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

• ClinicalTrials.gov Identifier: NCT03291353
• Recruitment Status: Withdrawn
• First Posted: September 25, 2017
• Last Update Posted: April 19, 2019
• Sponsor: Michael Boyiadzis
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Michael Boyiadzis, University of Pittsburgh

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Refractory Acute Myeloid Leukemia	Drug: pembrolizumab	Early Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 0- Pilot Study of Pembrolizumab on Immune Cells in Patient With Refractory Acute Myeloid Leukemia
• Actual Study Start Date: October 17, 2017
• Estimated Primary Completion Date: August 19, 2019
• Estimated Study Completion Date: August 19, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: AML Patients; pembrolizumab 200 mg given IV once every three weeks	Drug: pembrolizumab; 200 mg IV given every three weeks; Other Name: Keytruda

Outcome Measures

Primary Outcome Measures :

1. Adverse event assessment [ Time Frame: From prior to first dose up to 48 months ]
   Adverse event assessment using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Secondary Outcome Measures :

1. Response Rate (RR) [ Time Frame: Up to greater than or equal to 48 months ]
   The number of patients receiving treatment that experience either a Partial Response (remission) and/or a Complete Response (remission) / the total number of treated patients, per Response Criteria for Acute Leukemia criteria.
2. Overall survival [ Time Frame: Up to greater than or equal to 48 months ]
   Median overall survival will be estimated by the Kaplan-Meier method with 90% confidence intervals.

Other Outcome Measures:

1. Percent change of neutrophils and lymphocytes [ Time Frame: Up to greater than or equal to 48 months ]
   Percent change of neutrophils and lymphocytes from baseline before therapy to follow up
2. Absolute number of CD4+ T cells, CD8+ T cells, Treg , NK cells, B cells and monocytes [ Time Frame: Up to greater than or equal to 48 months ]
   Change in number of CD4+ T cells, CD8+ T cells, Treg , NK cells, B cells and monocytes from baseline before therapy to follow up
3. Absolute number of activated immune effector cells [ Time Frame: Up to greater than or equal to 48 months ]
   Change in number of activated immune effector cells from baseline before therapy to follow up
4. Levels of TGF-beta and NKG2D ligands [ Time Frame: Up to greater than or equal to 48 months ]
   Change in level from baseline before therapy to follow up

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Be willing and able to provide written informed consent/assent for the trial.
2. Be 18 years of age on the day of signing informed consent.
3. 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).
4. Left ventricular ejection fraction (LVEF) ≥ 45%
5. Have a performance status of 0 or 1 on the ECOG Performance Scale.
6. Demonstrate adequate organ function, all screening labs should be performed within 10 days of treatment initiation.
7. 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.
8. 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.
9. 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.

Exclusion Criteria:

1. Has a diagnosis of Acute Promyelocytic Leukemia (APL) as defined by the World Health Organization
2. Relapsed acute myeloid leukemia
3. Bi-lineage or bi-phenotypic leukemias
4. Prior use of clofarabine or fludarabine
5. Previous allogeneic or autologous hematopoietic cell transplantation or solid organ transplantation
6. 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.
7. 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.
8. Has a known history of active TB (Bacillus Tuberculosis)
9. Hypersensitivity to pembrolizumab or any of its excipients.
10. 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.
11. 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.
12. 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.
13. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis and/or has known active central nervous system (CNS) leukemia involvement.
14. 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.
15. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
16. 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.
17. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
18. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
19. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
20. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
21. Has known active Hepatitis B or Hepatitis C.
22. Has received a live vaccine within 30 days of planned start of study therapy.

Contacts and Locations

Locations

United States, Pennsylvania

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States, 15232

Sponsors and Collaborators

Michael Boyiadzis

Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Michael Boyiadzis, MD, MHSc; University of Pittsburgh

More Information

• Responsible Party: Michael Boyiadzis, Associate Professor of Medicine, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT03291353
• Other Study ID Numbers: 17-056
• First Posted: September 25, 2017
• Last Update Posted: April 19, 2019
• Last Verified: April 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms by Histologic Type; Neoplasms; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents