Pembrolizumab and Pralatrexate in Treating Patients With Relapsed or Refractory Peripheral T-Cell Lymphomas
A Phase 1/2 Study of Pembrolizumab Plus Pralatrexate for Treatment of Relapsed or Refractory Peripheral T-Cell Lymphomas
2 other identifiers
interventional
13
1 country
3
Brief Summary
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 patients with peripheral T-cell lymphomas that has come back after a period of improvement or has not responded to treatment. Pralatrexate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab and pralatrexate may work better in treating patients with peripheral T-cell lymphomas.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Feb 2019
Longer than P75 for phase_1
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 16, 2018
CompletedFirst Posted
Study publicly available on registry
July 26, 2018
CompletedStudy Start
First participant enrolled
February 4, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 3, 2023
CompletedResults Posted
Study results publicly available
August 27, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
February 26, 2026
CompletedJune 26, 2025
June 1, 2025
4.2 years
July 16, 2018
July 2, 2024
June 18, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Number of Participants Who Had Dose Limiting Toxicities
Dose limiting toxicities (DLT) were defined as one of the AEs in Protocol Section 5.5 that at least possibly related to study treatment. The DLT observation period was 2 cycles of therapy, from the start of Cycle 1 through the start of Cycle 3. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).
From the start of Cycle 1 through the start of Cycle 3 (approximately 42 days)
Number of Participants Who Had Overall Response
Number of participants who had a documented complete response (CR) or partial response (PR) at any time during study treatment. Disease response/progression by PET-CT or CT was evaluated using 2014 Lugano Classification.
Up to 43 months after the initial study treatment.
Secondary Outcomes (2)
Number of Participants Who Had Complete Response (CR)
Up to 43 months after the initial study treatment.
Number of Participants With Grade 3 4 5 Adverse Events
From the start time of the initial treatment assessed through 8 treatment cycles (21 days per cycle) up to 90 days from last dose (approximately 9 months).
Study Arms (1)
Treatment (pralatrexate and pembrolizumab)
EXPERIMENTALPatients 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.
Interventions
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Documented willingness and ability to sign an informed consent of the participant and/or legally authorized representative.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- 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. Eligible histologies are:
- Peripheral T-cell lymphoma, not otherwise specified
- Anaplastic large cell lymphoma, ALK-negative
- Anaplastic large cell lymphoma, ALK-positive
- Angioimmunoblastic T-cell lymphoma
- Nodal peripheral T-cell lymphoma with TFH phenotype
- Follicular T-cell lymphoma
- Indolent T-cell lymphoproliferative disorder of the gastrointestinal (GI) tract
- Extranodal NK-/T-cell lymphoma
- Enteropathy-associated T cell lymphoma
- Monomorphic epitheliotropic intestinal T-cell lymphoma
- Hepatosplenic T-cell lymphoma
- Subcutaneous panniculitis-like T-cell lymphoma
- +24 more criteria
You may not qualify if:
- Patients with adult T-cell leukemia/lymphoma
- Prior allogeneic hematopoietic stem cell transplantation within the last 5 years.
- Prior autologous hematopoietic stem cell transplant within the last 60 days.
- 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.
- Patients who received prior therapy with pralatrexate without having had evidence of objective response.
- Investigational agent or anti-cancer monoclonal antibody (mAb) within 21 days prior to day 1 of therapy or who has not recovered (i.e. =\<1 or at baseline) from adverse events due to agents administered more than 21 days earlier.
- Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 14 days prior to day 1 of therapy or who has not recovered (i.e. =\< 1 or at baseline) from adverse events due to a previously administered agent. \* Note: Subjects with =\< grade 2 neuropathy are an exception and may qualify for the study.
- Antineoplastic biologic therapy or major surgery within 21 days of the first dose of trial medication. If subjects received major surgery more than 21 days ago, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- Received live vaccine within 30 days prior to day 1 of protocol therapy.
- Systemic steroid therapy or on any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Diagnosis of immunodeficiency.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Congestive heart failure class III/IV according to the New York Heart Association (NYHA) Functional classification.
- Known severe hypersensitivity reaction to pembrolizumab, pralatrexate, leucovorin or any excipients.
- Active autoimmune disease that has required systemic treatment in the past 2 years (replacement therapies for hormone deficiencies are allowed). Hemolytic anemia associated with the lymphoma does not exclude a patient from the study.
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- City of Hope Medical Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (3)
City of Hope Medical Center
Duarte, California, 91010, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Alex Herrera
- Organization
- City of Hope Medical Center
Study Officials
- PRINCIPAL INVESTIGATOR
Alex F Herrera
City of Hope Medical Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 16, 2018
First Posted
July 26, 2018
Study Start
February 4, 2019
Primary Completion
May 3, 2023
Study Completion
February 26, 2026
Last Updated
June 26, 2025
Results First Posted
August 27, 2024
Record last verified: 2025-06