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

This study is currently recruiting participants.
Verified April 2017 by University of Chicago
Sponsor:
ClinicalTrials.gov Identifier:
NCT02981914
First Posted: December 5, 2016
Last Update Posted: April 20, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
University of Chicago
  Purpose
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.

Condition Intervention Phase
Classical Hodgkin Lymphoma B-cell Non-Hodgkin Lymphoma Acute Myeloid Leukemia Myelodysplastic Syndromes Drug: Pembrolizumab Early Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Pembrolizumab Treatment for Disease Relapse After Allogeneic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by University of Chicago:

Primary Outcome Measures:
  • Number of patients with adverse events [ Time Frame: 24 months ]
    To determine the tolerability of pembrolizumab treatment in the setting of relapsed myeloid malignancies and mature B cell lymphomas following alloSCT.


Secondary Outcome Measures:
  • Time between initial response and subsequent disease progression or relapse [ Time Frame: From date of therapy until the date of first documented progression or relapse, whichever came first, assessed up to 100 months ]
    To determine the duration of response (DOR) of patients treated with pembrolizumab in the setting of relapsed myeloid malignancies and mature B cell lymphomas following alloSCT.

  • Time between first documentation of complete remission (CR) or partial remission (PR) (by IRC) to the first documentation of disease progression or death by any cause [ Time Frame: From the date of first documented of CR or PR to the first documented progression or date of death from any cause, whichever came first, assessed up to 100 months ]
    To determine the overall response rate (ORR) of patients treated with pembrolizumab in the setting of relapsed myeloid malignancies and mature B cell lymphomas following alloSCT, stratified by disease type.

  • Time between the start of therapy to death from any cause. [ Time Frame: From start date of therapy to the date of death from any cause, whichever may come first, assessed up to 100 months ]
    To determine the overall survival (OS) of patients treated with pembrolizumab in the setting of relapsed myeloid malignancies and mature B cell lymphomas following alloSCT.


Other Outcome Measures:
  • Effect on restoring donor chimerism [ Time Frame: 24 months ]
    To determine the effect of pembrolizumab on restoring donor chimerism in patients with relapsed myeloid malignancies and mature B cell lymphomas following alloSCT.

  • Effect of pembrolizumab on the numbers and activations status of peripheral blood T cells [ Time Frame: 24 months ]
  • Compare PD-L1 expression on malignant cells at initial diagnosis and at disease relapse following alloSCT [ Time Frame: 24 months ]
  • Effect of pembrolizumab on the T cell receptor (TCR) repertoire in the peripheral blood, and where available, tumor environment, following alloSCT [ Time Frame: 24 months ]

Estimated Enrollment: 26
Actual Study Start Date: March 7, 2017
Estimated Study Completion Date: February 2020
Estimated Primary Completion Date: February 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Pembrolizumab
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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

    1. Signed written informed consent

      1. 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.
      2. Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study.
    2. Target population

      1. Subjects must be ≥ 18 years of age.
      2. Subjects must have an ECOG performance status of 0-1 (Appendix).
      3. 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.
      4. 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.
      5. Subjects must be off of all immunosuppressive medications for a minimum of 2 weeks with the exception of physiologic doses of corticosteroids.
      6. 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.
      7. Subjects must not have had any prior investigational agents or devices within 4 weeks of beginning study drug
      8. Subjects must have no prior history of VOD
      9. Subjects must demonstrate adequate organ function as defined in Table 2. All screening labs should be performed within 10 days of treatment initiation.

        Table 2. Adequate Organ Function Laboratory Values

        System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥ 500 /mcL Platelets ≥ 50,000 /mcL Hemoglobin ≥ 8 g/dL (RBC transfusions are OK)

        Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤ 1.5 X upper limit of normal (ULN) or

        • 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN

        Hepatic Serum total bilirubin ≤ 1.5 X ULN or direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5X ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN Albumin > 2.0 mg/dL

        Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy, in which case, the PT/INR should be within therapeutic range for intended use. Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy, in which case, the PTT should be within therapeutic range for intended use.

        *Creatinine clearance should be calculated per institutional standard.

      10. Female subjects of childbearing potential should have a negative urine or serum pregnancy test (β-hCG) within 72 hours prior to receiving the first dose of study medication.
      11. Female subjects with childbearing potential should be willing to use 2 methods of contraception, be surgically sterile, or abstain from heterosexual activity throughout the course of the study, until 120 days after the final dose of study medication. Subjects with childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. Abstinence is acceptable if this is the established and preferred contraceptive method for the subject (see Section 6.7.1).
      12. Male subjects should agree to use an adequate method of contraception starting with the first dose of study medication until 120 days after the final dose of study medicine. Abstinence is acceptable if this is the established and preferred contraceptive method for the subject (see Section 6.7.1).

Exclusion Criteria:

  • 1. Target disease exclusions

    1. Subjects must not have known central nervous system involvement by disease (parenchymal, meningeal or cerebrospinal fluid) 2. Medical history, concurrent diseases, and prior treatments
    1. Subjects must not have a history of any positive test for hepatitis B or hepatitis C indicating active disease or previous exposure.
    2. Subjects must not have a history of human immunodeficiency virus (HIV) infection.
    3. 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.
    4. Subjects must not be concurrently receiving disease-modifying therapy in another therapeutic investigational study.
    5. 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.
    6. 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.
    7. Subjects must not have received a donor lymphocyte infusion (DLI) within 8 weeks prior to the first dose of study medication.
    8. 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).
    9. 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.
    10. 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).
    11. 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.
    12. 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.
    13. Subjects must not have a known active infection requiring intravenous antibiotic therapy.
    14. Subjects must not have a history of (non-infectious) pneumonitis that required steroid treatment, evidence of interstitial lung disease, or active, non-infectious pneumonitis. Subjects must not have active, non-infectious colitis.
    15. Subjects must not be pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the final dose of study medication.
    16. Subjects must not have received a live vaccine within 30 days prior to the first dose of study medication.
    17. Subjects must not be or have an immediate family member (spouse, parent, legal guardian, sibling or child) who is an investigational site sponsor or staff directly involved with the trial, unless IRB approval is granted previously.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02981914


Contacts
Contact: Alexis Small 7737029440 asmall@medicine.bsd.uchicago.edu

Locations
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Alexis Small    773-702-9440    asmall@medicine.bsd.uchicago.edu   
Principal Investigator: Justin Kline, MD         
Sponsors and Collaborators
University of Chicago
  More Information

Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT02981914     History of Changes
Other Study ID Numbers: IRB16-1195
First Submitted: November 30, 2016
First Posted: December 5, 2016
Last Update Posted: April 20, 2017
Last Verified: April 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Chicago:
Classical Hodgkin Lymphoma
B-cell Non-Hodgkin Lymphoma
Acute Myeloid Leukemia
Myelodysplastic Syndromes
pembrolizumab

Additional relevant MeSH terms:
Lymphoma
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Lymphoma, Non-Hodgkin
Hodgkin Disease
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Pembrolizumab
Antineoplastic Agents