Decitabine Followed by Mitoxantrone Hydrochloride, Etoposide, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01729845
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 52
• Locations: 3
• Arm: 1
• Actual Duration (Months): 51.4
• Patients Per Site: 17.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This phase I/II trial studies the side effects and best dose of decitabine followed by mitoxantrone hydrochloride, etoposide, and cytarabine and to see how well they work in treating patients with acute myeloid leukemia or high-risk myelodysplastic syndrome that has returned after a period of improvement or does not respond to treatment. Drugs used in chemotherapy, such as mitoxantrone hydrochloride, etoposide, cytarabine, and decitabine, 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 more than one drug (combination chemotherapy) may kill more cancer cells.

Condition or Disease	Intervention/Treatment	Phase
Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia	Drug: Cytarabine; Drug: Decitabine; Drug: Etoposide; Other: Laboratory Biomarker Analysis; Drug: Mitoxantrone Hydrochloride	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Estimate the maximum tolerated dose (MTD) of decitabine priming followed by sequential mitoxantrone hydrochloride/etoposide/cytarabine (MEC) chemotherapy in adults with relapsed/refractory acute myeloid leukemia (AML).

SECONDARY OBJECTIVES:

1. Determine, within the limits of a Phase 1/2 study, disease response and duration of remission.

2. Identify biomarkers (e.g., deoxyribonucleic acid [DNA] methylation and/or gene expression changes) associated with treatment responses.

OUTLINE: This is a phase I, dose-escalation study of decitabine followed by a phase II study.

Patients receive decitabine intravenously (IV) on days -9 to -5 (dose level 1), days -11 to -5 (dose level 2), or days -14 to -5 (dose level 3).

INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving complete response (CR) or CR with incomplete platelet count recovery (CRp) may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Mitoxantrone, Etoposide, and Cytarabine (MEC) Following Epigenetic Priming With Decitabine in Adults With Relapsed/Refractory Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndromes (MDS): A Phase 1/2 Study
• Actual Study Start Date: Dec 20, 2012
• Actual Primary Completion Date: Aug 25, 2016
• Actual Study Completion Date: Apr 3, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (decitabine, MEC) Patients receive decitabine IV on days -9 to -5 (dose level 1), days -11 to -5 (dose level 2), or days -14 to -5 (dose level 3). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy.

Drug: Cytarabine; Given IV; Other Names: .beta.-Cytosine arabinoside 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-.beta.-D-Arabinofuranosylcytosine 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-Beta-D-arabinofuranosylcytosine 1.beta.-D-Arabinofuranosylcytosine 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl- 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl- Alexan Ara-C ARA-cell Arabine Arabinofuranosylcytosine Arabinosylcytosine Aracytidine Aracytin Aracytine Beta-Cytosine Arabinoside CHX-3311 Cytarabinum Cytarbel Cytosar Cytosar-U Cytosine Arabinoside Cytosine-.beta.-arabinoside Cytosine-beta-arabinoside Erpalfa Starasid Tarabine PFS U 19920 U-19920 Udicil WR-28453 ; Drug: Decitabine; Given IV; Other Names: 5-Aza-2'-deoxycytidine Dacogen Decitabine for Injection Deoxyazacytidine Dezocitidine ; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16-213 VP-16 VP-16-213 ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Mitoxantrone Hydrochloride; Given IV; Other Names: CL 232315 DHAD DHAQ Dihydroxyanthracenedione Dihydrochloride Mitoxantrone Dihydrochloride Mitoxantroni Hydrochloridum Mitozantrone Hydrochloride Mitroxone Neotalem Novantrone Onkotrone Pralifan

Outcome Measures

Primary Outcome Measures

1. Most Efficacious and Tolerated Dosage of Decitabine (Period 1) [through day 45]

   MTD (most tolerated dose) of decitabine, measured in number of dose limiting toxicities. MTD defined as the highest dose in which the incidence of dose limiting toxicity is < 33%, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I)

Secondary Outcome Measures

1. Remission Rate Including CR and CRp [Up to 5 years]

   Complete remission (CR) and Complete remission with incomplete platelet recovery (CRp) categorized according to criteria recommended by International Working Groups: Complete resolution of disease-related symptoms and signs including palpable hepatosplenomegaly; hemoglobin level at least 110 g/L, platelet count at least 100x10^9/L, and absolute neutrophil count at least 1.0 x10^9/L. In addition, all 3 blood counts should be no higher than the upper normal limit; Normal leukocyte differential; Bone marrow histologic remission defined as the presence of age-adjusted normocellularity, no more than 5% myeloblasts, and an osteomyelofibrosis grade no higher than 1.

2. Duration of Relapse-free Survival (for Patients Achieving CR or CRp) [Up to 5 years]

   Categorized according to criteria recommended by International Working Groups.

3. Overall Survival [Up to 5 years]

   Survival measured as of day of last contact. Categorized according to criteria recommended by International Working Groups.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Prior diagnosis of "high-risk" myelodysplastic syndrome (MDS) (>= 10% blasts) or AML other than acute promyelocytic leukemia (APL) with t(15;17) (q22;q12) or variants according to the 2008 World Health Organization (WHO) classification; patients with biphenotypic AML are eligible

• Relapsed/persistent disease according to standard criteria requiring salvage therapy; outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution; flow cytometric analysis of peripheral blood and/or bone marrow should be performed according to institutional practice guidelines

• Patients with prior autologous or allogeneic hematopoietic cell transplantation (HCT) are eligible if relapse occurs provided symptoms of graft-versus host disease are well controlled with stable use of immunosuppressive agents

• Treatment-related mortality (TRM) score =< 9.2 as calculated with simplified model

• Should be off any active therapy for AML with the exception of hydroxyurea for at least 14 days prior to study registration unless patient has rapidly progressive disease, and all grade 2-4 non-hematologic toxicities should have resolved

• May have previously received monotherapy with demethylating agents for MDS or AML

• May have previously received chemotherapy with MEC for MDS or AML

• Patients with symptoms/signs of hyperleukocytosis or white blood cells (WBC) > 100,000/uL can be treated with leukapheresis or may receive up to 2 doses of cytarabine (up to 500 mg/m^2/dose) prior to enrollment

• Bilirubin =< 2 x institutional upper limit of normal (IULN) unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis (assessed within 7 days prior to study day 1)

• Serum creatinine =< 1.5 x IULN (assessed within 7 days prior to study day 1)

• Left ventricular ejection fraction >= 40%, assessed within 3 months prior to study day 1, e.g. by multi gated acquisition (MUGA) scan or echocardiography, or other appropriate diagnostic modality and no clinical evidence of congestive heart failure; if the patient had anthracycline-based therapy since the most recent cardiac assessment, cardiac evaluation should be repeated if there is clinical or radiographical suspicion of cardiac dysfunction, or if the previous cardiac assessment was abnormal

• Women of childbearing potential and men must agree to use adequate contraception

• Provide written informed consent

Exclusion Criteria:

• Refractory/relapsing myeloid blast crisis of chronic myeloid leukemia (CML), unless patient is not considered candidate for tyrosine kinase inhibitor treatment

• Concomitant illness associated with a likely survival of < 1 year

• Active systemic fungal, bacterial, viral, or other infection, unless disease is under treatment with anti-microbials and/or controlled or stable (e.g. if specific, effective therapy is not available/feasible or desired [e.g. chronic viral hepatitis, human immunodeficiency virus (HIV)]); patient needs to be clinically stable as defined as being afebrile and hemodynamically stable for 24 hours; patients with fever thought to be likely secondary to leukemia are eligible

• Known hypersensitivity to any study drug

• Pregnancy or lactation

• Patients may not be receiving any other investigational agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kadlec Clinic Hematology and Oncology	Kennewick	Washington	United States	99336
2	EvergreenHealth Medical Center	Kirkland	Washington	United States	98033
3	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Anna Halpern, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Anna Halpern, Principal Investigator, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT01729845
• Other Study ID Numbers: 2652.00; NCI-2012-02224; 2652; FH#2652; 2652.00; P30CA015704
• First Posted: Nov 20, 2012
• Last Update Posted: Feb 7, 2019
• Last Verified: Feb 1, 2019

• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes; Syndrome; Cytarabine; Etoposide; Podophyllotoxin; Mitoxantrone; Etoposide phosphate; Decitabine

Study Results

Participant Flow

Arm/Group Title	Dose Level 1: 5-Days of Decitabine-MEC	Dose Level 2: 7-Days of Decitabine-MEC	Dose Level 3: 10-days of Decitabine-MEC
Arm/Group Description	Patients receive decitabine IV days -9 to -5 (dose level 1). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy. Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Mitoxantrone Hydrochloride: Given IV	Patients receive decitabine IV days -11 to -5 (dose level 2). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy. Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Mitoxantrone Hydrochloride: Given IV	Patients receive decitabine IV days -14 to -5 (dose level 3). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy. Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Mitoxantrone Hydrochloride: Given IV
Period Title: Safety/Tolerability of Dec/MEC
STARTED	6	34	12
COMPLETED	6	34	12
NOT COMPLETED	0	0	0
Period Title: Safety/Tolerability of Dec/MEC
STARTED	0	22	0
COMPLETED	0	22	0
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Dose Level 1: 5-Days of Decitabine-MEC	Dose Level 2: 7-Days of Decitabine-MEC	Dose Level 3: 10-Days of Decitabine-MEC	Total
Arm/Group Description	Patients receive decitabine IV days -9 to -5 (dose level 1). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy. Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV	Patients receive decitabine IV days -11 to -5 (dose level 2). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy. Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV	Patients receive decitabine IV days -14 to -5 (dose level 3). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy. Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV	Total of all reporting groups
Overall Participants	6	34	12	52
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	54	55	57	55
Sex: Female, Male (Count of Participants)
Female	1 16.7%	16 47.1%	6 50%	23 44.2%
Male	5 83.3%	18 52.9%	6 50%	29 55.8%

Outcome Measures

1. Primary Outcome

Title	Most Efficacious and Tolerated Dosage of Decitabine (Period 1)
Description	MTD (most tolerated dose) of decitabine, measured in number of dose limiting toxicities. MTD defined as the highest dose in which the incidence of dose limiting toxicity is < 33%, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I)
Time Frame	through day 45

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Level 1: 5-Days of Decitabine-MEC	Dose Level 2: 7-Days of Decitabine-MEC	Dose Level 3: 10-Days of Decitabine-MEC
Arm/Group Description	Patients receive decitabine IV days -9 to -5 (dose level 1). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy. Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV Decitabine: Given IV Etoposide: Given IV Mitoxantrone Hydrochloride: Given IV	Patients receive decitabine IV days -11 to -5 (dose level 2). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy. Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV	Patients receive decitabine IV days -14 to -5 (dose level 1). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy. Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV
Measure Participants	6	12	12
Dose-limiting toxiticies	0	0	0
Complete Remission	1	5	3
Complete Remission, incomplete PLT recovery	2	1	2
Complete Remission, incomplete blood count recover	0	1	0
Morphologic leukemia-free state	0	0	3
Resistant Disease	1	3	4
Death (among those who received MEC)	2	1	0

2. Secondary Outcome

Title	Remission Rate Including CR and CRp
Description	Complete remission (CR) and Complete remission with incomplete platelet recovery (CRp) categorized according to criteria recommended by International Working Groups: Complete resolution of disease-related symptoms and signs including palpable hepatosplenomegaly; hemoglobin level at least 110 g/L, platelet count at least 100x10^9/L, and absolute neutrophil count at least 1.0 x10^9/L. In addition, all 3 blood counts should be no higher than the upper normal limit; Normal leukocyte differential; Bone marrow histologic remission defined as the presence of age-adjusted normocellularity, no more than 5% myeloblasts, and an osteomyelofibrosis grade no higher than 1.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Population includes all Dose Level 2 participants from both periods 1 and 2.

Arm/Group Title	Dose Level 2: 7-Days of Decitabine-MEC
Arm/Group Description	Patients receive decitabine IV days -11 to -5 (dose level 2). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy. Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV
Measure Participants	34
Count of Participants [Participants]	11 183.3%

3. Secondary Outcome

Title	Duration of Relapse-free Survival (for Patients Achieving CR or CRp)
Description	Categorized according to criteria recommended by International Working Groups.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Population includes all Dose Level 2 participants, from both periods 1 and 2, who achieved CR or CRp

Arm/Group Title	Dose Level 2: 7-Days of Decitabine-MEC
Arm/Group Description	Patients receive decitabine IV on days -11 to -5 (dose level 2) INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy. Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Mitoxantrone Hydrochloride: Given IV
Measure Participants	11
Median (Full Range) [Days]	150

4. Secondary Outcome

Title	Overall Survival
Description	Survival measured as of day of last contact. Categorized according to criteria recommended by International Working Groups.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Population includes all Dose Level 2 participants, from both periods 1 and 2.

Arm/Group Title	Dose Level 2: 7-Days of Decitabine-MEC
Arm/Group Description	Patients receive decitabine IV days -11 to -5 (dose level 2). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy. Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Mitoxantrone Hydrochloride: Given IV
Measure Participants	34
Median (Full Range) [days]	564

Adverse Events

Adverse Event Reporting Description	Death's reported were not reportable Serous adverse events per protocol. They were expected, or not related to drug and/or described in the protocol and consent form.
Arm/Group Title	Dose Level 1: 5-Days of Decitabine-MEC		Dose Level 2: 7-Days of Decitabine-MEC		Dose Level 3: 10-days of Decitabine-MEC
Arm/Group Description	Patients receive decitabine IV days -9 to -5 (dose level 1). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy. Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Mitoxantrone Hydrochloride: Given IV		Patients receive decitabine IV days -11 to -5 (dose level 2). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy. Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Mitoxantrone Hydrochloride: Given IV		Patients receive decitabine IV days -14 to -5 (dose level 3). INDUCTION THERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-5, etoposide IV on days 1-5, and cytarabine IV on days 1-5. Patients achieving CR or CR with CRp may receive up to 2 courses of induction therapy and up to 2 courses of consolidation therapy. Cytarabine: Given IV Decitabine: Given IV Etoposide: Given IV Mitoxantrone Hydrochloride: Given IV
All Cause Mortality
	Dose Level 1: 5-Days of Decitabine-MEC		Dose Level 2: 7-Days of Decitabine-MEC		Dose Level 3: 10-days of Decitabine-MEC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/6 (33.3%)		1/34 (2.9%)		0/12 (0%)
Serious Adverse Events
	Dose Level 1: 5-Days of Decitabine-MEC		Dose Level 2: 7-Days of Decitabine-MEC		Dose Level 3: 10-days of Decitabine-MEC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/34 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Dose Level 1: 5-Days of Decitabine-MEC		Dose Level 2: 7-Days of Decitabine-MEC		Dose Level 3: 10-days of Decitabine-MEC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		33/34 (97.1%)		12/12 (100%)
Blood and lymphatic system disorders
Febrile Neutropenia	5/6 (83.3%)		27/34 (79.4%)		11/12 (91.7%)
Cardiac disorders
Atrial Tachycardia	1/6 (16.7%)		0/34 (0%)		0/12 (0%)
Tropinemia/NSTEMI	0/6 (0%)		2/34 (5.9%)		0/12 (0%)
Gastrointestinal disorders
Diarrhea	0/6 (0%)		2/34 (5.9%)		2/12 (16.7%)
C Diff	0/6 (0%)		2/34 (5.9%)		2/12 (16.7%)
Nausea	1/6 (16.7%)		3/34 (8.8%)		1/12 (8.3%)
Esophagitis	0/6 (0%)		4/34 (11.8%)		0/12 (0%)
Colitis	0/6 (0%)		0/34 (0%)		1/12 (8.3%)
Cholecystitis	0/6 (0%)		2/34 (5.9%)		0/12 (0%)
Enteritis	0/6 (0%)		0/34 (0%)		1/12 (8.3%)
Vomiting	0/6 (0%)		3/34 (8.8%)		1/12 (8.3%)
General disorders
Edema limbs	0/6 (0%)		0/34 (0%)		1/12 (8.3%)
Infections and infestations
Sepsis	1/6 (16.7%)		10/34 (29.4%)		5/12 (41.7%)
Bacteremia	1/6 (16.7%)		12/34 (35.3%)		5/12 (41.7%)
Pneumonia	1/6 (16.7%)		1/34 (2.9%)		1/12 (8.3%)
Fungal Pneumonia	1/6 (16.7%)		8/34 (23.5%)		4/12 (33.3%)
Respiratory Tract infection	2/6 (33.3%)		0/34 (0%)		1/12 (8.3%)
Soft Tissue Infection	0/6 (0%)		4/34 (11.8%)		0/12 (0%)
Sinusitis	0/6 (0%)		3/34 (8.8%)		0/12 (0%)
Catheter Infection	0/6 (0%)		2/34 (5.9%)		0/12 (0%)
Investigations
Elevated Liver Function Tests	0/6 (0%)		1/34 (2.9%)		2/12 (16.7%)
Metabolism and nutrition disorders
Anorexia	0/6 (0%)		2/34 (5.9%)		2/12 (16.7%)
Hypokalemia	0/6 (0%)		2/34 (5.9%)		2/12 (16.7%)
Hyponatremia	2/6 (33.3%)		1/34 (2.9%)		3/12 (25%)
Tumor Lysis	0/6 (0%)		1/34 (2.9%)		1/12 (8.3%)
Hypophosphatemia	0/6 (0%)		2/34 (5.9%)		1/12 (8.3%)
Hypocalcemia	0/6 (0%)		0/34 (0%)		1/12 (8.3%)
Nervous system disorders
Syncope	0/6 (0%)		2/34 (5.9%)		0/12 (0%)
Psychiatric disorders
Anxiety	0/6 (0%)		1/34 (2.9%)		1/12 (8.3%)
Renal and urinary disorders
Acute Kidney Injury	0/6 (0%)		2/34 (5.9%)		1/12 (8.3%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/6 (16.7%)		5/34 (14.7%)		4/12 (33.3%)
Respitatory Failure	1/6 (16.7%)		5/34 (14.7%)		3/12 (25%)
Mucositis	1/6 (16.7%)		12/34 (35.3%)		0/12 (0%)
Elevated BR	0/6 (0%)		2/34 (5.9%)		0/12 (0%)
Skin and subcutaneous tissue disorders
Maculopapular Rash	1/6 (16.7%)		1/34 (2.9%)		1/12 (8.3%)
Vascular disorders
Hypotension	0/6 (0%)		2/34 (5.9%)		0/12 (0%)
Pulmonary Embolism	0/6 (0%)		2/34 (5.9%)		1/12 (8.3%)

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.