Clinical trial NCT03286114: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Myelodysplastic Syndromes
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2017-09-18
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


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

Primary outcomes:
measure: The Number of Patients That Demonstrate Clinical Benefit From Treatment
timeFrame: Day 77
measure: The Number of Patients That Respond to Treatment
timeFrame: Day 77
measure: Graft Versus Host Disease (GvHD) or Other Significant Immune Mediated Toxicities
timeFrame: 30 Days Post Treatment
Secondary outcomes:
measure: Overall Survival
timeFrame: 1 Year
measure: Event- Free Survival
timeFrame: 1 Year
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Cancer Center
state: Michigan
Study officials:
affiliation: University of Michigan Rogel Cancer Center
name: John Magenau, M.D.
role: PRINCIPAL_INVESTIGATOR
References: