Study of Azacitidine in Combination With Pembrolizumab in R/R AML Patients and in Newly Diagnosed Older Patients

NCT02845297 | Completed Phase 2 Results

• 2 other identifiers: J1651IRB00098812
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 3

Brief Summary

This is a multicenter, nonrandomized, open-label phase 2 study (with a safety run-in phase) of azacitidine (AZA) 75 mg/m2 given IV or SQ on days 1-7 every 28 days in combination with pembrolizumab 200 mg given IV every 3 weeks (starting on day 8 of cycle 1). The dose/schedule of AZA selected for this study is FDA approved for patients with MDS/AML.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Maximal Tolerable Dose of Pembrolizumab for Cohort 1

  The primary objective is to determine the safe and tolerable dose for both the relapsed/refractory AML patients.

  3- 28 day cycles

Secondary Outcomes (1)

• Number of Participants Who Had Complete Remission/Complete Remission With Incomplete Recovery

  3-28 day cycles

Study Arms (2)

Safety Run In Phase (only Cohort 1):

EXPERIMENTAL

The treatment of relapsed and refractory AML patients.

Drug: pembrolizumab; Drug: Azacitadine

Cohort 2

EXPERIMENTAL

The treatment of newly diagnosed AML patients (≥ 65 years) who are not candidates for intensive induction chemotherapy.

Drug: pembrolizumab; Drug: Azacitadine

Interventions

pembrolizumab DRUG

Intravenous pembrolizumab

Also known as: MK-3475

Cohort 2; Safety Run In Phase (only Cohort 1):

Azacitadine DRUG

Intravenous or subcutaneous

Also known as: Vidaza

Cohort 2; Safety Run In Phase (only Cohort 1):

Eligibility Criteria

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

You may qualify if:

• Cohort #1
• Have histologically or cytologically confirmed relapsed or refractory AML (i.e. ≥5% blasts by manual differential on bone marrow aspirate/biopsy/flow cytometry), excluding acute promyelocytic leukemia (APL; FAB M3; t(15;17))
• Be willing and able to provide written informed consent/assent for the trial.
• Be \> 18 years of age on day of signing informed consent.
• Not be appropriate candidate for intensive salvage chemotherapy due to co-morbidities or other disease- or treatment-related factors.
• NOTE: Subjects who received prior treatment with hypomethylating agents either for Myelodysplastic Syndrome (MDS), Myeloproliferative Neoplasm (MPN), or AML will be eligible if they achieved response to hypomethylating agents in the past (PR or CR) and did not progress while receiving therapy with hypomethylating agents.
• NOTE: Subjects who had prior allogeneic stem cell transplant (alloHSCT) will be eligible as long as they have been at least 3 months after allogeneic HSCT and are off of all immune suppression for at least 3 weeks (\>21 days) and have no evidence of active graft versus host disease (GVHD). Subjects with prior alloHSCT will NOT be eligible for enrollment during the safety run in phase.
• Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 14 days of treatment initiation.
• ECOG performance status ≤ 2.
• A projected life expectancy of at least 12 weeks.
• 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 (Section 5.8.2) must be willing to use an adequate method of contraception as outlined in Section 5.8.2 - Contraception, for the course of the study through 120 days after the last dose of study medication.
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Male subjects of childbearing potential (Section 5.8.2) must agree to use an adequate method of contraception as outlined in Section 5.8.2- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

You may not qualify if:

• Cohort #1
• Is currently participating 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.
• NOTE: Subjects who were treated on a clinical study of allogeneic stem cell transplant (alloHSCT) will be eligible if they are at least 3 months after allogeneic HCT and are at least 3 weeks (\>21 days) off of all immune suppression and have no evidence of active GVHD (physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency is allowed). Subjects with prior alloHSCT will not be eligible for enrollment during the safety run in phase.
• 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 or growth factors within 1 week 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.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) leukemia. Subjects with previously treated CNS leukemia may participate provided that they have documented clearance of CNS leukemia and are not actively treated with intrathecal chemotherapy.
• 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. Subjects that require intermittent use of bronchodilators or local steroid injections will not be excluded from the study.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active uncontrolled infection requiring systemic therapy (viral, bacterial or fungal). Patients with infection under active treatment and controlled with antibiotics are eligible.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (3)

Johns Hopkins Oncology Center

Baltimore, Maryland, 21231-2410, United States

Location

University of North Carolina Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Medical University of South Carolina Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Related Publications (1)

• Rutella S, Vadakekolathu J, Mazziotta F, Reeder S, Yau TO, Mukhopadhyay R, Dickins B, Altmann H, Kramer M, Knaus HA, Blazar BR, Radojcic V, Zeidner JF, Arruda A, Wang B, Abbas HA, Minden MD, Tasian SK, Bornhauser M, Gojo I, Luznik L. Immune dysfunction signatures predict outcomes and define checkpoint blockade-unresponsive microenvironments in acute myeloid leukemia. J Clin Invest. 2022 Nov 1;132(21):e159579. doi: 10.1172/JCI159579.

  PMID: 36099049 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

pembrolizumab; Azacitidine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Dr. Ivana Gojo
• Organization: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

igojo1@jhmi.edu

410-502-8775

Study Officials

• Ivana Gojo, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2016
• First Posted: July 27, 2016
• Study Start: July 1, 2016
• Primary Completion: April 1, 2022
• Study Completion: December 1, 2022
• Last Updated: March 9, 2023
• Results First Posted: March 1, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)