Phase 0- Pilot Study of Pembrolizumab on Immune Cells in Patient With Refractory Acute Myeloid Leukemia

NCT03291353 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: 17-056
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, single-arm, pilot trial to evaluate the immune effects, safety and tolerability of pembrolizumab in subjects newly diagnosed with acute myeloid leukemia (AML) who have persistent leukemia after induction chemotherapy. Patients must have an ECOG performance status of 0-1. The enrollment target for this study is 10 patients.

Conditions

Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Adverse event assessment

  Adverse event assessment using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  From prior to first dose up to 48 months

Secondary Outcomes (2)

• Response Rate (RR)

  Up to greater than or equal to 48 months

• Overall survival

  Up to greater than or equal to 48 months

Other Outcomes (4)

• Percent change of neutrophils and lymphocytes

  Up to greater than or equal to 48 months

• Absolute number of CD4+ T cells, CD8+ T cells, Treg , NK cells, B cells and monocytes

  Up to greater than or equal to 48 months

• Absolute number of activated immune effector cells

  Up to greater than or equal to 48 months

Study Arms (1)

AML Patients

EXPERIMENTAL

pembrolizumab 200 mg given IV once every three weeks

Drug: pembrolizumab

Interventions

pembrolizumab DRUG

200 mg IV given every three weeks

Also known as: Keytruda

AML Patients

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Be 18 years of age on the day of signing informed consent.
• Patients with newly diagnosed AML based on the World Health Organization classification (21) who have persistent leukemia after a course or more of treatment with induction chemotherapy (the diagnosis of persistent disease, which is defined as \>10% blasts by evaluation of bone marrow biopsy or bone marrow aspirate).
• Left ventricular ejection fraction (LVEF) ≥ 45%
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Demonstrate adequate organ function, all screening labs should be performed within 10 days of treatment initiation.
• 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. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential must be willing to use an adequate method of contraception- Contraception, for the course of the study through 120 days after the last dose of study medication.
• Male subjects of childbearing potential must agree to use an adequate method of contraception- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.

You may not qualify if:

• Has a diagnosis of Acute Promyelocytic Leukemia (APL) as defined by the World Health Organization
• Relapsed acute myeloid leukemia
• Bi-lineage or bi-phenotypic leukemias
• Prior use of clofarabine or fludarabine
• Previous allogeneic or autologous hematopoietic cell transplantation or solid organ transplantation
• Is currently participating in and receiving study therapy, or has participated in a study of an investigational agent and received study therapy, or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• 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 (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Concurrent active malignancy; exceptions include patients who have been disease free for 5 years, patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma, or patients with another malignancy that is indolent or definitively treated.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis and/or has known active central nervous system (CNS) leukemia involvement.
• Has active 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.

Sponsors & Collaborators

• Michael Boyiadzis: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Michael Boyiadzis, MD, MHSc

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: June 19, 2017
• First Posted: September 25, 2017
• Study Start: October 17, 2017
• Primary Completion: August 19, 2019
• Study Completion: August 19, 2022
• Last Updated: April 19, 2019

Record last verified: 2019-04

Locations

US (1)