Avelumab 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: NCT02953561
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 19
• Location: 1
• Arm: 1
• Actual Duration (Months): 31.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This phase Ib/II trial studies the best dose and side effects of avelumab when given together with azacitidine and to see how well they work in treating patients with acute myeloid leukemia that is not responding to treatment or has come back. Monoclonal antibodies, such as avelumab, may interfere with the ability of cancer cells to grow and spread. Azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving avelumab and azacitidine may work better in treating patients with acute myeloid leukemia.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia	Drug: Avelumab; Drug: Azacitidine; Other: Laboratory Biomarker Analysis	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of avelumab in combination with azacitidine (5-azacytidine) in patients with refractory/relapsed acute myeloid leukemia (AML). (Phase IB)

2. To determine the overall response rate (ORR) defined as complete remission (CR)/complete remission with incomplete platelet recovery (CRp)/complete remission with incomplete count recovery (CRi)/partial remission (PR)/hematologic improvement (HI)/morphologic leukemia free state (MLFS) of avelumab in combination with 5-azacytidine in patients with refractory/relapsed AML. (Phase II

SECONDARY OBJECTIVES:

1. To determine the number of patients achieve > 50% reduction in blasts on therapy with this combination.

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

TERTIARY OBJECTIVES:

1. To study immunological and molecular features at baseline and at predefined time-points on-therapy with avelumab and azacytidine in the peripheral blood and bone marrow to include quantify immune ligand expression by the AML blasts and AML stromal components (myeloid-derived suppressor cells [MDSCs] and mesenchymal stem cells [MSCs]) including 4-1BBL, ICOSL, PD-L1, PD-L2, OX-40L, CD137L.

2. To study immunological and molecular features at baseline and at predefined time-points on-therapy with avelumab and azacytidine in the peripheral blood and bone marrow to determine the quantitative expression of positive and negative co-stimulatory molecules on individual T-lymphocyte subsets including 4-1BB, CTLA-4, ICOS, PD-1, OX40, LAG-3 and TIM-3.

3. To study immunological and molecular features at baseline and at predefined time-points on-therapy with avelumab and azacytidine in the peripheral blood and bone marrow to identify the immunophenotype of tumor-infiltrating T-lymphocytes (TILs) pre- and post-therapy with the combination: CD8+, CD4+ effector, or CD4+ regulatory.

4. To develop a micro-array based gene expression profile (GEP) predictor of response to anti-PDL1 and epigenetic therapy in AML.

5. To determine the correlation of responses to the combination with baseline cytogenetic and molecular abnormalities

OUTLINE: This is a phase Ib, dose-escalation study of avelumab followed by a phase II study

Patients receive azacitidine subcutaneously (SC) or intravenously (IV) over 10-40 minutes on days 1-7 or on days 1-5 and 8-9. Patients also receive avelumab IV over 60 minutes on days 1 and 14 for 4 courses (or until complete response) and on day 1 for subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity

After completion of study treatment, patients are followed up every 3-6 months for up to 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Phase Ib/II Study of Avelumab in Combination With 5-Azacytidine (Vidaza) for the Treatment of Patients With Refractory/Relapsed Acute Myeloid Leukemia
• Actual Study Start Date: Feb 20, 2017
• Actual Primary Completion Date: Sep 30, 2019
• Actual Study Completion Date: Sep 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (azacitidine, avelumab) Patients receive azacitidine SC or IV over 10-40 minutes on days 1-7 or on days 1-5 and 8-9. Patients also receive avelumab IV over 60 minutes on days 1 and 14 for 4 courses (or until complete response) and on day 1 for subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Avelumab; Given IV; Other Names: Bavencio MSB-0010718C MSB0010718C ; Drug: Azacitidine; Given SC or IV; Other Names: 5 AZC 5-AC 5-Azacytidine 5-AZC Azacytidine Azacytidine, 5- Ladakamycin Mylosar U-18496 Vidaza ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Number of Participants With a Response [Up to 2 years]

   Complete Response (CR) + Partial Remission (PR) + Complete Remission with incomplete recovery (CRi) + Clinical Benefit. CR = normalization of peripheral blood (PB) and bone marrow (BM) with </= 5% BM blasts, PB granulocyte count >/= (1.0 x 10^9/L, and a platelet count >/= 100 x 10^9/L). PR = same as CR except presence of 6-15% marrow blasts, or 50% reduction if <15% at start of treatment. CRi meets all criteria for CR except for platelet recovery to >100 x 10^9/L and/or granulocyte count > (1.0 x 10^9/L). MLFS is BM with </= 5% BM blasts with no PB recovery. Hematologic Improvement is platelets increase by >/= 30 x 10^9/L untransfused (if <20 at pretherapy); or granulocytes increase by 100% and to >0.5 x 10^9/L (if lower than that pre-therapy); or hemoglobin increase by 2 g/dl; or transfusion independent; or splenomegaly reduction by > 50%; or monocytosis reduction by > 50% if pretreatment > 5 x 109/L, or BM or PB Blasts decrease by >/= 50%.

Secondary Outcome Measures

1. Disease-free Survival [Up to 1 year]

   Time from date of treatment start until the date of first objective documentation of disease-relapse.

2. Overall Survival (OS) [Up to 1 year]

   Distribution of OS will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.

3. Progression Free Survival (PFS) [Up to 1 year]

   Distribution of PFS will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.

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 who are refractory (up to salvage 2) or relapsed (up to 2nd relapse); for patients with prior myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) or myeloproliferative neoplasm (MPN) who transformed to AML, therapy received for MDS, CMML, or MPN is NOT considered as prior therapy 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 =< 1.5 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)

• Estimated creatinine clearance >= 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)

• 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 avelumab will be at least 14 days OR at least 5 half-lives for cytotoxic/noncytotoxic agents, whichever is longer; the toxicity from prior therapy should have resolved to grade =< 1, however alopecia and sensory neuropathy grade =< 2 is acceptable; the half-life for the therapy in question will be based on published pharmacokinetic literature (abstracts, manuscripts, investigator brochures, or drug-administration manuals) and will be documented in the protocol eligibility document; use of hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and will not require a washout; concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted; patients with CNS disease or leukemic brain metastasis must have been treated locally and be clinically stable for at least 2 weeks prior to enrollment and have no ongoing neurological symptoms that are related to the CNS disease (sequelae that are a consequence of the treatment of the CNS disease are acceptable)

• 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 3 months after the last treatment; males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment; adequate methods of contraception include:

• Total abstinence when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception

• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment

• Male sterilization (at least 6 months prior to screening); for female patients on the study, the vasectomized male partner should be the sole partner for that patient

• Combination of any of the two following (a+b or a+c or b+c)

• 1. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception
• 1. Placement of an intrauterine device (IUD) or intrauterine system (IUS)
• 1. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository In case of use of oral contraception, women should have been stable on the same pill before taking study treatment

• Note: oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction

• 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 a known allergy or hypersensitivity to avelumab, 5-azacytidine, or any of their components; known severe hypersensitivity reactions to monoclonal antibodies (grade >= 3 National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4.03), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)

• Patients with a known history of severe interstitial lung disease or severe pneumonitis or active pneumonitis/pneumonia or pulmonary pathology that is not well controlled in the opinion of the treating physician and/or principal investigator (PI)

• Patients who have previously been treated with avelumab (or another PD1/PDL1 inhibitor) in combination with 5-azacytidine will be excluded

• Persisting toxicity related to prior therapy of grade > 1 NCI-CTCAE v 4.03; however, alopecia and sensory neuropathy grade =< 2 is acceptable

• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent: a) subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible; b) subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses =< 10 mg or 10 mg equivalent prednisone per day; c) administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable

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

• Patients who are < 90 days post allogeneic stem cell transplant will be excluded; patients beyond 90 days post-allogeneic stem cell transplant with active uncontrolled graft versus host disease (GVHD) > grade 1 will be excluded; patients who are on a stable dose of immunosuppressive therapy (tacrolimus, cyclosporine, or other) for > 2 weeks will be eligible but those with recent increase in the immunosuppressive medication dose within last 2 weeks to control GVHD will not be included; Note: subjects may be using systemic corticosteroids or topical or inhaled corticosteroids post allogeneic stem cell transplant; patients requiring >= 1 mg/kg prednisone for GVHD management at the time of screening will not be eligible until the prednisone can be weaned to < 1 mg/kg; such patients should be monitored for at least 14 days and if no flare of GVHD requiring re-escalation of steroids or additional interventions for the GVHD they will be eligible

• 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 known human immunodeficiency virus seropositivity will be excluded

• 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

• All other significant diseases (for example, inflammatory bowel disease, uncontrolled asthma), which, in the opinion of the investigator, might impair the subject's tolerance of trial treatment

• Patients unwilling or unable to comply with the protocol

• Pregnant or breastfeeding

• Known alcohol or drug abuse within the last 1 year

• Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines

• Acute promyelocytic leukemia (APL)

• Subject has a history of other malignancies prior to study entry, with the exception of: adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; previous malignancy confirmed and surgically resected (or treated with other modalities) with curative intent or completed definitive therapy (chemotherapy, radiation, others) for the malignancy at least 1 year prior to the date of screening

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 - Jul 26, 2018

More Information

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT02953561
• Other Study ID Numbers: 2016-0444; NCI-2016-01924; 2016-0444; P30CA016672
• First Posted: Nov 2, 2016
• Last Update Posted: Oct 22, 2020
• Last Verified: Sep 1, 2020

• 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; Myelodysplastic Syndromes; Azacitidine; Avelumab; Antibodies, Monoclonal

Study Results

Participant Flow

Recruitment Details	Recruitment Period: February 2017 to February 2019

Arm/Group Title	Treatment (Azacitidine, Avelumab)
Arm/Group Description	Patients receive azacitidine SC or IV over 10-40 minutes on days 1-7 or on days 1-5 and 8-9. Patients also receive avelumab IV over 60 minutes on days 1 and 14 for 4 courses (or until complete response) and on day 1 for subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Avelumab: Given IV Azacitidine: Given subcutaneous or IV Laboratory Biomarker Analysis: Correlative studies
Period Title: Overall Study
STARTED	19
COMPLETED	19
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Azacitidine, Avelumab)
Arm/Group Description	Patients receive azacitidine SC or IV over 10-40 minutes on days 1-7 or on days 1-5 and 8-9. Patients also receive avelumab IV over 60 minutes on days 1 and 14 for 4 courses (or until complete response) and on day 1 for subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Avelumab: Given IV Azacitidine: Given SC or IV Laboratory Biomarker Analysis: Correlative studies
Overall Participants	19
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	8 42.1%
>=65 years	11 57.9%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	69
Sex: Female, Male (Count of Participants)
Female	9 47.4%
Male	10 52.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 15.8%
White	15 78.9%
More than one race	0 0%
Unknown or Not Reported	1 5.3%
Region of Enrollment (participants) [Number]
United States	19 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Response
Description	Complete Response (CR) + Partial Remission (PR) + Complete Remission with incomplete recovery (CRi) + Clinical Benefit. CR = normalization of peripheral blood (PB) and bone marrow (BM) with </= 5% BM blasts, PB granulocyte count >/= (1.0 x 10^9/L, and a platelet count >/= 100 x 10^9/L). PR = same as CR except presence of 6-15% marrow blasts, or 50% reduction if <15% at start of treatment. CRi meets all criteria for CR except for platelet recovery to >100 x 10^9/L and/or granulocyte count > (1.0 x 10^9/L). MLFS is BM with </= 5% BM blasts with no PB recovery. Hematologic Improvement is platelets increase by >/= 30 x 10^9/L untransfused (if <20 at pretherapy); or granulocytes increase by 100% and to >0.5 x 10^9/L (if lower than that pre-therapy); or hemoglobin increase by 2 g/dl; or transfusion independent; or splenomegaly reduction by > 50%; or monocytosis reduction by > 50% if pretreatment > 5 x 109/L, or BM or PB Blasts decrease by >/= 50%.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Of the 19 participants registered, 17 participants were evaluable for response.

Arm/Group Title	Treatment (Azacitidine, Avelumab)
Arm/Group Description	Patients receive azacitidine SC or IV over 10-40 minutes on days 1-7 or on days 1-5 and 8-9. Patients also receive avelumab IV over 60 minutes on days 1 and 14 for 4 courses (or until complete response) and on day 1 for subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Avelumab: Given IV Azacitidine: Given SC or IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	17
Count of Participants [Participants]	4 21.1%

2. Secondary Outcome

Title	Disease-free Survival
Description	Time from date of treatment start until the date of first objective documentation of disease-relapse.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Azacitidine, Avelumab)
Arm/Group Description	Patients receive azacitidine SC or IV over 10-40 minutes on days 1-7 or on days 1-5 and 8-9. Patients also receive avelumab IV over 60 minutes on days 1 and 14 for 4 courses (or until complete response) and on day 1 for subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Avelumab: Given IV Azacitidine: Given SC or IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	17
Median (Full Range) [Months]	8.2

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Distribution of OS will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Azacitidine, Avelumab)
Arm/Group Description	Patients receive azacitidine SC or IV over 10-40 minutes on days 1-7 or on days 1-5 and 8-9. Patients also receive avelumab IV over 60 minutes on days 1 and 14 for 4 courses (or until complete response) and on day 1 for subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Avelumab: Given IV Azacitidine: Given SC or IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	17
Median (Full Range) [Months]	4.7

4. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Distribution of PFS will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Azacitidine, Avelumab)
Arm/Group Description	Patients receive azacitidine SC or IV over 10-40 minutes on days 1-7 or on days 1-5 and 8-9. Patients also receive avelumab IV over 60 minutes on days 1 and 14 for 4 courses (or until complete response) and on day 1 for subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Avelumab: Given IV Azacitidine: Given SC or IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	17
Median (Full Range) [Months]	3.2

Adverse Events

Time Frame	Up to 1 year
Arm/Group Title	Treatment (Azacitidine, Avelumab)
Arm/Group Description	Patients receive azacitidine SC or IV over 10-40 minutes on days 1-7 or on days 1-5 and 8-9. Patients also receive avelumab IV over 60 minutes on days 1 and 14 for 4 courses (or until complete response) and on day 1 for subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Avelumab: Given IV Azacitidine: Given SC or IV Laboratory Biomarker Analysis: Correlative studies
All Cause Mortality
	Treatment (Azacitidine, Avelumab)
	Affected / at Risk (%)	# Events
Total	5/19 (26.3%)
Serious Adverse Events
	Treatment (Azacitidine, Avelumab)
	Affected / at Risk (%)	# Events
Total	18/19 (94.7%)
Blood and lymphatic system disorders
Blood and Lymphatic System Disorders	1/19 (5.3%)	1
Gastrointestinal disorders
Diarrhea	1/19 (5.3%)	1
Dysphagia	1/19 (5.3%)	1
Gastrointestinal disorders	1/19 (5.3%)	1
General disorders
Death	1/19 (5.3%)	1
Fever	1/19 (5.3%)	1
Pain	1/19 (5.3%)	1
Infections and infestations
Anorectal Infection	2/19 (10.5%)	3
Endocarditis	1/19 (5.3%)	1
Neutropenic Fever	4/19 (21.1%)	4
Infection	3/19 (15.8%)	6
Lung Infection	6/19 (31.6%)	12
Pneumonitis	3/19 (15.8%)	3
Sepsis	3/19 (15.8%)	4
Skin Infection	1/19 (5.3%)	1
Soft Tissue Infection	1/19 (5.3%)	1
Metabolism and nutrition disorders
Hyponatremia	1/19 (5.3%)	1
Metabolism and Nutrition Disorder	1/19 (5.3%)	1
Nervous system disorders
Stroke	1/19 (5.3%)	1
Syncope	1/19 (5.3%)	1
Renal and urinary disorders
Hematuria	1/19 (5.3%)	1
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	1/19 (5.3%)	2
Vascular disorders
Hypotension	1/19 (5.3%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Azacitidine, Avelumab)
	Affected / at Risk (%)	# Events
Total	16/19 (84.2%)
Blood and lymphatic system disorders
Anemia	2/19 (10.5%)	2
Blood and Lymphatic System Disorders	1/19 (5.3%)	1
Neutropenic Fever	1/19 (5.3%)	1
Endocrine disorders
Hypothyroidism	1/19 (5.3%)	1
Gastrointestinal disorders
Anorexia	3/19 (15.8%)	3
Diarrhea	6/19 (31.6%)	6
Oral Mucositis	4/19 (21.1%)	4
Nausea	6/19 (31.6%)	6
Vomiting	7/19 (36.8%)	8
General disorders
Cbills	1/19 (5.3%)	1
Fatigue	4/19 (21.1%)	4
Infusion Related Reaction	4/19 (21.1%)	5
Infections and infestations
Alkaline Phosphatase Increased	1/19 (5.3%)	1
Mucosal Infection	1/19 (5.3%)	1
Investigations
Elevated Alanine Aminotransferase Increase	2/19 (10.5%)	2
Blood Bilirubin Increased	1/19 (5.3%)	1
Cardiac Troponin I Increase	1/19 (5.3%)	1
Lymphocyte Count Decreased	2/19 (10.5%)	2
Neutropenia	2/19 (10.5%)	2
Platelet Count Decrease	1/19 (5.3%)	1
White Blood Count Decreased	2/19 (10.5%)	3
Metabolism and nutrition disorders
Hyperglycemia	1/19 (5.3%)	1
Hypoalbuminemia	1/19 (5.3%)	1
hyponatremia	1/19 (5.3%)	1
Musculoskeletal and connective tissue disorders
Generalized Muscle Weakness	2/19 (10.5%)	2
Nervous system disorders
Headache	1/19 (5.3%)	1
Psychiatric disorders
Confusion	3/19 (15.8%)	3
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	2/19 (10.5%)	2
Skin and subcutaneous tissue disorders
Rash	2/19 (10.5%)	2
Vascular disorders
Hypertension	2/19 (10.5%)	2

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.