Decitabine and Midostaurin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

• Sponsor: David Iberri (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01846624
• Collaborator: (none)
• Enrollment: 13
• Location: 1
• Arm: 1
• Duration (Months): 39
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This phase 2 study evaluates the sequential combination of decitabine then midostaurin for the treatment of newly-diagnosed acute myeloid leukemia (AML) in older patients.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia (AML) With Multilineage Dysplasia Following Myelodysplastic Syndrome, in Adults; AML (Adult) With 11q23 (MLL) Abnormalities; AML (Adult) With Del (5q); AML (Adult) With Inv (16) (p13; q22); AML (Adult) With t (16;16) (p13; q22); AML (Adult) With t (8; 21) (q22; q22); Secondary AML (Adult); Untreated AML (Adult)	Drug: Decitabine; Drug: Midostaurin	Phase 2

Detailed Description

Treatment with decitabine, a cytidine analog, then midostaurin, a multi-target protein kinase inhibitor (PKI), may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Decitabine in Combination With Midostaurin (PKC412) for Elderly Patients With Newly Diagnosed FLT3-ITD/TKD Positive Acute Myeloid Leukemia
• Study Start Date: Jun 1, 2013
• Actual Primary Completion Date: Jul 22, 2016
• Actual Study Completion Date: Aug 31, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Decitabine, then midostaurin INDUCTION THERAPY Subjects receive decitabine intravenously (IV) over 1 hour on days 1 to 10 and midostaurin orally (PO) twice daily (BID) on days 11 to 28. Treatment repeats every 28 days until documented bone marrow response is achieved or for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving documented bone marrow response by course 6 continue treatment with induction therapy; patients achieving response after course 6 proceed to post-remission therapy. POST-REMISSION THERAPY Subjects receive decitabine IV over 1 hour on days 1 to 5 and midostaurin PO BID on days 6 to 28. Treatment repeats every 28 days for up to 12 courses (including induction therapy) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for up to 1 year.

Drug: Decitabine; Given IV; Other Names: 5-aza-dCyd 5AZA DAC Dacogen ; Drug: Midostaurin; Given PO; Other Names: N-benzoyl-staurosporine PKC412

Outcome Measures

Primary Outcome Measures

1. Complete Remission (CR) Rate [Up to 1 year]

   The complete remission (CR) rate, or complete response rate, is reported as the sum and proportion of participants that achieved CR or CR with incomplete blood count recovery (CRi), within 12 months of starting midostaurin treatment. Complete remission (CR): Bone marrow blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) > 1000/μL; platelet count > 100,000/μL; independence of red cell transfusions. CR with incomplete recovery (CRi): All CR criteria except for ANC < 1000/μL or platelet count < 100,000/μL. Partial remission (PR): All hematologic criteria of CR; except decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%.

Secondary Outcome Measures

1. Overall Response Rate (ORR) [up to 1 year]

   Overall response rate (ORR) was assessed as the number and proportion of participants who received midostaurin and achieved a partial response (PR), complete response (CR), or complete response with incomplete blood count recovery (CRi). Complete remission (CR): Bone marrow blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) > 1000/μL; platelet count > 100,000/μL; independence of red cell transfusions. CR with incomplete recovery (CRi): All CR criteria except for ANC < 1000/μL or platelet count < 100,000/μL. Partial remission (PR): All hematologic criteria of CR; except decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%.

2. Median Duration of Response (DoR) [Up to 1 year]

   Response was assessed by evaluations conducted every 3 cycles (12 weeks). Once documented as partial response (PR), complete response (CR), or complete response with incomplete blood count recover (CRi), response status was confirmed every 12 weeks. In responding participants, duration of response was assessed from the start of treatment through the last documented response before documented progressive disease or death. The outcome is reported as the median value for duration of response, with full range. CR: Bone marrow blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; ANC > 1000/μL; platelet > 100,000/μL; independence of red cell transfusions. CRi: All CR criteria except ANC < 1000/μL or platelet count < 100,000/μL. PR: All hematologic criteria of CR; except decrease of bone marrow blast percentage to 5% to 25%; & decrease of pretreatment bone marrow blast percentage by at least 50%.

3. Progression-free Survival (PFS) [Up to 2 years]

   Progression-free survival (PFS) is reported as the number and proportion of participants who did not receive hematopoietic cell transplantation, and who did not experience disease progression or death for any reason within 2 years after starting midostaurin treatment. Progressive disease: Bone marrow blasts ≥ 5%; or reappearance of blasts in the blood; or development of extramedullary disease.

4. Overall Survival (OS) [Up to 2 years]

   Survival is reported as the number and proportion of participants that received midostaurin who remained alive 2 years after starting midostaurin treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Newly-diagnosed acute myeloid leukemia (AML) per the World Health Organization [WHO] 2008 classification [except t (15; 17)], including:

• De novo AML

• Secondary AML

• Secondary AML arising from previously-diagnosed myelodysplastic syndromes (MDS) treated with deoxyribonucleic acid (DNA) methyltransferase inhibitor (DNMTi) (ie, decitabine or azacitidine)

• FLT3-ITD mutation confirmed in bone marrow aspirate

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)

• Serum bilirubin ≤ 2.5 ULN

• Serum creatinine ≤ 1.5 mg/dL and/or creatinine clearance ≥ 50 mL/min

• Ejection fraction ≥ 50% by echocardiogram

• Unwillingness or inability to receive conventional chemotherapy

• Ability to understand and the willingness to sign a written informed consent document

• Ability to adhere to the study visit schedule and other protocol requirements

• Life expectancy > 2 months

Exclusion Criteria:

• Receiving concomitant treatment with other anti-neoplastic agents (EXCEPTION: hydroxyurea). Prior treatment with DNMTi therapy (ie, decitabine or azacitidine) for MDS is allowed

• Received anti-neoplastic treatment within 4 weeks prior to enrollment (EXCEPTION: hydroxyurea)

• Received any surgical procedure, excluding central venous catheter placement or other minor procedures (eg, skin biopsy) within 14 days of study day 1

• Received any investigational agent within 4 weeks prior to enrollment

• Previous or current history of a myeloproliferative disease

• Known active central nervous system (CNS) malignancy

• Any other known disease (except carcinoma in-situ), concurrent severe and/or uncontrolled medical condition which could compromise participation in the study (eg, uncontrolled diabetes; cardiovascular disease including congestive heart failure; myocardial infarction within 6 months with poorly controlled hypertension; chronic renal disease; active uncontrolled infection)

• Active opportunistic infection or treatment for opportunistic infection within 4 weeks of first day of study drug dosing

• Known confirmed diagnosis of human immunodeficiency virus (HIV) infection or active viral hepatitis

• Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of midostaurin

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to midostaurin and/or decitabine

• Impaired cardiac function including any of the following:

• Screening electrocardiogram (ECG) with a corrected QT interval (QTc) > 450 msec

• Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm)

• Right bundle branch block + left anterior hemiblock (bifascicular block)

• Patients with myocardial infarction or unstable angina < 3 months prior to starting study drug

• Congestive heart failure (CHF) New York (NY) Heart Association class 3 or 4

• Inability to swallow or absorb drug

• Other medical or psychiatric illness or organ dysfunction or laboratory abnormality which in the opinion of the investigator would compromise the patient's safety or interfere with data interpretation

• Unwillingness or inability to comply with the protocol

• Pregnant

• nursing (lactating)

• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they are using highly effective methods of contraception during dosing and for 3 months after midostaurin medication; highly effective contraception methods as follows:

• Total abstinence, when this is in line with the preferred and usual lifestyle of the subject [periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception]

• Female sterilization (surgical bilateral oophorectomy with or without hysterectomy; or tubal ligation at least six weeks before taking study treatment). In case of oophorectomy alone, reproductive status must be confirmed by follow-up hormone level assessment

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

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

• Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), eg, hormone vaginal ring or transdermal hormone contraception. For oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment

• Placement of an intrauterine device (IUD) or intrauterine system (IUS)

• Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• David Iberri

Investigators

• Principal Investigator: David J Iberri, MD, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Löwenberg B, Bloomfield CD; European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010 Jan 21;115(3):453-74. doi: 10.1182/blood-2009-07-235358. Epub 2009 Oct 30. Review.

• Responsible Party: David Iberri, Clinical Assistant Professor, Stanford University
• ClinicalTrials.gov Identifier: NCT01846624
• Other Study ID Numbers: IRB-25737; HEMAML0022
• First Posted: May 3, 2013
• Last Update Posted: Sep 27, 2018
• Last Verified: Sep 1, 2018

• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Decitabine; Azacitidine; Midostaurin; Staurosporine

Study Results

Participant Flow

Arm/Group Title	Decitabine, Then Midostaurin
Arm/Group Description	INDUCTION THERAPY Subjects receive decitabine intravenously (IV) over 1 hour on days 1 to 10 and midostaurin orally (PO) twice daily (BID) on days 11 to 28. Treatment repeats every 28 days until documented bone marrow response is achieved or for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving documented bone marrow response by course 6 continue treatment with induction therapy; patients achieving response after course 6 proceed to post-remission therapy. POST-REMISSION THERAPY Subjects receive decitabine IV over 1 hour on days 1 to 5 and midostaurin PO BID on days 6 to 28. Treatment repeats every 28 days for up to 12 courses (including induction therapy) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for up to 1 year. Decitabine: Given IV Midostaurin: Given PO
Period Title: Overall Study
STARTED	13
COMPLETED	12
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Decitabine, Then Midostaurin
Arm/Group Description	INDUCTION THERAPY Subjects receive decitabine intravenously (IV) over 1 hour on days 1 to 10 and midostaurin orally (PO) twice daily (BID) on days 11 to 28. Treatment repeats every 28 days until documented bone marrow response is achieved or for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving documented bone marrow response by course 6 continue treatment with induction therapy; patients achieving response after course 6 proceed to post-remission therapy. POST-REMISSION THERAPY Subjects receive decitabine IV over 1 hour on days 1 to 5 and midostaurin PO BID on days 6 to 28. Treatment repeats every 28 days for up to 12 courses (including induction therapy) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for up to 1 year. Decitabine: Given IV Midostaurin: Given PO
Overall Participants	13
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	0 0%
>=65 years	13 100%
Sex: Female, Male (Count of Participants)
Female	6 46.2%
Male	7 53.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 7.7%
Not Hispanic or Latino	12 92.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 7.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	11 84.6%
More than one race	0 0%
Unknown or Not Reported	1 7.7%
Region of Enrollment (participants) [Number]
United States	13 100%

Outcome Measures

1. Primary Outcome

Title	Complete Remission (CR) Rate
Description	The complete remission (CR) rate, or complete response rate, is reported as the sum and proportion of participants that achieved CR or CR with incomplete blood count recovery (CRi), within 12 months of starting midostaurin treatment. Complete remission (CR): Bone marrow blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) > 1000/μL; platelet count > 100,000/μL; independence of red cell transfusions. CR with incomplete recovery (CRi): All CR criteria except for ANC < 1000/μL or platelet count < 100,000/μL. Partial remission (PR): All hematologic criteria of CR; except decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Only participants that started midostaurin therapy are included in the complete response assessment.

Arm/Group Title	Decitabine, Then Midostaurin
Arm/Group Description	INDUCTION THERAPY Subjects receive decitabine intravenously (IV) over 1 hour on days 1 to 10 and midostaurin orally (PO) twice daily (BID) on days 11 to 28. Treatment repeats every 28 days until documented bone marrow response is achieved or for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving documented bone marrow response by course 6 continue treatment with induction therapy; patients achieving response after course 6 proceed to post-remission therapy. POST-REMISSION THERAPY Subjects receive decitabine IV over 1 hour on days 1 to 5 and midostaurin PO BID on days 6 to 28. Treatment repeats every 28 days for up to 12 courses (including induction therapy) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for up to 1 year. Decitabine: Given IV Midostaurin: Given PO
Measure Participants	12
Count of Participants [Participants]	8 61.5%

2. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	Overall response rate (ORR) was assessed as the number and proportion of participants who received midostaurin and achieved a partial response (PR), complete response (CR), or complete response with incomplete blood count recovery (CRi). Complete remission (CR): Bone marrow blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) > 1000/μL; platelet count > 100,000/μL; independence of red cell transfusions. CR with incomplete recovery (CRi): All CR criteria except for ANC < 1000/μL or platelet count < 100,000/μL. Partial remission (PR): All hematologic criteria of CR; except decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%.
Time Frame	up to 1 year

Outcome Measure Data

Analysis Population Description

Only participants that started midostaurin therapy are included in the response assessment.

Arm/Group Title	Decitabine, Then Midostaurin
Arm/Group Description	INDUCTION THERAPY Subjects receive decitabine intravenously (IV) over 1 hour on days 1 to 10 and midostaurin orally (PO) twice daily (BID) on days 11 to 28. Treatment repeats every 28 days until documented bone marrow response is achieved or for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving documented bone marrow response by course 6 continue treatment with induction therapy; patients achieving response after course 6 proceed to post-remission therapy. POST-REMISSION THERAPY Subjects receive decitabine IV over 1 hour on days 1 to 5 and midostaurin PO BID on days 6 to 28. Treatment repeats every 28 days for up to 12 courses (including induction therapy) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for up to 1 year. Decitabine: Given IV Midostaurin: Given PO
Measure Participants	12
Count of Participants [Participants]	10 76.9%

3. Secondary Outcome

Title	Median Duration of Response (DoR)
Description	Response was assessed by evaluations conducted every 3 cycles (12 weeks). Once documented as partial response (PR), complete response (CR), or complete response with incomplete blood count recover (CRi), response status was confirmed every 12 weeks. In responding participants, duration of response was assessed from the start of treatment through the last documented response before documented progressive disease or death. The outcome is reported as the median value for duration of response, with full range. CR: Bone marrow blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; ANC > 1000/μL; platelet > 100,000/μL; independence of red cell transfusions. CRi: All CR criteria except ANC < 1000/μL or platelet count < 100,000/μL. PR: All hematologic criteria of CR; except decrease of bone marrow blast percentage to 5% to 25%; & decrease of pretreatment bone marrow blast percentage by at least 50%.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Does not include participants who did not achieve a documented clinical response. Participants who withdrew to receive hematopoietic cell transplant (HCT) are censored at the last assessment of response prior to HCT.

Arm/Group Title	Decitabine, Then Midostaurin
Arm/Group Description	INDUCTION THERAPY Subjects receive decitabine intravenously (IV) over 1 hour on days 1 to 10 and midostaurin orally (PO) twice daily (BID) on days 11 to 28. Treatment repeats every 28 days until documented bone marrow response is achieved or for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving documented bone marrow response by course 6 continue treatment with induction therapy; patients achieving response after course 6 proceed to post-remission therapy. POST-REMISSION THERAPY Subjects receive decitabine IV over 1 hour on days 1 to 5 and midostaurin PO BID on days 6 to 28. Treatment repeats every 28 days for up to 12 courses (including induction therapy) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for up to 1 year. Decitabine: Given IV Midostaurin: Given PO
Measure Participants	10
Median (Full Range) [weeks]	24

4. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	Progression-free survival (PFS) is reported as the number and proportion of participants who did not receive hematopoietic cell transplantation, and who did not experience disease progression or death for any reason within 2 years after starting midostaurin treatment. Progressive disease: Bone marrow blasts ≥ 5%; or reappearance of blasts in the blood; or development of extramedullary disease.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Only participants that started midostaurin therapy, and did not withdraw for hematopoietic cell transplantation, are included in the progression-free survival assessment.

Arm/Group Title	Decitabine, Then Midostaurin
Arm/Group Description	INDUCTION THERAPY Subjects receive decitabine intravenously (IV) over 1 hour on days 1 to 10 and midostaurin orally (PO) twice daily (BID) on days 11 to 28. Treatment repeats every 28 days until documented bone marrow response is achieved or for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving documented bone marrow response by course 6 continue treatment with induction therapy; patients achieving response after course 6 proceed to post-remission therapy. POST-REMISSION THERAPY Subjects receive decitabine IV over 1 hour on days 1 to 5 and midostaurin PO BID on days 6 to 28. Treatment repeats every 28 days for up to 12 courses (including induction therapy) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for up to 1 year. Decitabine: Given IV Midostaurin: Given PO
Measure Participants	9
Count of Participants [Participants]	0 0%

5. Secondary Outcome

Title	Overall Survival (OS)
Description	Survival is reported as the number and proportion of participants that received midostaurin who remained alive 2 years after starting midostaurin treatment.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Only participants that started midostaurin therapy are included in the overall survival assessment.

Arm/Group Title	Decitabine, Then Midostaurin
Arm/Group Description	INDUCTION THERAPY Subjects receive decitabine intravenously (IV) over 1 hour on days 1 to 10 and midostaurin orally (PO) twice daily (BID) on days 11 to 28. Treatment repeats every 28 days until documented bone marrow response is achieved or for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving documented bone marrow response by course 6 continue treatment with induction therapy; patients achieving response after course 6 proceed to post-remission therapy. POST-REMISSION THERAPY Subjects receive decitabine IV over 1 hour on days 1 to 5 and midostaurin PO BID on days 6 to 28. Treatment repeats every 28 days for up to 12 courses (including induction therapy) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for up to 1 year. Decitabine: Given IV Midostaurin: Given PO
Measure Participants	12
Count of Participants [Participants]	2 15.4%

Adverse Events

Arm/Group Title	Decitabine, Then Midostaurin
Arm/Group Description	INDUCTION THERAPY Subjects receive decitabine intravenously (IV) over 1 hour on days 1 to 10 and midostaurin orally (PO) twice daily (BID) on days 11 to 28. Treatment repeats every 28 days until documented bone marrow response is achieved or for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving documented bone marrow response by course 6 continue treatment with induction therapy; patients achieving response after course 6 proceed to post-remission therapy. POST-REMISSION THERAPY Subjects receive decitabine IV over 1 hour on days 1 to 5 and midostaurin PO BID on days 6 to 28. Treatment repeats every 28 days for up to 12 courses (including induction therapy) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for up to 1 year. Decitabine: Given IV Midostaurin: Given PO
All Cause Mortality
	Decitabine, Then Midostaurin
	Affected / at Risk (%)	# Events
Total	11/13 (84.6%)
Serious Adverse Events
	Decitabine, Then Midostaurin
	Affected / at Risk (%)	# Events
Total	13/13 (100%)
Blood and lymphatic system disorders
Renal failure	1/13 (7.7%)	1
Cardiac disorders
Atrial flutter	1/13 (7.7%)	1
Cardiac arrest	1/13 (7.7%)	1
Eye disorders
Vision blurred	1/13 (7.7%)	1
Pain, eye	1/13 (7.7%)	1
Gastrointestinal disorders
Bowel obstruction	1/13 (7.7%)	1
Bleeding (hemmorhage)	1/13 (7.7%)	1
General disorders
Kidney stones (nephrolithiasis)	1/13 (7.7%)	1
Swelling in arms and legs (peripheral edema)	1/13 (7.7%)	1
Immune system disorders
Neutropenic fever	13/13 (100%)	24
Infections and infestations
Herpetic stomatitis	1/13 (7.7%)	1
Sepsis	1/13 (7.7%)	1
Metabolism and nutrition disorders
Tumor lysis syndrome	1/13 (7.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor progression	7/13 (53.8%)	7
Nervous system disorders
Hematoma, subdural	1/13 (7.7%)	1
Unresponsive	1/13 (7.7%)	1
Respiratory, thoracic and mediastinal disorders
Anoxic brain injury	3/13 (23.1%)	3
Shortness of breath (dyspnea)	1/13 (7.7%)	1
Low oxygen in blood (hypoxemia)	1/13 (7.7%)	1
Low oxygen in tissues (hypoxia)	1/13 (7.7%)	1
Excess fluid around the lungs (pleural effusion)	1/13 (7.7%)	1
Lung infection (pneumonia)	5/13 (38.5%)	5
Respiratory distress	4/13 (30.8%)	4
Skin and subcutaneous tissue disorders
Rash	1/13 (7.7%)	1
Vascular disorders
Deep vein thrombosis	1/13 (7.7%)	1
Other (Not Including Serious) Adverse Events
	Decitabine, Then Midostaurin
	Affected / at Risk (%)	# Events
Total	13/13 (100%)
Blood and lymphatic system disorders
Neutropenic fever	4/13 (30.8%)	4
Hemoptysis	1/13 (7.7%)	1
Pancytopenia	5/13 (38.5%)	5
Chills	1/13 (7.7%)	1
Disease Progression	4/13 (30.8%)	4
Lymphocytopenia	1/13 (7.7%)	1
Increased transfusions	1/13 (7.7%)	1
Leukocytosis	1/13 (7.7%)	1
Macrocytosis	1/13 (7.7%)	1
Cytopenia	1/13 (7.7%)	1
Transfusion reaction to platelets	1/13 (7.7%)	1
Disseminated intravascular coagulation	1/13 (7.7%)	1
Cardiac disorders
Arrhythmia	5/13 (38.5%)	5
Hypertension	2/13 (15.4%)	2
Hypotension	1/13 (7.7%)	1
Eye disorders
Eye pain	1/13 (7.7%)	1
Gastrointestinal disorders
Nausea	3/13 (23.1%)	3
Taste alteration	1/13 (7.7%)	1
Diarrhea	3/13 (23.1%)	3
Constipation	5/13 (38.5%)	5
Abdominal / epigastric discomfort	1/13 (7.7%)	1
Hemorrhoids	1/13 (7.7%)	1
Gastroesophageal reflux disease	1/13 (7.7%)	1
Vomiting	2/13 (15.4%)	2
Cough	5/13 (38.5%)	5
Abdominal pain with bloating	2/13 (15.4%)	2
Poor appetite	2/13 (15.4%)	2
Metallic taste	1/13 (7.7%)	1
General disorders
Limb edema	5/13 (38.5%)	5
Weight loss	4/13 (30.8%)	4
Alopecia	3/13 (23.1%)	3
Dysgeusia	1/13 (7.7%)	1
Fatigue	7/13 (53.8%)	7
Mouth sores	2/13 (15.4%)	2
Fall	1/13 (7.7%)	1
Fracture	1/13 (7.7%)	1
Tingling and weakness	1/13 (7.7%)	1
Foot drop	1/13 (7.7%)	1
Blood-tinged sputum	1/13 (7.7%)	1
Pain on right thumb	1/13 (7.7%)	1
Shoulder pain	2/13 (15.4%)	2
Facial flushing	1/13 (7.7%)	1
Multi-organ dysfunction	1/13 (7.7%)	1
Leg pain	1/13 (7.7%)	1
Worsening of neuropathy	1/13 (7.7%)	1
Pain on left side of tongue	1/13 (7.7%)	1
Neck pain	1/13 (7.7%)	1
Infections and infestations
Stomatitis	4/13 (30.8%)	4
Cellulitis	3/13 (23.1%)	3
Sepsis	1/13 (7.7%)	1
Metabolism and nutrition disorders
Restless legs	1/13 (7.7%)	1
Acute renal failure	3/13 (23.1%)	3
Aspartate aminotransferase elevated	1/13 (7.7%)	1
Alanine aminotransferase elevated	1/13 (7.7%)	1
Nervous system disorders
Headache	1/13 (7.7%)	1
Hearing loss	1/13 (7.7%)	1
Altered mental status	2/13 (15.4%)	2
Confusion	1/13 (7.7%)	1
Agitation	1/13 (7.7%)	1
Delirium	1/13 (7.7%)	1
Lighted-headed	1/13 (7.7%)	1
Tinnitus	1/13 (7.7%)	1
Vertigo	1/13 (7.7%)	1
Sleep disorders	1/13 (7.7%)	1
Anxiety	1/13 (7.7%)	1
Distress	1/13 (7.7%)	1
Memory loss	1/13 (7.7%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	2/13 (15.4%)	2
Shortness of breath	4/13 (30.8%)	4
Hypoxia	1/13 (7.7%)	1
Viral illness	1/13 (7.7%)	1
Chest pain	1/13 (7.7%)	1
Decreased lung breathing sounds	1/13 (7.7%)	1
Invasive lung infection	1/13 (7.7%)	1
Wheezing	1/13 (7.7%)	1
Skin and subcutaneous tissue disorders
Rash	5/13 (38.5%)	5
Pruritus	1/13 (7.7%)	1
Subcutaneous nodule	3/13 (23.1%)	3
Desquamation on extremities	1/13 (7.7%)	1
Petechiae	1/13 (7.7%)	1
Lip lesions	2/13 (15.4%)	2
Lesion in buccal mucosa	3/13 (23.1%)	3
Diaphoretic	1/13 (7.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.