High Dose Cytarabine Followed by Pembrolizumab in Relapsed/Refractory AML

• Sponsor: UNC Lineberger Comprehensive Cancer Center (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02768792
• Collaborator: Merck Sharp & Dohme LLC (Industry)
• Enrollment: 38
• Locations: 2
• Arm: 1
• Anticipated Duration (Months): 98.3
• Patients Per Site: 19
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia, in Relapse	Drug: pembrolizumab,	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: LCCC 1522: Phase 2 Study of High Dose Cytarabine Followed by Pembrolizumab in Relapsed and Refractory Acute Myeloid Leukemia
• Actual Study Start Date: Aug 22, 2016
• Actual Primary Completion Date: Nov 27, 2019
• Anticipated Study Completion Date: Nov 1, 2024

Arms and Interventions

Arm

Intervention/Treatment

Other: open-label, multicenter, single-arm 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.

Drug: pembrolizumab,; 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).; Other Names: KEYTRUDA MK-3475

Outcome Measures

Primary Outcome Measures

1. The Rate of Complete Remission (CR) [Day 14 until 2 years complete on study treatment and after full hematologic recovery from HiDAC followed by pembrolizumab]

   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.

Secondary Outcome Measures

1. Rate of Unacceptable Toxicity [Day 14 until 2 years complete on study treatment]

   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).

2. Objective Overall Response Rate: Partial Remission (PR) + Complete Remission (CR) + Complete Remission With Incomplete Blood Count Recovery (CRi) for HiDAC Followed by Pembrolizumab [Day 14 until 2 years complete on study treatment]

   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.

3. Median Relapse-free Survival (RFS) of Patients Receiving Maintenance Pembrolizumab [from Day 1 of complete remission up to 7 years of follow-up (a median of 7.8 months of survivor follow-up at time of reporting)]

   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.

4. Median Progression-free Survival (PFS) of Patients Receiving Maintenance Pembrolizumab. [from Day 1 of response up to 7 years of follow-up (a median of 7.8 months of survivor follow-up at time of reporting)]

   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.

5. Median Overall Survival (OS) of Patients Who Received Induction Phase of Treatment. [from Day 1 of treatment up to 7 years of follow-up (with a median of 7.8 months of follow-up at time of reporting)]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Willing and able to provide written informed consent for the trial

2. 18 years and < 70 years of age on day of signing informed consent

3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

4. Have histologically or cytologically confirmed recurrent AML as defined by ≥5 % myeloblasts in the bone marrow aspirate and or biopsy.

5. Must have received at least 1 cycle of induction therapy for front-line AML including cytarabine continuous infusion + anthracycline +/- cladribine or etoposide for 1 or 2 cycles, or liposomal cytarabine and daunorubicin (CPX-351), or high dose cytarabine with or without fludarabine, cladribine or clofarabine, > 4 cycles of azacitidine/decitabine or the equivalent experimental therapy (the latter as confirmed by the PI)

6. Cytoreduction allowed with hydroxyurea and/or leukapheresis for up to 14 days prior to D1 of treatment under LCCC1522. Patients must be off hydroxyurea for > 12 hours prior to D1 of treatment under LCCC1522

7. Demonstrate adequate organ function as defined below. All screening labs should be performed within 14 days of D1 of treatment under LCCC1522.

Serum creatinine ≤1.5 X upper limit of normal (ULN) OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl)-- ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN Serum total bilirubin ≤ 1.5 X ULN unless due to Gilbert's Disease, hemolysis or leukemic infiltration OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN Aspartate Aminotransferase (AST)(SGOT) and Alanine Aminotransferase (ALT) (SGPT) ≤ 5 X ULN International Normalized Ratio (INR) or Prothrombin Time (PT)- ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants or patient has disseminated intravascular coagulation deemed by investigator to be due to leukemia Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants or patient has disseminated intravascular coagulation deemed by investigator to be due to leukemia

1. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of HiDAC treatment and again prior to D1 of pembrolizumab treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

2. Female subjects of childbearing potential should be willing to use adequate method of contraception for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. The two birth control methods can be two barrier methods or a barrier method plus a hormonal method to prevent pregnancy. Subjects should start using birth control from the screening visit throughout the study period up to 120 days after the last dose of study therapy.

Note: Abstinence is acceptable if this is the usual lifestyle preferred contraception for the subject.

1. Male subjects must agree to use an adequate method of contraception starting with D1 of HiDAC 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.

1. As determined by the enrolling physician or protocol designee, ability of the patient to understand and comply with study procedures

Exclusion Criteria:

1. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.

2. 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 HiDAC treatment. Note: use of steroid eye drops starting at the time of HiDAC administration is allowed.

3. Has a known history of active Bacillus Tuberculosis (TB)

4. Hypersensitivity to pembrolizumab or any of its excipients

5. Has had a prior monoclonal antibody 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.

6. 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. 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.

1. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer that has undergone potentially curative therapy.

2. Has known active central nervous system (CNS) leukemia; subjects with previously treated CNS disease may participate provided they are stable (without evidence of active disease by imaging for at least 4 weeks prior to the first dose of treatment, and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to D1 of treatment.

3. 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.

4. Has evidence of interstitial lung disease or a history of ( non-infectious) pneumonitis that required steroids or current pneumonitis.

5. 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.

6. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

7. 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

8. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)

9. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

10. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., hepatitis C virus (HCV) RNA qualitative is detected).

11. Has received a live vaccine within 30 days prior to the first dose of trial treatment Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed

12. Has uncontrolled intercurrent illness including, but not limited to, active and uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, and uncontrolled symptomatic cardiac arrhythmia. Patients with infection under active treatment and controlled with antibiotics are eligible.

13. Diagnosed with acute promyelocytic leukemia (APL, M3)

14. Receipt of previous allogeneic stem cell transplant; receipt of previous autologous transplant for AML or non-AML condition is allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins School of Medicine The Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland	United States	21205
2	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295

Sponsors and Collaborators

• UNC Lineberger Comprehensive Cancer Center
• Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Joshua F Zeidner, MD, Lineberger Comprehensive Cancer Center University of North Carolina

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 2, 2018

More Information

Additional Information:

• Web address for UNC Lineberger Comprehensive Cancer Center

Publications

None provided.

• Responsible Party: UNC Lineberger Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT02768792
• Other Study ID Numbers: LCCC 1522
• First Posted: May 11, 2016
• Last Update Posted: Aug 12, 2022
• Last Verified: Aug 1, 2022

• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Pembrolizumab

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from two cancer centers between August 2016 and April 2019.
Pre-assignment Detail	A total of 62 subjects were consented to screen for eligibility. Of these, 19 were determined to be ineligible and 5 withdrew consent prior to starting the study.

Arm/Group Title	Single Arm Pembrolizumab
Arm/Group Description	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.
Period Title: Overall Study
STARTED	38
COMPLETED	37
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Single Arm Pembrolizumab
Arm/Group Description	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.
Overall Participants	37
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	54
Sex: Female, Male (Count of Participants)
Female	17 45.9%
Male	20 54.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 5.4%
Not Hispanic or Latino	34 91.9%
Unknown or Not Reported	1 2.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 2.7%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	12 32.4%
White	23 62.2%
More than one race	0 0%
Unknown or Not Reported	1 2.7%
Region of Enrollment (participants) [Number]
United States	37 100%
Acute myeloid leukemia (AML) type (Count of Participants)
Refractory AML	16 43.2%
Relapsed AML	21 56.8%
Risk (Count of Participants)
Favorable	6 16.2%
Intermediate	12 32.4%
Adverse	19 51.4%
Secondary Acute Myeloid Leukemia (AML) (Count of Participants)
Count of Participants [Participants]	13 35.1%
Median Bone Marrow Blast Percentage (percentage of blast cells) [Median (Full Range) ]
Median (Full Range) [percentage of blast cells]	28

Outcome Measures

1. Primary Outcome

Title	The Rate of Complete Remission (CR)
Description	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.
Time Frame	Day 14 until 2 years complete on study treatment and after full hematologic recovery from HiDAC followed by pembrolizumab

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm Pembrolizumab
Arm/Group Description	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.
Measure Participants	37
Count of Participants [Participants]	14 37.8%

2. Secondary Outcome

Title	Rate of Unacceptable Toxicity
Description	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).
Time Frame	Day 14 until 2 years complete on study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm Pembrolizumab
Arm/Group Description	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.
Measure Participants	37
Count of Participants [Participants]	0 0%

3. Secondary Outcome

Title	Objective Overall Response Rate: Partial Remission (PR) + Complete Remission (CR) + Complete Remission With Incomplete Blood Count Recovery (CRi) for HiDAC Followed by Pembrolizumab
Description	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.
Time Frame	Day 14 until 2 years complete on study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm Pembrolizumab
Arm/Group Description	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.
Measure Participants	37
Count of Participants [Participants]	16 43.2%

4. Secondary Outcome

Title	Median Relapse-free Survival (RFS) of Patients Receiving Maintenance Pembrolizumab
Description	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.
Time Frame	from Day 1 of complete remission up to 7 years of follow-up (a median of 7.8 months of survivor follow-up at time of reporting)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm Pembrolizumab
Arm/Group Description	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.
Measure Participants	37
Median (95% Confidence Interval) [Months]	6.9

5. Secondary Outcome

Title	Median Progression-free Survival (PFS) of Patients Receiving Maintenance Pembrolizumab.
Description	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.
Time Frame	from Day 1 of response up to 7 years of follow-up (a median of 7.8 months of survivor follow-up at time of reporting)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm Pembrolizumab
Arm/Group Description	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.
Measure Participants	37
Median (95% Confidence Interval) [Months]	5.7

6. Secondary Outcome

Title	Median Overall Survival (OS) of Patients Who Received Induction Phase of Treatment.
Description	OS is defined as time from day 1 of treatment until date of last known follow up or death of any cause
Time Frame	from Day 1 of treatment up to 7 years of follow-up (with a median of 7.8 months of follow-up at time of reporting)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm Pembrolizumab
Arm/Group Description	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.
Measure Participants	37
Median (95% Confidence Interval) [Months]	8.9

Adverse Events

Time Frame	Day 14 until 2 years complete on study treatment
Arm/Group Title	Single Arm Pembrolizumab
Arm/Group Description	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.
All Cause Mortality
	Single Arm Pembrolizumab
	Affected / at Risk (%)	# Events
Total	32/37 (86.5%)
Serious Adverse Events
	Single Arm Pembrolizumab
	Affected / at Risk (%)	# Events
Total	14/37 (37.8%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other, specify -E.Coli infection in blood	1/37 (2.7%)
Febrile neutropenia	5/37 (13.5%)
Cardiac disorders
Left ventricular systolic dysfunction	1/37 (2.7%)
Gastrointestinal disorders
Abdominal pain	1/37 (2.7%)
General disorders
Fever	1/37 (2.7%)
Hepatobiliary disorders
Cholecystitis	1/37 (2.7%)
Infections and infestations
Catheter related infection	2/37 (5.4%)
Lung infection	4/37 (10.8%)
Meningitis	1/37 (2.7%)
Sepsis	1/37 (2.7%)
Investigations
Alanine aminotransferase increased	2/37 (5.4%)
Aspartate aminotransferase increased	3/37 (8.1%)
Blood bilirubin increased	2/37 (5.4%)
Nervous system disorders
Arachnoiditis	1/37 (2.7%)
Intracranial hemorrhage	1/37 (2.7%)
Transient ischemic attacks	1/37 (2.7%)
Respiratory, thoracic and mediastinal disorders
Pulmonary edema	1/37 (2.7%)
Respiratory failure	1/37 (2.7%)
Vascular disorders
Hypotension	1/37 (2.7%)
Other (Not Including Serious) Adverse Events
	Single Arm Pembrolizumab
	Affected / at Risk (%)	# Events
Total	37/37 (100%)
Blood and lymphatic system disorders
Anemia	32/37 (86.5%)
Febrile neutropenia	24/37 (64.9%)
Hemolysis	1/37 (2.7%)
Cardiac disorders
Atrial fibrillation	1/37 (2.7%)
Chest pain - cardiac	1/37 (2.7%)
Heart failure	1/37 (2.7%)
Mitral valve disease	1/37 (2.7%)
Palpitations	1/37 (2.7%)
Pericardial effusion	1/37 (2.7%)
Sinus bradycardia	2/37 (5.4%)
Sinus tachycardia	8/37 (21.6%)
Supraventricular tachycardia	1/37 (2.7%)
Tricuspid valve disease	1/37 (2.7%)
Ventricular arrhythmia	1/37 (2.7%)
Ear and labyrinth disorders
Ear and labyrinth disorders - Other, specify	2/37 (5.4%)
Vertigo	3/37 (8.1%)
Endocrine disorders
Hyperthyroidism	2/37 (5.4%)
Hypothyroidism	1/37 (2.7%)
Eye disorders
Blurred vision	5/37 (13.5%)
Conjunctivitis	1/37 (2.7%)
Dry eye	4/37 (10.8%)
Eye disorders - Other, specify	1/37 (2.7%)
Eye pain	4/37 (10.8%)
Floaters	1/37 (2.7%)
Photophobia	2/37 (5.4%)
Watering eyes	1/37 (2.7%)
Gastrointestinal disorders
Abdominal pain	8/37 (21.6%)
Ascites	2/37 (5.4%)
Colitis	1/37 (2.7%)
Constipation	14/37 (37.8%)
Diarrhea	16/37 (43.2%)
Dry mouth	2/37 (5.4%)
Esophagitis	1/37 (2.7%)
Flatulence	1/37 (2.7%)
Mucositis oral	5/37 (13.5%)
Nausea	24/37 (64.9%)
Oral pain	7/37 (18.9%)
Rectal pain	1/37 (2.7%)
Small intestinal mucositis	1/37 (2.7%)
Toothache	1/37 (2.7%)
Typhlitis	1/37 (2.7%)
Vomiting	11/37 (29.7%)
General disorders
Chills	6/37 (16.2%)
Edema limbs	6/37 (16.2%)
Edema trunk	4/37 (10.8%)
Facial pain	1/37 (2.7%)
Fatigue	22/37 (59.5%)
Fever	22/37 (59.5%)
Hypothermia	1/37 (2.7%)
Infusion related reaction	5/37 (13.5%)
Non-cardiac chest pain	3/37 (8.1%)
Pain	8/37 (21.6%)
Immune system disorders
Cytokine release syndrome	1/37 (2.7%)
Immune system disorders - Other, specify	1/37 (2.7%)
Infections and infestations
Catheter related infection	3/37 (8.1%)
Enterocolitis infectious	2/37 (5.4%)
Hepatic infection	1/37 (2.7%)
Infections and infestations - Other, specify	4/37 (10.8%)
Lung infection	10/37 (27%)
Mucosal infection	3/37 (8.1%)
Upper respiratory infection	1/37 (2.7%)
Urinary tract infection	2/37 (5.4%)
Vaginal infection	1/37 (2.7%)
Injury, poisoning and procedural complications
Bruising	5/37 (13.5%)
Fall	2/37 (5.4%)
Investigations
Activated partial thromboplastin time prolonged	5/37 (13.5%)
Alanine aminotransferase increased	22/37 (59.5%)
Alkaline phosphatase increased	21/37 (56.8%)
Aspartate aminotransferase increased	23/37 (62.2%)
Blood bilirubin increased	18/37 (48.6%)
Cardiac troponin I increased	3/37 (8.1%)
Creatinine increased	9/37 (24.3%)
Ejection fraction decreased	2/37 (5.4%)
Electrocardiogram QT corrected interval prolonged	3/37 (8.1%)
Haptoglobin decreased	1/37 (2.7%)
INR increased	1/37 (2.7%)
Investigations - Other, specify	8/37 (21.6%)
Lipase increased	1/37 (2.7%)
Lymphocyte count decreased	30/37 (81.1%)
Lymphocyte count increased	1/37 (2.7%)
Neutrophil count decreased	29/37 (78.4%)
Platelet count decreased	34/37 (91.9%)
Weight gain	2/37 (5.4%)
Weight loss	1/37 (2.7%)
White blood cell decreased	34/37 (91.9%)
Metabolism and nutrition disorders
Acidosis	1/37 (2.7%)
Alkalosis	1/37 (2.7%)
Anorexia	11/37 (29.7%)
Dehydration	1/37 (2.7%)
Hypercalcemia	3/37 (8.1%)
Hyperglycemia	7/37 (18.9%)
Hyperkalemia	5/37 (13.5%)
Hypermagnesemia	10/37 (27%)
Hypernatremia	4/37 (10.8%)
Hyperuricemia	4/37 (10.8%)
Hypoalbuminemia	31/37 (83.8%)
Hypocalcemia	29/37 (78.4%)
Hypokalemia	29/37 (78.4%)
Hypomagnesemia	19/37 (51.4%)
Hyponatremia	18/37 (48.6%)
Hypophosphatemia	8/37 (21.6%)
Obesity	1/37 (2.7%)
Tumor lysis syndrome	2/37 (5.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	6/37 (16.2%)
Back pain	7/37 (18.9%)
Bone pain	6/37 (16.2%)
Generalized muscle weakness	4/37 (10.8%)
Joint range of motion decreased	1/37 (2.7%)
Muscle weakness right-sided	1/37 (2.7%)
Musculoskeletal and connective tissue disorder - Other, specify	1/37 (2.7%)
Myalgia	6/37 (16.2%)
Neck pain	1/37 (2.7%)
Pain in extremity	7/37 (18.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	1/37 (2.7%)
Nervous system disorders
Ataxia	1/37 (2.7%)
Dizziness	8/37 (21.6%)
Dysarthria	3/37 (8.1%)
Dysgeusia	7/37 (18.9%)
Headache	21/37 (56.8%)
Memory impairment	1/37 (2.7%)
Nystagmus	1/37 (2.7%)
Paresthesia	2/37 (5.4%)
Sinus pain	2/37 (5.4%)
Somnolence	3/37 (8.1%)
Syncope	1/37 (2.7%)
Tremor	1/37 (2.7%)
Psychiatric disorders
Anxiety	1/37 (2.7%)
Confusion	1/37 (2.7%)
Insomnia	6/37 (16.2%)
Renal and urinary disorders
Acute kidney injury	2/37 (5.4%)
Hematuria	10/37 (27%)
Proteinuria	7/37 (18.9%)
Reproductive system and breast disorders
Genital edema	2/37 (5.4%)
Menorrhagia	2/37 (5.4%)
Prostatic pain	1/37 (2.7%)
Reproductive system and breast disorders - Other, specify	1/37 (2.7%)
Scrotal pain	2/37 (5.4%)
Testicular disorder	1/37 (2.7%)
Uterine hemorrhage	1/37 (2.7%)
Uterine pain	1/37 (2.7%)
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage	1/37 (2.7%)
Cough	11/37 (29.7%)
Dyspnea	8/37 (21.6%)
Epistaxis	9/37 (24.3%)
Hiccups	1/37 (2.7%)
Hypoxia	2/37 (5.4%)
Nasal congestion	5/37 (13.5%)
Pleural effusion	4/37 (10.8%)
Pneumothorax	2/37 (5.4%)
Pulmonary edema	5/37 (13.5%)
Pulmonary hypertension	1/37 (2.7%)
Respiratory, thoracic and mediastinal disorders - Other, specify	1/37 (2.7%)
Sleep apnea	1/37 (2.7%)
Sore throat	2/37 (5.4%)
Wheezing	1/37 (2.7%)
Skin and subcutaneous tissue disorders
Alopecia	3/37 (8.1%)
Dry skin	4/37 (10.8%)
Nail ridging	1/37 (2.7%)
Pruritus	16/37 (43.2%)
Purpura	2/37 (5.4%)
Rash maculo-papular	18/37 (48.6%)
Skin and subcutaneous tissue disorders - Other, specify	4/37 (10.8%)
Skin ulceration	1/37 (2.7%)
Vascular disorders
Hypertension	5/37 (13.5%)
Hypotension	9/37 (24.3%)
Thromboembolic event	1/37 (2.7%)
Vascular disorders - Other, specify	1/37 (2.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.