Clinical Trials /

Augmentation of the Graft vs. Leukemia Effect Via Checkpoint Blockade With Pembrolizumab

NCT03286114

Description:

This is a single arm, open-label, Phase 1b study of pembrolizumab for patients with myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL) whose disease has relapsed after receiving allogeneic hematopoetic stem cell transplant.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Augmentation of the Graft vs. Leukemia Effect Via Checkpoint Blockade With Pembrolizumab
  • Official Title: Augmentation of the Graft vs. Leukemia Effect Via Checkpoint Blockade With Pembrolizumab for Relapse of Primary Malignancy After Allogeneic Hematopoietic Stem Cell Transplant: A Feasibility Study

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2017.056
  • SECONDARY ID: HUM00129255
  • NCT ID: NCT03286114

Conditions

  • Myelodysplastic Syndromes
  • Acute Myeloid Leukemia
  • Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
PembrolizumabKEYTRUDAPembrolizumab

Purpose

This is a single arm, open-label, Phase 1b study of pembrolizumab for patients with myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL) whose disease has relapsed after receiving allogeneic hematopoetic stem cell transplant.

Trial Arms

NameTypeDescriptionInterventions
PembrolizumabExperimental
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL) or Myelodysplastic
             Syndrome (MDS) in confirmed relapse

          -  Confirmation of 'measurable disease'

          -  Patient may not have received definitive salvage chemotherapy for their
             post-transplant relapse within the past 21 days.

          -  Be willing and able to provide written informed consent/assent for the trial

          -  Be ≥ 18 years of age on day of signing informed consent

          -  Be willing to provide tissue from bone marrow biopsies

          -  Have a performance status of 0, to 1 on the ECOG Performance Scale. Eastern
             Cooperative Oncology Group Performance Status: an attempt to quantify cancer patients'
             general well-being and activities of daily life. The score ranges from 0 to 5 where 0
             is asymptomatic and 5 is death.

          -  Demonstrate adequate organ function

          -  Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication.

          -  Female subjects of childbearing potential must be willing to use an adequate method of
             contraception

          -  Male subjects of childbearing potential must agree to use an adequate method of
             contraception

        Exclusion Criteria:

          -  Has had relapse prior to primary neutrophil engraftment or ≤21 days post HCT.

          -  Has received >1 line of chemotherapy or other treatment directed towards
             post-transplant relapse prior to study entry

          -  Rapidly progressive relapse requiring urgent chemotherapy as determined by treating
             physician

          -  Is currently participating and receiving study therapy of an investigational agent and
             received study therapy within 2 weeks of the first dose of treatment.

          -  Has a diagnosis of active GvHD (≥ Grade I)

          -  Receiving systemic steroid therapy of > 10mg prednisone daily or equivalent*

          -  Has received GM-CSF within 14 days of first dose of pembrolizumab

          -  Has a known history of active TB (Bacillus Tuberculosis)Hypersensitivity to
             pembrolizumab or any of its excipients

          -  Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
             Day 1 or who has not recovered from adverse events

          -  Has had prior chemotherapy within 21 days or radiation therapy within 14 days prior to
             study Day 1 or who has not recovered from adverse events

          -  Has a known additional (secondary) malignancy that is progressing or requires active
             treatment

          -  Has known or suspected active central nervous system (CNS) metastases and/or
             carcinomatous meningitis

          -  Has a history of (non-infectious) pneumonitis that required steroids, or current
             pneumonitis

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent

          -  Has a known history of Human Immunodeficiency Virus (HIV)

          -  Has known active Hepatitis B or Hepatitis C

          -  Has received a live vaccine within 30 days of planned start of study therapy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The number of patients that demonstrate clinical benefit from treatment
Time Frame:Day 77
Safety Issue:
Description:This study will assess if the study drug is promising for further study. The study drug will be considered promising if at least 4 patients receive a clinical benefit or if any complete response is seen. Clinical benefit is defined as either stable disease, partial remission or complete remission to treatment. Complete remission (CR) will be defined as achieving a morphologic leukemia free state by achieving all of the following criteria: bone marrow myeloblasts < 5% by morphologic assessment; AND absence of circulating blasts with phenotypic or morphologic features of leukemia (e.g. Auer rods) AND no evidence of extramedulary disease. Partial remission (PR) will be defined as a ≥ 50% reduction in bone marrow blast percentage to 5-25% or marrow blasts < 5% with persistent Auer rods, flow cytometric or cytogenetic disease. SD will be defined as ≤ 5% increase in blasts or decreased blast percentage in the bone marrow that does not meet the criteria for PR.

Secondary Outcome Measures

Measure:The number of patients alive at 1 year
Time Frame:1 Year
Safety Issue:
Description:
Measure:The number of patients alive at 1 year without disease
Time Frame:1 Year
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Michigan Rogel Cancer Center

Last Updated

April 16, 2019