A Phase 1/2 Study of Pembrolizumab Plus Pralatrexate for Treatment of Relapsed or Refractory Peripheral T-Cell Lymphomas
Overview
- Phase
- Phase 1
- Intervention
- Pembrolizumab
- Conditions
- Anaplastic Large Cell Lymphoma
- Sponsor
- City of Hope Medical Center
- Enrollment
- 13
- Locations
- 3
- Primary Endpoint
- Number of Participants Who Had Dose Limiting Toxicities
- Status
- Active, not recruiting
- Last Updated
- 10 months ago
Overview
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.
Detailed Description
PRIMARY OBJECTIVES: I. Evaluate the safety and tolerability of a regimen combining pembrolizumab and pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). II. Establish the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of the combined pralatrexate and pembrolizumab regimen. III. Estimate the overall response rate (ORR) according to the Lugano Classification in patients treated with pembrolizumab plus pralatrexate at the RP2D. SECONDARY OBJECTIVES: I. Estimate the complete response (CR) rate according to the Lugano Classification duration of response (DOR), overall survival (OS) and progression-free survival (PFS) in patients treated with pembrolizumab plus pralatrexate. II. Estimate the ORR and CR rate according to the International Harmonization Project response criteria. III. Evaluate responses and disease progression according to the Lymphoma Response to Immunomodulatory therapy Criteria (LYRIC). EXPLORATORY OBJECTIVE: I. Explore immunologic and genomic biomarkers of response to pembrolizumab plus pralatrexate therapy. OUTLINE: This is a phase I, dose-escalation study of pralatrexate followed by a phase II study. Patients receive pralatrexate intravenously (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. After completion of study treatment, patients are followed up at 30 and 90 days, every 12 weeks for 1 year, and then every 18 weeks thereafter.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
- •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
Exclusion Criteria
- •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.
Arms & Interventions
Treatment (pralatrexate and pembrolizumab)
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.
Intervention: Pembrolizumab
Treatment (pralatrexate and pembrolizumab)
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.
Intervention: Pralatrexate
Outcomes
Primary Outcomes
Number of Participants Who Had Dose Limiting Toxicities
Time Frame: From the start of Cycle 1 through the start of Cycle 3 (approximately 42 days)
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).
Number of Participants Who Had Overall Response
Time Frame: Up to 43 months after the initial study treatment.
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.
Secondary Outcomes
- 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).)