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

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.
 
ClinicalTrials.gov Identifier: NCT03286114
Recruitment Status : Recruiting
First Posted : September 18, 2017
Last Update Posted : April 4, 2022
Sponsor:
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

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.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes Acute Myeloid Leukemia Acute Lymphoblastic Leukemia Drug: Pembrolizumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 21, 2017
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : November 2022


Arm Intervention/treatment
Experimental: Pembrolizumab Drug: Pembrolizumab
200mg IV every 21 days
Other Name: KEYTRUDA




Primary Outcome Measures :
  1. The number of patients that demonstrate clinical benefit from treatment [ Time Frame: Day 77 ]

    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.


  2. The number of patients that respond to treatment [ Time Frame: Day 77 ]

    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.


  3. The number of patients that experience Graft Versus Host Disease (GvHD) or other significant immune mediated toxicities [ Time Frame: 30 Days Post Treatment ]

Secondary Outcome Measures :
  1. The number of patients alive at 1 year [ Time Frame: 1 Year ]
  2. The number of patients alive at 1 year without disease [ Time Frame: 1 Year ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

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): NCT03286114


Contacts
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Contact: John Magenau, M.D. 734-936-8785 johnmage@umich.edu

Locations
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United States, Michigan
University of Michigan Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: John M Magenau, MD    734-936-8785    johnmage@med.umich.edu   
Principal Investigator: John M Magenau, MD         
Sponsors and Collaborators
University of Michigan Rogel Cancer Center
Investigators
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Principal Investigator: John Magenau, M.D. University of Michigan Rogel Cancer Center
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Responsible Party: University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier: NCT03286114    
Other Study ID Numbers: UMCC 2017.056
HUM00129255 ( Other Identifier: University of Michigan )
First Posted: September 18, 2017    Key Record Dates
Last Update Posted: April 4, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents