treatments offer different mechanisms of action, providing multiple therapeutic options for managing PTCL.

What other types of research exist?

Promising novel alternatives for PTCL treatment in 2024 include: 1) Bispecific antibodies such as epcoritamab, mosunetuzumab, and glofitamab, which engage T-cells to target cancer cells. 2) Anti-CD19 antibody drug tafasitamab combined with lenalidomide, which targets CD19 on cancer cells and modulates the immune system. 3) CD19 antibody drug conjugate loncastuximab tesirine, which delivers cytotoxic agents directly to cancer cells. 4) Oral selective inhibitor of nuclear export selinexor, which disrupts cancer cell survival mechanisms.

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PD-1 Inhibitor

Pembrolizumab + Pralatrexate for Peripheral T-Cell Lymphoma

Phase 1 & 2

Waitlist Available

Led By Alex F Herrera

Research Sponsored by City of Hope Medical Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have a histologically confirmed diagnosis of mature peripheral T-cell or natural killer (NK)-cell lymphoma according to the World Health Organization (WHO) classification, with hematopathology review at the participating institution

If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants

Must not have

Patients with adult T-cell leukemia/lymphoma

Patients who received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent without having had evidence of objective response

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 43 months after the initial study treatment.

Awards & highlights

All Individual Drugs Already Approved

Approved for 5 Other Conditions

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include reactions related to immune system activation such as inflammation in various organs, infusion-related reactions from the drug entering the body, fatigue, liver enzyme changes, digestive issues like nausea or mouth sores from chemotherapy, and increased risk of infection.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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My blood clotting time is within the target range for my anticoagulant therapy.

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My blood clotting time is near normal and I'm not on blood thinners.

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I have a tumor that is larger than 1.5cm, confirmed by CT or PET scan.

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I am fully active or restricted in physically strenuous activity but can do light work.

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My blood clotting time is within normal limits.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have adult T-cell leukemia/lymphoma.

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

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I have active hepatitis B or C.

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I have had tuberculosis in the past.

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I have an autoimmune disease treated with medication in the last 2 years.

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I have been diagnosed with HIV.

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I have an infection that needs treatment with medication.

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I haven't had cancer drug therapy or major surgery in the last 3 weeks.

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I had a stem cell transplant from a donor within the last 5 years.

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I had a stem cell transplant using my own cells within the last 2 months.

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I took pralatrexate before but it didn't shrink my cancer.

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I haven't taken any experimental cancer drugs or antibodies in the last 21 days.

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I haven't had cancer treatment or recovered from its side effects in the last 14 days.

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I have been diagnosed with an immune system disorder.

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I have severe limitations due to heart failure.

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My lymphoma has spread to my brain or spinal cord.

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I am not pregnant or breastfeeding.

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I have had pneumonitis treated with steroids or have it now.

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I have another cancer that is getting worse or needs treatment.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 43 months after the initial study treatment.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 43 months after the initial study treatment.

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 43 months after the initial study treatment. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of Participants Who Had Dose Limiting Toxicities

Number of Participants Who Had Overall Response

Secondary study objectives

Number of Participants Who Had Complete Response (CR)

Number of Participants With Grade 3 4 5 Adverse Events

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Sepsis

Pneumonia aspiration

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Clostridium difficile colitis

Systemic infection

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Placebo + CRT Followed by Placebo

Pembrolizumab + CRT Followed by Pembrolizumab

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (pralatrexate and pembrolizumab)Experimental Treatment2 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

FDA approved

Pralatrexate

FDA approved

0 / 25Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Peripheral T-Cell Lymphoma (PTCL) include pralatrexate and pembrolizumab. Pralatrexate inhibits dihydrofolate reductase, an enzyme essential for DNA synthesis, thereby preventing cancer cell growth. Pembrolizumab is an immune checkpoint inhibitor that blocks the PD-1 receptor on T-cells, enhancing the immune system's ability to attack cancer cells. This dual approach of directly targeting cancer cell proliferation and boosting the body's immune response is crucial for effectively managing PTCL.