Clinical Trials /

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

NCT02981914

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Classical Hodgkin Lymphoma
  • Mature B-Cell Non-Hodgkin Lymphoma
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pilot Study of Pembrolizumab Treatment for Disease Relapse After Allogeneic Stem Cell Transplantation
  • Official Title: Pilot Study of Pembrolizumab Treatment for Disease Relapse After Allogeneic Stem Cell Transplantation

Clinical Trial IDs

  • ORG STUDY ID: IRB16-1195
  • NCT ID: NCT02981914

Conditions

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

Interventions

DrugSynonymsArms
PembrolizumabPembrolizumab

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.

Trial Arms

NameTypeDescriptionInterventions
PembrolizumabExperimentalPembrolizumab 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.
  • Pembrolizumab

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

               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 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)

                       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.

                   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.

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of patients with adverse events
Time Frame:24 months
Safety Issue:
Description:To determine the tolerability of pembrolizumab treatment in the setting of relapsed myeloid malignancies and mature B cell lymphomas following alloSCT.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Chicago

Trial Keywords

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

Last Updated

October 7, 2019