Pilot Study of Pembrolizumab Treatment for Disease Relapse After Allogeneic Stem Cell Transplantation

NCT02981914 | Completed Early Phase 1 Results FDA Drug

• 1 other identifier: IRB16-1195
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Classical Hodgkin Lymphoma; B-cell Non-Hodgkin Lymphoma; Acute Myeloid Leukemia; Myelodysplastic Syndromes

Keywords

Classical Hodgkin Lymphoma; B-cell Non-Hodgkin Lymphoma; Acute Myeloid Leukemia; Myelodysplastic Syndromes; pembrolizumab

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Dose-limiting Toxicities (DLTs)

  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.

  90 days

Secondary Outcomes (3)

• 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

• Objective Response Rate

  24 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

Other Outcomes (4)

• Effect on Restoring Donor Chimerism

  24 months

• Effect of Pembrolizumab on the Numbers and Activations Status of Peripheral Blood T Cells

  24 months

• Compare PD-L1 Expression on Malignant Cells at Initial Diagnosis and at Disease Relapse Following alloSCT

  24 months

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

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.

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Pembrolizumab will be administered at a fixed dose of 200 mg IV every 3 weeks for a max of 24 months, so long as there is no disease progression.

Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Subjects with B cell lymphoma must have measurable disease, defined as at least 1 lesion that can be accurately measured in at least 2 dimensions with CT scan. Minimum measurement must be \> 15 mm in the longest diameter and \> 10 mm in the short axis.
• Subjects must not have had any prior investigational agents or devices within 4 weeks of beginning study drug
• Subjects must have no prior history of VOD
• Subjects must demonstrate adequate organ function as defined below. All screening labs should be performed within 10 days of treatment initiation.
• Hematological Absolute neutrophil count (ANC) ≥ 500 /mcL Platelets ≥ 20,000 /mcL Hemoglobin ≥ 8 g/dL (RBC transfusions are OK)

You may not qualify if:

• Subjects must not have known central nervous system involvement by disease (parenchymal, meningeal or cerebrospinal fluid) 2. Medical history, concurrent diseases, and prior treatments
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• 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.
• Subjects must not have a history of severe (grade 3-4) acute GVHD, and/or current \> grade 1 acute GHVD. Subjects must not have a history of chronic GVHD (whether limited or extensive stage).
• Subjects must not have autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Subjects must not have a known history of congestive heart failure, unstable angina pectoris, or cardiac arrhythmia (with the exception of chronic and rate-controlled atrial fibrillation).
• Subjects must not have a history of other serious underlying medical or psychiatric condition that, in the opinion of the investigator, would impair the ability to receive, tolerate and or comply with the planned treatment and follow-up.
• Subjects must not have a history of a known secondary primary malignancy that is not in remission and/or that requires active therapy. Exceptions include non-melanoma skin cancers and in situ cervical cancer that has undergone curative-intent local therapy.
• Subjects must not have a known active infection requiring intravenous antibiotic therapy.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Related Publications (1)

• Godfrey J, Liu H, Yu J, Tallarico M, Curran E, Artz A, Riedell PA, Stock W, Karrison T, Fitzpatrick C, Venkataraman G, Cooper A, Smith SM, Bishop MR, Kline J. Pembrolizumab for the treatment of disease relapse after allogeneic hematopoietic stem cell transplantation. Blood Adv. 2023 Mar 28;7(6):963-970. doi: 10.1182/bloodadvances.2022008403.

  PMID: 35973200 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia; Hematologic Diseases; Bone Marrow Diseases

Results Point of Contact

• Title: Theodore Karrison (Research Professor)
• Organization: University of Chicago

karrisont@nrgoncology.org

773-702-9326

Study Officials

• Justin Kline, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2016
• First Posted: December 5, 2016
• Study Start: March 7, 2017
• Primary Completion: October 9, 2020
• Study Completion: November 1, 2020
• Last Updated: April 22, 2024
• Results First Posted: April 22, 2024

Record last verified: 2023-11

Locations

US (1)