Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Pembrolizumab 200 mg is administered IV once as monotherapy, 14 days after the initiation of HiDAC salvage induction chemotherapy. Patients who have a response (i.e., PR/CR/CRi) to induction phase will receive maintenance pembrolizumab at 200 mg IV every 3 weeks for up to 2-years of maintenance therapy (i.e., beginning on day 1 of maintenance). Patients who are ineligible for pembrolizumab administration by day 21 will be removed from the study.

Pembrolizumab 200 mg is administered IV once as monotherapy, 14 days after the initiation of HiDAC salvage induction chemotherapy. Patients who have a response (i.e., PR/CR/CRi) to induction phase will receive maintenance pembrolizumab at 200 mg IV every 3 weeks for up to 2 years of maintenance therapy (i.e., beginning on day 1 of maintenance).

pembrolizumab,

Joshua F Zeidner, MD

Rationale:The purpose of this research study is to test the effectiveness of the standard high dose cytarabine (HiDAC) on days 1 through 5 followed by a single dose of pembrolizumab on day 14 as induction therapy in patients with relapsed and refractory acute myeloid leukemia (AML). Patients who achieve a response to treatment will continue on the study drug (pembrolizumab) every 3 weeks for up to 2 years maintenance therapy.

Purpose:This is a study about a new investigative drug, pembrolizumab (MK-3475) that is being studied in a clinical research trial together with standard chemotherapy (HiDAC) in relapsed and refractory AML. The study will also explore the association between potential immune biomarkers and clinical outcomes with pembrolizumab; therefore all patients will have blood and bone marrow samples collected before and after treatment to determine the dynamic nature of immune signatures pre and post-treatment.

Primary Objective

1. Estimate the objective overall rate of CR (CR+CRi) for age-adjusted HiDAC (age \<60 years: 2 gm/m2 IV Q12hours days 1-5; age \>60 years: 1.5 gm/m2 IV Q12hours days 1-5) followed by pembrolizumab 200 mg IV on day 14 in relapsed and refractory AML patients

Secondary Objectives

1. Estimate the rate of unacceptable toxicity associated with HiDAC followed by pembrolizumab as induction therapy
2. Estimate the objective overall response rates (PR+CR+CRi) for HiDAC followed by pembrolizumab.
3. Characterize the toxicity associated with HiDAC followed by pembrolizumab as induction therapy
4. Characterize the toxicity associated with pembrolizumab 200 mg IV Q3weeks when used as monotherapy maintenance after an initial response to induction phase HiDAC followed by pembrolizumab
5. Estimate the relapse-free survival (RFS) and progression-free survival (PFS) of patients receiving maintenance pembrolizumab
6. Estimate the overall survival (OS) of patients who received induction phase treatment.

High Dose Cytarabine Followed by Pembrolizumab in Relapsed/Refractory AML

LCCC 1522: Phase 2 Study of High Dose Cytarabine Followed by Pembrolizumab in Relapsed and Refractory Acute Myeloid Leukemia

The rate of overall CR includes CR and CR with incomplete recovery (CRi) as defined by the International European LeukemiaNet Guidelines in AML. CR is defined as bone marrow blasts \<5%; absence of Auer rods; absence of extramedullary disease; absolute neutrophil count \>1,000/microliter (mcL); platelet count \>100,000/mcL; independence of red cell transfusions and CRi is defined as meeting all CR criteria except for residual neutropenia (\<1,000/mcL) or thrombocytopenia (\<100,000/mcL) plus independent of platelet transfusions.

number of participants with drug-related grade 3 (severe) non-hematologic toxicity (with exception of infusion reactions, rash, fever, infection, nausea, fatigue, and anorexia) persisting for \>7 days with supportive care, or any drug-related non-hematologic grade \>4 (life-threatening) toxicity (excluding infection). Toxicity will be classified and graded according to National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term ranging from 1 (mild) to 5 (death related to adverse event).

PR+CR+CRi as determined by International European LeukemiaNet Guidelines in AML. PR is defined as bone marrow blasts 5-25% and decrease of pretreatment bone marrow blast % by \>50%; all hematologic criteria of CR. CR is defined as bone marrow blasts \<5%; absence of Auer rods; absence of extramedullary disease; absolute neutrophil count \>1,000/microliter (mcL); platelet count \>100,000/mcL; independence of red cell transfusions and CRi is defined as meeting all CR criteria except for residual neutropenia (\<1,000/mcL) or thrombocytopenia (\<100,000/mcL) plus independent of platelet transfusions.

RFS will be defined as time from day 1 of Complete Remission (CR) or Complete Remission With Incomplete Blood Count Recovery (CRi) to relapse or death from any cause. CR is defined as bone marrow blasts \<5%; absence of Auer rods; absence of extramedullary disease; absolute neutrophil count \>1,000/microliter (mcL); platelet count \>100,000/mcL; independence of red cell transfusions and CRi is defined as meeting all CR criteria except for residual neutropenia (\<1,000/mcL) or thrombocytopenia (\<100,000/mcL) plus independent of platelet transfusions.

PFS will be defined as time from day 1 of response (i.e., PR/CR/CRi) to progression or death from any cause. PR+CR+CRi s determined by International European LeukemiaNet Guidelines in AML. PR is defined as bone marrow blasts 5-25% and decrease of pretreatment bone marrow blast % by \>50%; all hematologic criteria of CR. CR is defined as bone marrow blasts \<5%; absence of Auer rods; absence of extramedullary disease; absolute neutrophil count \>1,000/microliter (mcL); platelet count \>100,000/mcL; independence of red cell transfusions and CRi is defined as meeting all CR criteria except for residual neutropenia (\<1,000/mcL) or thrombocytopenia (\<100,000/mcL) plus independent of platelet transfusions.

OS is defined as time from day 1 of treatment until date of last known follow up or death of any cause

Merck Sharp & Dohme LLC

UNC Lineberger Comprehensive Cancer Center

Pembrolizumab 200 mg is administered IV once as monotherapy, 14 days after the initiation of High dose cytarabine (HiDAC) salvage induction chemotherapy. Subjects who have a response to induction phase will receive maintenance pembrolizumab at 200 mg IV every 3 weeks for up to 2-years of maintenance therapy (beginning on day 1 of maintenance).Subjects who are ineligible for pembrolizumab administration by day 21 will be removed from the study.

Single Arm Pembrolizumab

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Acute myeloid leukemia (AML) is considered to be "refractory" in patients who do not respond to intensive induction chemotherapy. Relapsed AML is the return of leukemia cells after a patient has reached complete remission

Acute myeloid leukemia (AML) type

European LeukemiaNet (ELN) 2017 genetic risk stratification

Risk

Secondary Acute Myeloid Leukemia (AML)

Median Bone Marrow Blast Percentage

One subject is excluded from the analysis population due to an adverse event from the standard of care high dose cytarabine and did not receive any of the treatment of interest (pembrolizumab).

Robin V. Johnson

The Rate of Complete Remission (CR)

Rate of Unacceptable Toxicity

Objective Overall Response Rate: Partial Remission (PR) + Complete Remission (CR) + Complete Remission With Incomplete Blood Count Recovery (CRi) for HiDAC Followed by Pembrolizumab

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
High Dose Cytarabine Followed by Pembrolizumab in Relapsed/Refractory AML	NCT02768792	Acute Myeloid L...	pembrolizumab,	18 Years - 70 Years	UNC Lineberger Comprehensive Cancer Center
High Dose Cytarabine Followed by Pembrolizumab in Relapsed/Refractory AML	NCT02768792	Acute Myeloid L...	pembrolizumab,	18 Years - 70 Years	UNC Lineberger Comprehensive Cancer Center

Spots Global Cancer Trial Database for pembrolizumab,