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

NCT03286114 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: UMCC 2017.056HUM00129255
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Myelodysplastic Syndromes; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (3)

• The Number of Patients That Demonstrate Clinical Benefit From Treatment

  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.

  Day 77

• The Number of Patients That Respond to Treatment

  This study will assess the number of patients that respond to treatment by overall response rate (ORR). ORR is defined as the number of patients will complete remission and partial remission. 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.

  Day 77

• Graft Versus Host Disease (GvHD) or Other Significant Immune Mediated Toxicities

  The number of patients that experience Graft Versus Host Disease (GvHD) or other significant immune mediated toxicities

  30 Days Post Treatment

Secondary Outcomes (2)

• Overall Survival

  1 Year

• Event- Free Survival

  1 Year

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

200mg IV every 21 days

Also known as: KEYTRUDA

Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of Michigan Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• Magenau JM, Frame DG, Riwes M, Maciejewski J, Anand S, Pawarode A, Perry AM, Geer M, Braun T, Ghosh M, Reddy P. PD-1 inhibition for relapse after allogeneic transplantation in acute myeloid leukemia and myelodysplastic syndrome. Blood Adv. 2025 Aug 12;9(15):3878-3886. doi: 10.1182/bloodadvances.2024015200.

  PMID: 40198769 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: University of Michigan Rogel Cancer Center ClinicalTrials.gov Admin
• Organization: University of Michigan Rogel Cancer Center

ClinicalTrialsgov_CCAdmin@umich.edu

734-936-9499

Study Officials

• John Magenau, M.D.

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: September 8, 2017
• First Posted: September 18, 2017
• Study Start: December 21, 2017
• Primary Completion: October 22, 2020
• Study Completion: April 28, 2021
• Last Updated: May 11, 2025
• Results First Posted: May 11, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)