Nilotinib and Imatinib Mesylate After Donor Stem Cell Transplant in Treating Patients With ALL or CML

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00702403
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 40
• Locations: 5
• Arm: 1
• Actual Duration (Months): 63.6
• Patients Per Site: 8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase I/II trial is studying the side effects and best way to give nilotinib when given alone or sequentially after imatinib mesylate after donor stem cell transplant in treating patients with acute lymphoblastic leukemia or chronic myelogenous leukemia. Nilotinib and imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Condition or Disease	Intervention/Treatment	Phase
Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Philadelphia Positive Adult Acute Lymphoblastic Leukemia; Philadelphia Positive Childhood Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia	Drug: nilotinib; Drug: imatinib mesylate; Other: pharmacological study	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the safety of the administration of nilotinib between Day 81 and Day 365 after hematopoietic cell transplantation (HCT) in patients with Philadelphia chromosome positive (Ph+) leukemia.

SECONDARY OBJECTIVES:

1. To quantify the breakpoint cluster region (BCR)/Abelson murine leukemia (ABL) transcript load after HCT during tyrosine kinase inhibitor therapy in patients with Ph+ leukemia treated sequentially with imatinib (imatinib mesylate) and nilotinib from the time of engraftment.

2. To evaluate survival at 1 year in patients with Ph+ leukemia who received sequential imatinib and nilotinib from the time of engraftment.

3. To determine if imatinib can be co-administered with nilotinib for patients with rising levels of BCR/ABL on 2 consecutive occasions after HCT.

4. To confirm that imatinib can be delivered at an average daily dose of 400 mg at least 85% of the time in the majority of adults during the first 80 days after HCT.

5. To determine whether nilotinib can be administered safely at a daily dose of at least 300 mg (175 mg/m^2 in children < 17 years) at least 70% of the time to patients with imatinib resistant Ph+ leukemia during the first 80 days after HCT.

6. To determine treatment efficacy success at 1 year post-transplant as demonstrated by complete hematological remission, absence of Philadelphia chromosome, and not satisfying any of the criteria for treatment failure.

OUTLINE:

Beginning after engraftment and blood count recovery (21-28 days after allogeneic stem cell transplant), patients with imatinib-sensitive leukemia receive imatinib mesylate orally (PO) once daily (QD) until day 80 and then nilotinib PO twice daily (BID) on days 81-445. Patients with imatinib-resistant leukemia receive nilotinib PO BID beginning after engraftment and blood count recovery until day 445.

Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter Phase I/II Study of the Prophylactic Inhibition of BCR-ABL Tyrosine Kinase by Tasigna ® (Nilotinib) After Hematopoietic Cell Transplantation for Philadelphia Chromosome-Positive Leukemias.
• Actual Study Start Date: Aug 14, 2008
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (prophylactic inhibition of BCR-ABL tyrosine kinase) Beginning after engraftment and blood count recovery (21 to 28 days after allogeneic stem cell transplant), patients with imatinib-sensitive leukemia receive imatinib mesylate PO QD until day 80 and then nilotinib PO BID on days 81-445. Patients with imatinib-resistant leukemia receive nilotinib PO BID beginning after engraftment and blood count recovery until day 445. Treatment continues in the absence of disease progression or unacceptable toxicity.

Drug: nilotinib; Given PO; Other Names: AMN 107 Tasigna ; Drug: imatinib mesylate; Given PO; Other Names: CGP 57148 Gleevec Glivec ; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment Safety Failure [Up to 365 days post-transplant]

   Safety and tolerability of nilotinib therapy in patients with imatinib-sensitive leukemia graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0. Treatment safety failure is defined for a patient with imatinib sensitive Ph+ leukemia as the inability to be able to deliver at least 400 milligrams per day of nilotinib in adults, and 230 milligrams/m2 per day in children, for at least 85% of the time interval between 81 and 365 days after transplant. The overall study will be considered successful if nilotinib is deliverable to more than 75% of the study participants at this minimum specified dose intensity.

Secondary Outcome Measures

1. The Proportion of Patients at 1 Year With Treatment Efficacy Success [Up to 1 year]

   To be considered a treatment efficacy success at 1 year posttransplant, the patient's bone marrow must demonstrate complete hematological remission, absence of Philadelphia chromosomes, and not satisfy any of the criteria for treatment failure (>/= 1% aberrantly expressing marrow blasts by multiparameter flow cytometry, >5% BCR/ABL in marrow by fluorescent in situ hybridization, or >1 log rise in peripheral blood BCR/ABL by quantitative polymerase chain reaction (PCR) since day 80).

2. Survival [Up to 3 years]

   The proportion of study participants alive at 1, 2 and 3 years

3. Patients Alive With Out Relapse [Up to 1 year]

   The proportion of study participants alive and without hematologic, cytogenetic or molecular evidence of BCR/ABL-positive leukemia at 1 year

4. Relapse [1 and 3 years]

   The proportion of patients with hematologic, cytogenetic or molecular relapse of BCR/ABL-positive leukemia

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Body surface area >= 1 m^2

• Allogeneic HCT

• Acute lymphocytic leukemia (ALL) or chronic myelogenous leukemia (CML) characterized by the p190 and/or p210 BCR/ABL gene rearrangement

• CML in accelerated phase, blast crisis, or blast crisis remission as defined by World Health Organization (WHO) criteria

• CML in chronic phase if patient age =< 17 years or a patient of any age with CML in second chronic phase or beyond

• Patients with minimal residual disease (MRD) that is not declining in response to tyrosine kinase inhibitor therapy must be screened for the T315I and other mutations

• An appropriately matched related or unrelated donor

• Signed informed consent

• Patient must have a life expectancy of at least 2 months

• Stated willingness of the patient to comply with study procedures and reporting requirements

• Creatinine =< 2.0 x upper limit normal (ULN)

• Platelets > 20 x 10^9 /L

• Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN, conjugated bilirubin < 3 x ULN

• Serum potassium phosphorus, magnesium, and calcium >= lower limit normal (LLN) or correctable with supplements prior to first dose of study drug; calcium levels may be corrected for hypoalbuminemia

• Serum amylase and lipase < 1.5 x ULN

• Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing; postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential; male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug

• Careful rationalization with a view to discontinuing or considering alternatives to any concomitant medications that have potential to prolong the QT interval

Exclusion Criteria:

• Autologous transplant

• Non-myeloablative transplant

• Patient age > 17 years with CML in first chronic phase

• Aberrant antigen expression on marrow leukemic blasts >= 5% by multidimensional flow cytometric assay immediately before conditioning (CML patients in chronic phase exempt from flow cytometry screening)

• Ph+ ALL without complete cytogenetic remission immediately before conditioning

• Known T315I mutation

• Hypersensitivity to Gleevec or Tasigna

• Patients who are Tasigna-resistant or intolerant

• Central nervous system (CNS) involvement with leukemia at baseline (pre-imatinib therapy); CML chronic phase (CP), accelerated phase (AP) patients exempt from CNS involvement screening

• Female patients who are pregnant, breast-feeding, or of childbearing potential without a negative serum pregnancy test at screening; male or female patients of childbearing potential unwilling to use effective contraceptive precautions throughout the trial; post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential

• Life expectancy severely limited by diseases other than leukemia

• Myocardial infarction within one year prior to starting nilotinib

• Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, unstable angina)

• Absolute neutrophil count (ANC) less than 1500 per microliter at study entry despite the use of filgrastim (G-CSF)

• Impaired cardiac function, including any one of the following:

• Complete left bundle branch block or bifascicular block (right bundle branch block plus left anterior hemiblock) or use of ventricular-paced pacemaker

• Congenital long QT syndrome or a family history of long QT syndrome

• History of or presence of significant ventricular or atrial tachyarrhythmias

• Clinically significant resting bradycardia (< 50 beats per minute)

• Corrected QT interval (QTc) > 450 milliseconds on screening electrocardiogram (ECG); if QTc > 450 and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient rescreened for QTc

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University Hospitals and Clinics	Stanford	California	United States	94305
2	H Lee Moffitt Cancer Center and Research Institute Phase 2 Consortium	Tampa	Florida	United States	33612
3	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
4	Oregon Health and Science University	Portland	Oregon	United States	97239
5	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Paul Carpenter, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Paul Carpenter, Principal Investigator, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT00702403
• Other Study ID Numbers: 2223.00; NCI-2010-00402; P30CA015704; P01CA018029
• First Posted: Jun 20, 2008
• Last Update Posted: Aug 10, 2017
• Last Verified: Jul 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Blast Crisis; Leukemia, Myeloid, Accelerated Phase; Recurrence; Imatinib Mesylate

Study Results

Participant Flow

Arm/Group Title	Single Arm Nilotinib Relapse Prophylaxis
Arm/Group Description	Beginning after engraftment and blood count recovery (21 to 28 days after allogeneic stem cell transplant), patients with imatinib-sensitive leukemia receive imatinib mesylate PO QD until day 80 and then nilotinib PO BID on days 81-445. Patients with imatinib-resistant leukemia receive nilotinib PO BID beginning after engraftment and blood count recovery until day 445. Treatment continues in the absence of disease progression or unacceptable toxicity.
Period Title: From Consent to Engraftment
STARTED	57
Ineligible for Study Drug	17
COMPLETED	40
NOT COMPLETED	17
Period Title: From Consent to Engraftment
STARTED	40
Patient Drop-outs	27
COMPLETED	13
NOT COMPLETED	27

Baseline Characteristics

Arm/Group Title	Single Arm Nilotinib Relapse Prophylaxis
Arm/Group Description	Beginning after engraftment and blood count recovery (21 to 28 days after allogeneic stem cell transplant), patients with imatinib-sensitive leukemia receive imatinib mesylate PO QD until day 80 and then nilotinib PO BID on days 81-445. Patients with imatinib-resistant leukemia receive nilotinib PO BID beginning after engraftment and blood count recovery until day 445. Treatment continues in the absence of disease progression or unacceptable toxicity.
Overall Participants	40
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	42.5
Sex: Female, Male (Count of Participants)
Female	15 37.5%
Male	25 62.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 10%
Not Hispanic or Latino	36 90%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	3 7.5%
Asian	1 2.5%
Native Hawaiian or Other Pacific Islander	1 2.5%
Black or African American	0 0%
White	33 82.5%
More than one race	1 2.5%
Unknown or Not Reported	1 2.5%
Region of Enrollment (participants) [Number]
United States	40 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment Safety Failure
Description	Safety and tolerability of nilotinib therapy in patients with imatinib-sensitive leukemia graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0. Treatment safety failure is defined for a patient with imatinib sensitive Ph+ leukemia as the inability to be able to deliver at least 400 milligrams per day of nilotinib in adults, and 230 milligrams/m2 per day in children, for at least 85% of the time interval between 81 and 365 days after transplant. The overall study will be considered successful if nilotinib is deliverable to more than 75% of the study participants at this minimum specified dose intensity.
Time Frame	Up to 365 days post-transplant

Outcome Measure Data

Analysis Population Description

Critical to note are two "intention-to-treat" populations: the 1st (N=57) at time of consent, evolved into the second ITT population (N=40), because 17 subjects lost eligibility to begin relapse prophylaxis at engraftment. A 2nd wave of discontinuations occurred at or after Day 81 when all patients were to be switched from imatinib to nilotinib.

Arm/Group Title	Single Arm Nilotinib Relapse Prophylaxis
Arm/Group Description	Beginning after engraftment and blood count recovery (21 to 28 days after allogeneic stem cell transplant), patients with imatinib-sensitive leukemia receive imatinib mesylate PO QD until day 80 and then nilotinib PO BID on days 81-445. Patients with imatinib-resistant leukemia receive nilotinib PO BID beginning after engraftment and blood count recovery until day 445. Treatment continues in the absence of disease progression or unacceptable toxicity.
Measure Participants	40
Count of Participants [Participants]	13 32.5%

2. Secondary Outcome

Title	The Proportion of Patients at 1 Year With Treatment Efficacy Success
Description	To be considered a treatment efficacy success at 1 year posttransplant, the patient's bone marrow must demonstrate complete hematological remission, absence of Philadelphia chromosomes, and not satisfy any of the criteria for treatment failure (>/= 1% aberrantly expressing marrow blasts by multiparameter flow cytometry, >5% BCR/ABL in marrow by fluorescent in situ hybridization, or >1 log rise in peripheral blood BCR/ABL by quantitative polymerase chain reaction (PCR) since day 80).
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

The analysis population was considered in two ways: first the number of treatment success in the entire cohort (by "intention to treat"), and second the number of treatment successes among only those patients who did not die before 1 year from non-relapse mortality.

Arm/Group Title	Treatment (Prophylactic Inhibition of BCR-ABL Tyrosine Kinase)
Arm/Group Description	Beginning after engraftment and blood count recovery (21 to 28 days after allogeneic stem cell transplant), patients with imatinib-sensitive leukemia receive imatinib mesylate PO once daily until day 80 and then nilotinib PO twice daily on days 81-445. Patients with imatinib-resistant leukemia receive nilotinib PO twice daily beginning after engraftment and blood count recovery until day 445. Treatment continues in the absence of disease progression or unacceptable toxicity.
Measure Participants	40
By intention to treat	29 72.5%
Excluding early non-relapse deaths	29 72.5%

3. Secondary Outcome

Title	Survival
Description	The proportion of study participants alive at 1, 2 and 3 years
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Overall Survival (complete follow-up is available out to three years for all patients)

Arm/Group Title	Treatment (Prophylactic Inhibition of BCR-ABL Tyrosine Kinase)
Arm/Group Description	Beginning after engraftment and blood count recovery (21 to 28 days after allogeneic stem cell transplant), patients with imatinib-sensitive leukemia receive imatinib mesylate PO once daily until day 80 and then nilotinib PO twice daily on days 81-445. Patients with imatinib-resistant leukemia receive nilotinib PO twice daily beginning after engraftment and blood count recovery until day 445. Treatment continues in the absence of disease progression or unacceptable toxicity. nilotinib: Given PO imatinib mesylate: Given PO pharmacological study: Correlative studies
Measure Participants	40
Overall Survival at 1 year	31 77.5%
Overal Survival at 2 years	28 70%
Overall Survival at 3 years	28 70%

4. Secondary Outcome

Title	Patients Alive With Out Relapse
Description	The proportion of study participants alive and without hematologic, cytogenetic or molecular evidence of BCR/ABL-positive leukemia at 1 year
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

Proportion alive without relapse among the total number of patients with minimal residual disease follow-up data

Arm/Group Title	Single Arm Nilotinib Relapse Prophylaxis
Arm/Group Description	Beginning after engraftment and blood counts recover (21 to 28 days after allogeneic stem cell transplant), patients with imatinib-sensitive leukemia receive imatinib mesylate PO once daily until day 80 and then nilotinib PO twice daily on days 81-445. Patients with imatinib-resistant leukemia receive nilotinib PO twice daily beginning after engraftment and blood counts recover until day 445. Treatment continues in the absence of disease progression or unacceptable toxicity.
Measure Participants	40
Count of Participants [Participants]	29 72.5%

5. Secondary Outcome

Title	Relapse
Description	The proportion of patients with hematologic, cytogenetic or molecular relapse of BCR/ABL-positive leukemia
Time Frame	1 and 3 years

Outcome Measure Data

Analysis Population Description

Proportion of patients with hematologic, cytogenetic or molecular relapse of BCR/ABL-positive leukemia among those who did not die from non-relapse causes during the first year, and first 3-years after transplant.

Arm/Group Title	Treatment (Prophylactic Inhibition of BCR-ABL Tyrosine Kinase)
Arm/Group Description	Beginning after engraftment and blood count recovery (21 to 28 days after allogeneic stem cell transplant), patients with imatinib-sensitive leukemia receive imatinib mesylate PO once daily until day 80 and then nilotinib PO twice daily on days 81-445. Patients with imatinib-resistant leukemia receive nilotinib PO twice daily beginning after engraftment and blood count recovery until day 445. Treatment continues in the absence of disease progression or unacceptable toxicity.
Measure Participants	40
Proportion with relapse at 1 year	5 12.5%
Proportion with relapse at 3 years	6 15%

Adverse Events

Time Frame	Adverse Events: Conditioning through Day 100; Severe Adverse Events Conditioning >Day 100
Arm/Group Title	Single Arm Nilotinib Relapse Prophylaxis
Arm/Group Description	Beginning after engraftment and blood count recovery (21 to 28 days after allogeneic stem cell transplant), patients with imatinib-sensitive leukemia receive imatinib mesylate PO QD until day 80 and then nilotinib PO BID on days 81-445. Patients with imatinib-resistant leukemia receive nilotinib PO BID beginning after engraftment and blood count recovery until day 445. Treatment continues in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Single Arm Nilotinib Relapse Prophylaxis
	Affected / at Risk (%)	# Events
Total	9/40 (22.5%)
Serious Adverse Events
	Single Arm Nilotinib Relapse Prophylaxis
	Affected / at Risk (%)	# Events
Total	20/40 (50%)
Blood and lymphatic system disorders
Anemia	1/40 (2.5%)
Cardiac disorders
Pericardial effusion	1/40 (2.5%)
Myocardial Infarction	1/40 (2.5%)
Malignant hypertension	1/40 (2.5%)
Gastrointestinal disorders
Diarrhea	2/40 (5%)
Nausea	3/40 (7.5%)
Ascites	1/40 (2.5%)
Yeast esophagitis-Odynophagia	1/40 (2.5%)
Vomiting	2/40 (5%)
Anorexia	1/40 (2.5%)
Abdominal Cramping	1/40 (2.5%)
Headache	1/40 (2.5%)
Dehydration	1/40 (2.5%)
Transaminitis	1/40 (2.5%)
General disorders
Death, NOS	1/40 (2.5%)
Generalized weakness/fatiuge	1/40 (2.5%)
Multiorgan failure	1/40 (2.5%)
Hepatobiliary disorders
Acute acalculous cholecystitis	1/40 (2.5%)
Hepatic Failure	1/40 (2.5%)
Transaminitis	1/40 (2.5%)
Infections and infestations
Pseudomonas bacteremia	1/40 (2.5%)
Gram negative rod bacteremia with possible urosepsis	1/40 (2.5%)
Cytomegalovirus reactivation	1/40 (2.5%)
Fever/URI	2/40 (5%)
Staph Aureus Bacteremia	1/40 (2.5%)
Alpha-hemolytic Streptococcus	1/40 (2.5%)
Staph haemolyticus	1/40 (2.5%)
Gram-negative Bacteremia and Septic emboli	1/40 (2.5%)
Nodular pneumonia	1/40 (2.5%)
Bacterial pneumonia	1/40 (2.5%)
Acute lobular pneumonia with sepsis	1/40 (2.5%)
Haemophilus Influenza-Rhinovirus	1/40 (2.5%)
Pharyngitis	1/40 (2.5%)
Nervous system disorders
Depressed level of consciousness	1/40 (2.5%)
Seizure	1/40 (2.5%)
Psychiatric disorders
Confusion	1/40 (2.5%)
Altered mental status	1/40 (2.5%)
Acute encephalopathy	1/40 (2.5%)
Renal and urinary disorders
Hemorrhagic cystitis	1/40 (2.5%)
Renal colic	1/40 (2.5%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis	1/40 (2.5%)
Apnea	1/40 (2.5%)
Respiratory Failure	2/40 (5%)
Non-specific interstitial pneumonia	1/40 (2.5%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome	1/40 (2.5%)
Vascular disorders
Hypotension	1/40 (2.5%)
Other (Not Including Serious) Adverse Events
	Single Arm Nilotinib Relapse Prophylaxis
	Affected / at Risk (%)	# Events
Total	31/40 (77.5%)
Blood and lymphatic system disorders
Thrombocytopenia	19/40 (47.5%)
Anemia	7/40 (17.5%)
Neutropenia	7/40 (17.5%)
Lymphocytopenia	11/40 (27.5%)
Leukopenia	6/40 (15%)
INR Increased	1/40 (2.5%)
Cytopenia	2/40 (5%)
Gastrointestinal disorders
Diarrhea	2/40 (5%)
Mucositis	1/40 (2.5%)
Nausea	1/40 (2.5%)
Anorexia	1/40 (2.5%)
General disorders
Pain	1/40 (2.5%)
Localized Edema	1/40 (2.5%)
Infections and infestations
Klebsiella pneumonia pyelonephritis and positive urine culture	1/40 (2.5%)
Vancomycin resistant enterococcus and positive urine culture	1/40 (2.5%)
Bacteremia enterococcus faecalis	1/40 (2.5%)
Oral candidiasis	1/40 (2.5%)
CMV Reactivation	7/40 (17.5%)
Coagulase-negative staph	3/40 (7.5%)
CMV Enteritis	1/40 (2.5%)
Candidal esophagitis	1/40 (2.5%)
BK Virus	2/40 (5%)
Klebsiella and E.Coli and Positive Urine Culture	1/40 (2.5%)
S. epidermidis bacteremia	1/40 (2.5%)
Pseudomonas maltophilia Bacteremia	1/40 (2.5%)
GPC Bacteremia	1/40 (2.5%)
Multiorganism sepsis	1/40 (2.5%)
Metabolism and nutrition disorders
Elevated Serum AST/ALT	10/40 (25%)
Dehydration	1/40 (2.5%)
Hypoalbuminemia	2/40 (5%)
Anorexia/Nausea	1/40 (2.5%)
Increased Bilirubin	1/40 (2.5%)
Increased Alkaline Phosphate	2/40 (5%)
Hyponatremia	1/40 (2.5%)
Hyperkalemia	1/40 (2.5%)
Hypermagnesemia	1/40 (2.5%)
Hyperglycemia	1/40 (2.5%)
Increased creatinine-renal insufficiency	1/40 (2.5%)
Increased Lipase	1/40 (2.5%)
Musculoskeletal and connective tissue disorders
Generalized Muscle Weakness	1/40 (2.5%)
Psychiatric disorders
Delerium	1/40 (2.5%)
Depression	1/40 (2.5%)
Renal and urinary disorders
Renal Disease	1/40 (2.5%)
Hematuria	1/40 (2.5%)
Skin and subcutaneous tissue disorders
Skin Ulcer	1/40 (2.5%)

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.