Pilot Study of Pembrolizumab Treatment for Disease Relapse After Allogeneic Stem Cell Transplantation
Overview
- Phase
- Early Phase 1
- Intervention
- Pembrolizumab
- Conditions
- Classical Hodgkin Lymphoma
- Sponsor
- University of Chicago
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Number of Patients With Dose-limiting Toxicities (DLTs)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This pilot study has been designed to investigate the safety of pembrolizumab treatment for disease relapse following allogeneic stem cell transplant (alloSCT). Pembrolizumab will be administered at a fixed dose of 200 mg IV every 3 weeks. Approximately 12-26 patients with relapsed MDS, AML, or mature B cell (B-NHL, cHL) malignancies that have relapsed following alloSCT will be enrolled on this trial. Pembrolizumab treatment will be administered for up to 24 months, provided that neither disease progression, nor development of a dose-limiting toxicity (DLT), has occurred. Adverse events will be monitored every three weeks throughout the trial and graded in severity according to the guidelines outlined in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. This trial will be conducted in accordance with Good Clinical Practices.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female subjects with AML, MDS or mature B cell lymphomas that have relapsed following matched-related donor (MRD) or matched unrelated donor (MUD) (HLA-A -B -C -DR -DQ) alloSCT are eligible for enrollment
- •Signed written informed consent
- •Subjects must have signed and dated an IRB-approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care.
- •Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study.
- •Target population
- •Subjects must be ≥ 18 years of age.
- •Subjects must have an ECOG performance status of 0-1 (Appendix).
- •Subjects have undergone alloSCT \> 90 days prior to enrollment from a matched-related donor (MRD), matched-unrelated donor (MUD), cord blood donor, or haplo-identical and cord blood donor.
- •There must be histological confirmation of relapse after alloSCT of any of the following diseases: any mature B cell lymphoma (cHL or NHL), AML or MDS.
- •Subjects must be off of all immunosuppressive medications for a minimum of 2 weeks with the exception of physiologic doses of corticosteroids.
Exclusion Criteria
- •Target disease exclusions
- •Subjects must not have known central nervous system involvement by disease (parenchymal, meningeal or cerebrospinal fluid)
- •Medical history, concurrent diseases, and prior treatments
- •Subjects must not have a history of any positive test for hepatitis B or hepatitis C indicating active disease or previous exposure.
- •Subjects must not have a history of human immunodeficiency virus (HIV) infection.
- •Subjects must not be receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks prior to the first dose of study medication. The use of physiologic doses of corticosteroids is acceptable.
- •Subjects must not be concurrently receiving disease-modifying therapy in another therapeutic investigational study.
- •Subjects must not have received a prior monoclonal antibody within 4 weeks prior to the first dose of study medication, and must have recovered (≤ grade 1) from adverse events related to any anti-cancer agent administered \> 4 weeks previous to the first dose of study medication.
- •Subjects must not have received chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of study medication, and must have recovered (≤ grade 1) from adverse events related to a previously administered agent.
- •Subjects must not have received a donor lymphocyte infusion (DLI) within 8 weeks prior to the first dose of study medication.
Arms & Interventions
Pembrolizumab
Pembrolizumab will be administered at a fixed dose of 200 mg IV every 3 weeks. Treatment will be administered for up to 24 months, provided that neither disease progression, nor development of a dose-limiting toxicity (DLT), has occurred.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Number of Patients With Dose-limiting Toxicities (DLTs)
Time Frame: 90 days
A DLT is defined as the development of grade 3 or 4 acute GVHD (defined by the Gluckenberg scale), graft rejection, the development of any unexpected grade \> 2 toxicity felt to be related to pembrolizumab, or the development of \> grade 2 dysfunction of a vital organ felt to be secondary to an immune-related adverse event within 90 days following the initiation of pembrolizumab treatment.
Secondary Outcomes
- Objective Response Rate(24 months)
- Time Between Initial Response and Subsequent Disease Progression or Relapse(From date of response until the date of first documented progression or relapse, whichever came first, assessed up to 12 months)
- Time Between the Start of Therapy to Death From Any Cause.(From start date of therapy to the date of death from any cause, whichever may come first, assessed up to 24 months)