Lirilumab and Azacitidine in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02399917
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 36
• Location: 1
• Arms: 3
• Actual Duration (Months): 38.7
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This phase II trial studies the side effects lirilumab and azacitidine and to see how well they work in treating patients with acute myeloid leukemia that has not responded to treatment or has returned after a period of improvement. Monoclonal antibodies, such as lirilumab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving lirilumab with azacitidine may be an effective treatment for relapsed or refractory acute myeloid leukemia.

Condition or Disease	Intervention/Treatment	Phase
Acute Biphenotypic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia	Drug: Azacitidine; Biological: Lirilumab	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of lirilumab in combination with 5-azacytidine (azacitidine) in patients with refractory/relapsed acute myeloid leukemia (AML). (Part A, Lead-In Phase) II. To determine the overall response rate (ORR) of lirilumab in combination with 5-azacytidine in patients with refractory/relapsed AML. (Part B, Phase II)

SECONDARY OBJECTIVES:

1. To determine the duration of response, disease-free survival (DFS), and overall survival (OS) of patients with refractory/relapsed AML treated with this combination.

2. To determine the safety of lirilumab in combination with 5-azacytidine in patients with refractory/relapsed AML.

OUTLINE:

Patients receive azacitidine subcutaneously (SC) or intravenously (IV) over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and up to 90 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Phase IB, lead-in/II to determine MTDPhase IB, lead-in/II to determine MTD
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Phase II Study of Lirilumab (BMS-986015) in Combination With 5-Azacytidine (Vidaza) for the Treatment of Patients With Refractory/Relapsed Acute Myeloid Leukemia
• Actual Study Start Date: Apr 20, 2015
• Actual Primary Completion Date: Jul 12, 2018
• Actual Study Completion Date: Jul 12, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1b Lead-in Cohort 1 Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 1.0 mg/kg	Drug: Azacitidine; Given SC or IV; Other Names: 5 AZA 5-AC 5-Azacytidine 5-AZC Azacytidine Azacytidine, 5- Ladakamycin Mylosar U-18496 Vidaza ; Biological: Lirilumab; Given IV; Other Names: BMS-986015 IPH2102
Experimental: Phase 1b Lead-in Cohort 2 Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 3.0 mg/kg	Drug: Azacitidine; Given SC or IV; Other Names: 5 AZA 5-AC 5-Azacytidine 5-AZC Azacytidine Azacytidine, 5- Ladakamycin Mylosar U-18496 Vidaza ; Biological: Lirilumab; Given IV; Other Names: BMS-986015 IPH2102
Experimental: Phase 2 Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 3.0 mg/kg	Drug: Azacitidine; Given SC or IV; Other Names: 5 AZA 5-AC 5-Azacytidine 5-AZC Azacytidine Azacytidine, 5- Ladakamycin Mylosar U-18496 Vidaza ; Biological: Lirilumab; Given IV; Other Names: BMS-986015 IPH2102

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose of Iirilumab in Combination With 5-azacitidine [Up to 28 days]

   To identify the dose at which <2/6 participants experience Dose Limiting Toxicities (DLT). The dose level at which 0-1/6 participants experience a DLT in the first 28 days of treatment will be the maximum tolerated dose (MTD) and would be used to treat an additional 34 participants in the phase II potion of the study. (Part A, Lead-In Phase)

2. Participants With an Objective Response [Up to 3 months]

   Objective Response Rate (ORR) will be monitored using the Bayesian approach of Thall, Simon, Estey and the extension by Thall and Sung. Overall response rate (ORR), defined as complete remission (CR) + CR with incomplete platelet recovery (CRp) + CR with incomplete count recovery (CRi) + partial response (PR) + marrow clearance of blasts + hematological improvement within 3 months of treatment initiation among adult patients with refractory/relapsed Acute Myelogenous Leukemia (AML) (Phase II)

Secondary Outcome Measures

1. Duration of Response [Up to 2.5 years]

   The date of Objective Response to the date of loss of response or last follow-up.

2. Overall Survival [Up to 2 years]

   Overall Survival (OS) is defined: Time of presentation to date of death or censored at last follow-up date.

3. Disease Free Survival [Up to 2.5 years]

   Disease Free Survival (DFS) is defined: Time from date of treatment start until the date of first objective documentation of disease-relapse

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with AML or biphenotypic or bilineage leukemia who have failed at least one prior therapy; patients with AML should have failed prior therapy or have relapsed after prior therapy

• Patients should not be eligible or able to receive approved therapy of confirmed clinical benefit in this patient population

• Patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) who received therapy for the MDS or CMML and progress to AML are eligible at the time of diagnosis of AML regardless any prior therapy for AML; the World Health Organization (WHO) classification will be used for AML

• Prior therapy with hydroxyurea, chemotherapy, biological or targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors), or hematopoietic growth factors is allowed

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2

• Total bilirubin =< 2 times upper limit of normal (x ULN) (=< 3 x ULN if considered to be due to leukemic involvement or Gilbert's syndrome)

• Aspartate aminotransferase or alanine aminotransferase =< 2.5 x ULN (=< 5.0 x ULN if considered to be due to leukemic involvement)

• Serum creatinine =< 2 x ULN or glomerular filtration rate (GFR) >= 50

• Patients must provide written informed consent

• In the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of 5-azacytidine and lirilumab will be at least 2 weeks OR at least 5 half-lives for cytotoxic/noncytotoxic agents; use of one dose of cytarabine (up to 2 g/m^2) is allowed prior to the start of study therapy or hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and while the patient is on active study treatment, as needed, for clinical benefit and after discussion with the principal investigator (PI); concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted

• Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum or urine pregnancy test within 72 hours before the start of the treatment

• Women of childbearing potential must agree to use an adequate method of contraception during the study and until 30 days after the last treatment; males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 30 days after the last treatment; women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential

Exclusion Criteria:

• Patients with known allergy or hypersensitivity to lirilumab, 5-azacytidine, or any of their components; patients who have previously been treated with lirilumab in combination with 5-azacytidine will be excluded

• Patients with a known history of severe interstitial lung disease or severe pneumonitis or active pneumonitis that is uncontrolled in the opinion of the treating physician

• Patients with a known history of any of the following autoimmune diseases are excluded: (a) patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) (b) patients with a history of rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis])

• Patients with organ allografts (such as renal transplant) are excluded

• Patients with allogeneic stem cell transplantation within the last 6 months or patients with active graft-versus-host disease (GVHD) will be excluded

• Ongoing immunosuppressive therapy, including cyclosporine and tacrolimus; patients who are on high dose steroid; Note: Subjects may be using systemic corticosteroids (daily doses =< 10 mg of prednisone or equivalent) or topical or inhaled corticosteroids

• Patients with symptomatic CNS leukemia or patients with poorly controlled CNS leukemia

• Active and uncontrolled disease/(active uncontrolled infection, uncontrolled hypertension despite adequate medical therapy, active and uncontrolled congestive heart failure New York Heart Association [NYHA] class III/IV, clinically significant and uncontrolled arrhythmia) as judged by the treating physician

• Patients with active and uncontrolled human immunodeficiency virus (HIV) infection will be excluded; however, patients with well controlled HIV infection will be considered

• Patients known to be positive for hepatitis B by surface antigen expression; known to have active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months)

• Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator

• Patients unwilling or unable to comply with the protocol

• Pregnant or breastfeeding

• Acute promyelocytic leukemia (APL)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Naval Daver, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 3, 2018

More Information

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT02399917
• Other Study ID Numbers: 2014-0862; NCI-2015-00678; 2014-0862; P30CA016672
• First Posted: Mar 26, 2015
• Last Update Posted: Sep 24, 2019
• Last Verified: Sep 1, 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; Leukemia, Biphenotypic, Acute; Myelodysplastic Syndromes; Azacitidine

Study Results

Participant Flow

Recruitment Details	Recruitment Period: May 2015 - June 2017

Arm/Group Title	Phase 1b Lead-in Cohort 1	Phase 1b Lead-in Cohort 2	Phase 2
Arm/Group Description	Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 1.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV	Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 3.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV	Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 3.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV
Period Title: Overall Study
STARTED	6	6	24
COMPLETED	6	6	24
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Phase 1b Lead-in Cohort 1	Phase 1b Lead-in Cohort 2	Phase 2	Total
Arm/Group Description	Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 1.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV	Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 3.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV	Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 3.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV	Total of all reporting groups
Overall Participants	6	6	24	36
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	4 66.7%	3 50%	13 54.2%	20 55.6%
>=65 years	2 33.3%	3 50%	11 45.8%	16 44.4%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59.5	68.5	65	64
Sex: Female, Male (Count of Participants)
Female	1 16.7%	3 50%	14 58.3%	18 50%
Male	5 83.3%	3 50%	10 41.7%	18 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	1 16.7%	0 0%	4 16.7%	5 13.9%
White	5 83.3%	6 100%	19 79.2%	30 83.3%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	1 4.2%	1 2.8%
Region of Enrollment (participants) [Number]
United States	6 100%	6 100%	24 100%	36 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose of Iirilumab in Combination With 5-azacitidine
Description	To identify the dose at which <2/6 participants experience Dose Limiting Toxicities (DLT). The dose level at which 0-1/6 participants experience a DLT in the first 28 days of treatment will be the maximum tolerated dose (MTD) and would be used to treat an additional 34 participants in the phase II potion of the study. (Part A, Lead-In Phase)
Time Frame	Up to 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Phase 1 Participants
Arm/Group Description	Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 1.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV
Measure Participants	12
Number [mg/kg]	3.0

2. Primary Outcome

Title	Participants With an Objective Response
Description	Objective Response Rate (ORR) will be monitored using the Bayesian approach of Thall, Simon, Estey and the extension by Thall and Sung. Overall response rate (ORR), defined as complete remission (CR) + CR with incomplete platelet recovery (CRp) + CR with incomplete count recovery (CRi) + partial response (PR) + marrow clearance of blasts + hematological improvement within 3 months of treatment initiation among adult patients with refractory/relapsed Acute Myelogenous Leukemia (AML) (Phase II)
Time Frame	Up to 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 1b Lead-in Cohort 1	Phase 1b Lead-in Cohort 2	Phase 2
Arm/Group Description	Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 1.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV	Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 3.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV	Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 3.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV
Measure Participants	6	6	24
Count of Participants [Participants]	2 33.3%	1 16.7%	2 8.3%

3. Secondary Outcome

Title	Duration of Response
Description	The date of Objective Response to the date of loss of response or last follow-up.
Time Frame	Up to 2.5 years

Outcome Measure Data

Analysis Population Description

The outcome for the secondary response, duration of response was only done on the Phase II portion of this study.

Arm/Group Title	Phase 1b Lead-in Cohort 1	Phase 1b Lead-in Cohort 2	Phase 2
Arm/Group Description	Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 1.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV	Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 3.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV	Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 3.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV
Measure Participants	0	0	24
Median (Full Range) [Months]	7.7

4. Secondary Outcome

Title	Overall Survival
Description	Overall Survival (OS) is defined: Time of presentation to date of death or censored at last follow-up date.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

The outcome for the secondary response, overall response was only done on the Phase II portion of this study.

Arm/Group Title	Phase 1b Lead-in Cohort 1	Phase 1b Lead-in Cohort 2	Phase 2
Arm/Group Description	Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 1.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV	Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 3.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV	Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 3.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV
Measure Participants	0	0	24
Median (Full Range) [Months]	3.5

5. Secondary Outcome

Title	Disease Free Survival
Description	Disease Free Survival (DFS) is defined: Time from date of treatment start until the date of first objective documentation of disease-relapse
Time Frame	Up to 2.5 years

Outcome Measure Data

Analysis Population Description

The outcome for the secondary response, disease free survival was only done on the Phase II portion of this study.

Arm/Group Title	Phase 1b Lead-in Cohort 1	Phase 1b Lead-in Cohort 2	Phase 2
Arm/Group Description	Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 1.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV	Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 3.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV	Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 3.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV
Measure Participants	0	0	24
Median (Full Range) [Months]	7.7

Adverse Events

Time Frame	Up to two and a half years.
Arm/Group Title	Phase 1b Lead-in Cohort 1		Phase 1b Lead-in Cohort 2		Phase 2
Arm/Group Description	Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 1.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV		Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 3.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV		Patients receive azacitidine SC or IV over 1 hour as determined by the treating physician on days 1-7 and lirilumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. 5-Azacitidine 75mg/m^2 Lirilumab 3.0 mg/kg Azacitidine: Given SC or IV Lirilumab: Given IV
All Cause Mortality
	Phase 1b Lead-in Cohort 1		Phase 1b Lead-in Cohort 2		Phase 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/6 (66.7%)		2/6 (33.3%)		9/24 (37.5%)
Serious Adverse Events
	Phase 1b Lead-in Cohort 1		Phase 1b Lead-in Cohort 2		Phase 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		6/6 (100%)		20/24 (83.3%)
Blood and lymphatic system disorders
Blood and Lymphatic system disorders	3/6 (50%)	3	0/6 (0%)	0	0/24 (0%)	0
Gastrointestinal disorders
Abdominal Distension	1/6 (16.7%)	1	0/6 (0%)	0	0/24 (0%)	0
Abdominal Pain	0/6 (0%)	0	0/6 (0%)	0	2/24 (8.3%)	3
Constipation	0/6 (0%)	0	1/6 (16.7%)	1	0/24 (0%)	0
Gastrointestinal Disorders Other	0/6 (0%)	0	0/6 (0%)	0	1/24 (4.2%)	2
Ileal Perforation	0/6 (0%)	0	0/6 (0%)	0	1/24 (4.2%)	1
Mucositis	0/6 (0%)	0	0/6 (0%)	0	1/24 (4.2%)	1
General disorders
Fatigue	0/6 (0%)	0	0/6 (0%)	0	1/24 (4.2%)	1
Fever	0/6 (0%)	0	0/6 (0%)	0	1/24 (4.2%)	1
Multi-Organ Failure	0/6 (0%)	0	0/6 (0%)	0	1/24 (4.2%)	1
Pain	1/6 (16.7%)	1	0/6 (0%)	0	1/24 (4.2%)	1
Infections and infestations
Neutropenic Fever	2/6 (33.3%)	3	2/6 (33.3%)	3	9/24 (37.5%)	19
Infection	2/6 (33.3%)	2	2/6 (33.3%)	2	4/24 (16.7%)	8
Joint Infection	0/6 (0%)	0	0/6 (0%)	0	1/24 (4.2%)	1
Lung Infection	4/6 (66.7%)	5	0/6 (0%)	0	10/24 (41.7%)	16
Scrotal Infection	0/6 (0%)	0	0/6 (0%)	0	1/24 (4.2%)	1
Sepsis	0/6 (0%)	0	0/6 (0%)	0	3/24 (12.5%)	4
Skin Infection	1/6 (16.7%)	2	0/6 (0%)	0	0/24 (0%)	0
Injury, poisoning and procedural complications
Spinal Fracture	0/6 (0%)	0	1/6 (16.7%)	1	0/24 (0%)	0
Metabolism and nutrition disorders
Hypernatremia	0/6 (0%)	0	0/6 (0%)	0	1/24 (4.2%)	1
Hypokalemia	0/6 (0%)	0	0/6 (0%)	0	1/24 (4.2%)	1
Nervous system disorders
Dizziness	0/6 (0%)	0	0/6 (0%)	0	1/24 (4.2%)	1
Renal and urinary disorders
Hematuria	1/6 (16.7%)	1	0/6 (0%)	0	0/24 (0%)	0
Urinary Tract Infection	1/6 (16.7%)	2	1/6 (16.7%)	1	0/24 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/6 (16.7%)	1	0/6 (0%)	0	0/24 (0%)	0
Respiratory Failure	0/6 (0%)	0	0/6 (0%)	0	2/24 (8.3%)	2
Respiratory other	1/6 (16.7%)	1	0/6 (0%)	0	1/24 (4.2%)	1
Surgical and medical procedures
Surgical/medical procedures other	1/6 (16.7%)	1	0/6 (0%)	0	0/24 (0%)	0
Vascular disorders
Hypotension	0/6 (0%)	0	1/6 (16.7%)	1	2/24 (8.3%)	2
Other (Not Including Serious) Adverse Events
	Phase 1b Lead-in Cohort 1		Phase 1b Lead-in Cohort 2		Phase 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		6/6 (100%)		22/24 (91.7%)
Cardiac disorders
Atrial Fibrillation	1/6 (16.7%)	1	0/6 (0%)	0	2/24 (8.3%)	2
Pericardial Effusion	0/6 (0%)	0	0/6 (0%)	0	5/24 (20.8%)	5
Sinus Bradycardia	1/6 (16.7%)	1	0/6 (0%)	0	6/24 (25%)	7
Gastrointestinal disorders
Abdominal Distension	2/6 (33.3%)	2	0/6 (0%)	0	1/24 (4.2%)	1
Constipation	1/6 (16.7%)	2	1/6 (16.7%)	1	10/24 (41.7%)	12
Diarrhea	2/6 (33.3%)	2	0/6 (0%)	0	8/24 (33.3%)	8
Mucositis	0/6 (0%)	0	0/6 (0%)	0	2/24 (8.3%)	2
Nausea	0/6 (0%)	0	0/6 (0%)	0	3/24 (12.5%)	4
General disorders
Edema	1/6 (16.7%)	1	1/6 (16.7%)	1	4/24 (16.7%)	4
Fever	3/6 (50%)	3	0/6 (0%)	0	8/24 (33.3%)	9
Headache	2/6 (33.3%)	2	0/6 (0%)	0	3/24 (12.5%)	3
Infusion Reaction	1/6 (16.7%)	1	1/6 (16.7%)	1	7/24 (29.2%)	11
Pain	1/6 (16.7%)	1	2/6 (33.3%)	4	10/24 (41.7%)	16
Weight Loss	1/6 (16.7%)	1	0/6 (0%)	0	1/24 (4.2%)	1
Fatigue	1/6 (16.7%)	1	0/6 (0%)	0	0/24 (0%)	0
Infections and infestations
Infection	2/6 (33.3%)	2	0/6 (0%)	0	7/24 (29.2%)	8
Neutropenic Fever	3/6 (50%)	3	0/6 (0%)	0	6/24 (25%)	6
Pneumonia	3/6 (50%)	5	2/6 (33.3%)	2	4/24 (16.7%)	4
Sinusitis	0/6 (0%)	0	1/6 (16.7%)	1	3/24 (12.5%)	3
Urinary Tract Infection	1/6 (16.7%)	1	1/6 (16.7%)	1	7/24 (29.2%)	9
Injury, poisoning and procedural complications
Fall	0/6 (0%)	0	0/6 (0%)	0	5/24 (20.8%)	5
Investigations
Elevated Alanine Aminotransferase increased	0/6 (0%)	0	1/6 (16.7%)	1	2/24 (8.3%)	2
Aspartate Aminotransferase Increased	2/6 (33.3%)	2	3/6 (50%)	3	4/24 (16.7%)	4
Hyperbilirubinemia	1/6 (16.7%)	1	1/6 (16.7%)	1	5/24 (20.8%)	5
Metabolism and nutrition disorders
Anorexia	0/6 (0%)	0	0/6 (0%)	0	3/24 (12.5%)	3
Hyperglycemia	2/6 (33.3%)	2	0/6 (0%)	0	0/24 (0%)	0
Hypocalcemia	1/6 (16.7%)	1	0/6 (0%)	0	1/24 (4.2%)	1
Hypokalemia	1/6 (16.7%)	1	3/6 (50%)	3	3/24 (12.5%)	3
Hypomagnesmia	1/6 (16.7%)	1	0/6 (0%)	0	0/24 (0%)	0
Hyponatremia	0/6 (0%)	0	1/6 (16.7%)	1	3/24 (12.5%)	3
Hypophosphatemia	0/6 (0%)	0	0/6 (0%)	0	3/24 (12.5%)	3
Musculoskeletal and connective tissue disorders
Myalgia	1/6 (16.7%)	1	0/6 (0%)	0	2/24 (8.3%)	3
Nervous system disorders
Peripheral Sensory Neuropathy	0/6 (0%)	0	1/6 (16.7%)	1	0/24 (0%)	0
Psychiatric disorders
Insomnia	1/6 (16.7%)	1	0/6 (0%)	0	4/24 (16.7%)	4
Renal and urinary disorders
Acute Kidney Injury	0/6 (0%)	0	3/6 (50%)	3	0/24 (0%)	0
Hematuria	0/6 (0%)	0	0/6 (0%)	0	4/24 (16.7%)	4
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/6 (0%)	0	0/6 (0%)	0	3/24 (12.5%)	3
Pleural Effusion	0/6 (0%)	0	0/6 (0%)	0	7/24 (29.2%)	7
Respiratory Failure	0/6 (0%)	0	0/6 (0%)	0	4/24 (16.7%)	4
Skin and subcutaneous tissue disorders
Bruising	0/6 (0%)	0	1/6 (16.7%)	1	2/24 (8.3%)	3
Pruritis	0/6 (0%)	0	0/6 (0%)	0	2/24 (8.3%)	2
Rash	2/6 (33.3%)	2	0/6 (0%)	0	2/24 (8.3%)	2
Vascular disorders
Hypertension	1/6 (16.7%)	1	0/6 (0%)	0	2/24 (8.3%)	2
Hypotension	1/6 (16.7%)	2	0/6 (0%)	0	8/24 (33.3%)	8

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.