Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Chemotherapy Only Cytoreduction With Busulfan, Cyclophosphamide and Fludarabine

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00987480
• Collaborator: Boston Children's Hospital (Other), Children's Hospital Medical Center, Cincinnati (Other), Children's Hospital and Health System Foundation, Wisconsin (Other), Rockefeller University (Other), Fred Hutchinson Cancer Center (Other)
• Enrollment: 45
• Locations: 6
• Arm: 1
• Actual Duration (Months): 93.5
• Patients Per Site: 7.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a genetic disease (transmitted through the parents' genes) called Fanconi Anemia. Because of that genetic disease, the bone marrow has changed and now has failed, or has given rise to a preleukemia called myelodysplastic syndrome (MDS) or leukemia (acute myelogenous leukemia or AML).

Without treatment these complications of Fanconia anemia (FA) are fatal. The only treatment that can cure these complications is an allogeneic transplant of stem cells, meaning, giving the patient bone marrow cells from a healthy donor that can produce normal blood cells that will replace the bone marrow that is sick.

What has been given for the treatment of FA in the past is to use a combination of low doses of radiation to the whole body (total body irradiation) and low doses of the chemotherapy drugs (cyclophosphamide and fludarabine) before the transplant. However, the use of radiation can, later on, increase the chances of getting a second cancer of the skin, head or the neck. These chances of a second cancer are higher than normal in patients with FA.

The purpose of this study is to find out if the doctors can do the same thing with the same chemotherapy drugs used in the past. However physicians will use another chemotherapy drug called busulfan instead of the radiation. The goal of this study is to get rid of the short term and long term risks of the radiation. The first new part of this treatment will be to replace drugs for radiation with chemotherapy drugs.

Condition or Disease	Intervention/Treatment	Phase
Aplastic Anemia; Leukemia; Myelodysplastic Syndrome	Drug: Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.; Device: CliniMACS device	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter Phase II Trial of Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Chemotherapy Only Cytoreduction With Busulfan, Cyclophosphamide and Fludarabine
• Actual Study Start Date: Sep 25, 2009
• Actual Primary Completion Date: Jul 10, 2017
• Actual Study Completion Date: Jul 10, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: chemotherapy-based cytoreductive regimen plus a CD34+ selected This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease.

Drug: Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.; There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year.; Device: CliniMACS device; CD34+ T-cell depleted peripheral blood stem cell transplant

Outcome Measures

Primary Outcome Measures

1. Successful Neutrophil Engraftment [2 years]

2. The Incidence of Early Transplant Related Mortality [2 years]

3. The Incidence of Acute GvHD [100 days]

4. The Incidence of Chronic GvHD [2 years]

Secondary Outcome Measures

1. Overall Survival at 3 Years [3 years]

   Overall Survival is defined as time from date of transplant to event (death from any cause) or last follow-up.

2. Disease-free Survival at 3 Years [3 years]

   Defined as time from date of transplant to relapse, graft rejection or graft failure, or death. Primary non-engraftment is diagnosed when the participants fails to achieve an ANC >/= 500/ul at any time in the first 28 days post-transplant. For participants with MDS or AML, relapse will be analyzed as to type and genetic origin of the MDS/leukemic cells. These will be defined by an increasing number of blasts in the marrow over 5% by the presence of circulating peripheral blasts, or by the presence of blasts in any extramedullary site. Cytogenetic analysis of the marrow and/or peripheral blood will also be obtained for the diagnosis of relapse.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Patients must have a diagnosis of Fanconi anemia (confirmed by mitomycin C or diepoxybutane [DEB] chromosomal breakage testing at an approved laboratory).

• Hematologic Diagnosis and Status - Patients must have one of the following hematologic diagnoses:

• Severe Aplastic Anemia (SAA) with bone marrow cellularity of <25%, or Severe Isolated Single lineage Cytopenia

AND at least one of the following features:

• Platelet count <20 x 109/L or platelet transfusion dependence*

• ANC <1000 x 109/L

• Hgb <8 gm/dl or red cell transfusion dependence*

• Myelodysplastic Syndrome (MDS) (Appendix 1: MDS Classification) - MDS at any stage, based on either one of the following classifications:

• WHO Classification

• Refractory anemia and transfusion dependence*

• Any of other stages

• IPSS Classification

• Low risk (score 0) and transfusion dependence*

• Any other risk groups Score > or = to 0.5

• Acute Myelogenous Leukemia

• Patients with acute leukemia are included in this trial in remission, refractory or relapsed disease.

• Transfusion dependence will be defined as greater than ONE transfusion of platelets or red blood cells in the last year prior to evaluation on protocol.

• Donors:

• Donor choices will be determined by the investigators at each of the centers according to their own institutional criteria.

• All patients evaluated at trial sites and eligible for this trial by virtue of disease and lack of an HLA-genotypically matched related donor will be captured in the database of this trial. Patients who will be enrolled on this protocol must have one of the following donor choices:

• HLA-compatible Unrelated volunteer donors

• Patients who do not have a related HLA-matched donor but have an unrelated donor who is either matched at all A, B, C and DRB1 (8/8) loci or who is mismatched at 1/8 loci (A, B, C or DRB1) (7/8) as tested by DNA analysis (high resolution), will be eligible for entry on this protocol.

• HLA-mismatched Related donors

• Patients who do not have a related or unrelated HLA-compatible donor must have a healthy family member who is at least HLA-haplotype identical to the recipient. First degree related donors must have a normal DEB test.

• The donor must be healthy and willing and able to receive a 4-6 day course of G-CSF and undergo 1-3 daily leukaphereses.

• Related and Unrelated donors must be medically evaluated and fulfill the criteria for collection of PBSCs as per institutional guidelines.

• Patients:

• Patients and donors may be of either gender or any ethnic background.

• Patients must have a Karnofsky adult, or Lansky pediatric performance scale status > or = 70%.

• At the time of referral for transplantation, patients must have no co-existing medical problems that would significantly increase the risk of the transplant procedure.

• Patients must have adequate physical function measured by :

• Cardiac: asymptomatic or if symptomatic then 1) LVEF at rest must be > or = to 50% and must improve with exercise or 2) Shortening Fraction > or = to 29%

• Hepatic: < 5 x ULN SGOT and < 2.0 mg/dl total serum bilirubin.

• Renal: serum creatinine < or = to 1.5 mg/dl or if serum creatinine is outside the normal range, then CrCl > 60-ml/min/1.73 m2

• Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for hemoglobin)

• Each patient must be willing to participate as a research subject and must sign an informed consent form. Parent or legal guardians of patients who are minors will sign the informed consent form. Assents will be obtained as age appropriate.

• Female patients and donors must not be pregnant or breastfeeding at the time of signing consent. Women must be willing to undergo a pregnancy test prior to transplant and avoid becoming pregnant while on study.

Exclusion Criteria:

• Active CNS leukemic involvement

• Female patients who are pregnant (positive serum or urine HCG) or breast-feeding. Women of childbearing age must avoid becoming pregnant while on study.

• Active uncontrolled viral, bacterial or fungal infection

• Patient seropositive for HIV-I/II; HTLV -I/II

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Boston	Boston	Massachusetts	United States	02115
2	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
3	The Rockefeller University	New York	New York	United States	10065
4	Cincinnati Children's Hospital	Cincinnati	Ohio	United States	45229
5	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
6	Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• Boston Children's Hospital
• Children's Hospital Medical Center, Cincinnati
• Children's Hospital and Health System Foundation, Wisconsin
• Rockefeller University
• Fred Hutchinson Cancer Center

Investigators

• Principal Investigator: Faird Boulad, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 18, 2014

More Information

Additional Information:

• Memorial Sloan-Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00987480
• Other Study ID Numbers: 08-031; NCT00850317; NCT01082133
• First Posted: Oct 1, 2009
• Last Update Posted: Jul 10, 2018
• Last Verified: Jun 1, 2018

• Keywords provided by Memorial Sloan Kettering Cancer Center: Stem Cell Transplantation; Anemia; Busulfan; Cyclophosphamide; Fludarabine; 08-031
• Additional relevant MeSH terms: Anemia; Myelodysplastic Syndromes; Anemia, Aplastic; Fanconi Anemia; Cyclosporine; Cyclophosphamide; Busulfan; Fludarabine; Cyclosporins

Study Results

Participant Flow

Pre-assignment Detail	This is a multicenter site and MSK is the site responsible for data collection and analysis for all sites. 11 participants were enrolled at Memorial Sloan Kettering Cancer Center. The remaining 34 participants were enrolled at the participating institutions. This makes a total of 45 participants enrolled and treated on this study.

Arm/Group Title	Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Arm/Group Description	This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease. Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.: There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year.
Period Title: Overall Study
STARTED	45
COMPLETED	45
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Arm/Group Description	This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease. Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.: There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year.
Overall Participants	45
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	8.2
Sex: Female, Male (Count of Participants)
Female	25 55.6%
Male	20 44.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 11.1%
Not Hispanic or Latino	0 0%
Unknown or Not Reported	40 88.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 4.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 6.7%
White	36 80%
More than one race	0 0%
Unknown or Not Reported	4 8.9%
Region of Enrollment (Count of Participants)
United States	45 100%

Outcome Measures

1. Primary Outcome

Title	Successful Neutrophil Engraftment
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Arm/Group Description	This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease. Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.: There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year.
Measure Participants	45
Achieved neutrophil engraftment	44 97.8%
Did not achieve neutrophil engraftment	1 2.2%

2. Primary Outcome

Title	The Incidence of Early Transplant Related Mortality
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Arm/Group Description	This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease. Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.: There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year.
Measure Participants	45
Count of Participants [Participants]	0 0%

3. Primary Outcome

Title	The Incidence of Acute GvHD
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Arm/Group Description	This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease. Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.: There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year.
Measure Participants	45
Number [percentage of participants]	6.7 14.9%

4. Primary Outcome

Title	The Incidence of Chronic GvHD
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Arm/Group Description	This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease. Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.: There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year.
Measure Participants	45
Developed limited chronic GVHD	3 6.7%
Did not develop limited chronic GVHD	42 93.3%

5. Secondary Outcome

Title	Overall Survival at 3 Years
Description	Overall Survival is defined as time from date of transplant to event (death from any cause) or last follow-up.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Arm/Group Description	This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease. Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.: There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year.
Measure Participants	45
Number [percentage of participants]	80 177.8%

6. Secondary Outcome

Title	Disease-free Survival at 3 Years
Description	Defined as time from date of transplant to relapse, graft rejection or graft failure, or death. Primary non-engraftment is diagnosed when the participants fails to achieve an ANC >/= 500/ul at any time in the first 28 days post-transplant. For participants with MDS or AML, relapse will be analyzed as to type and genetic origin of the MDS/leukemic cells. These will be defined by an increasing number of blasts in the marrow over 5% by the presence of circulating peripheral blasts, or by the presence of blasts in any extramedullary site. Cytogenetic analysis of the marrow and/or peripheral blood will also be obtained for the diagnosis of relapse.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Arm/Group Description	This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease. Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.: There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year.
Measure Participants	45
Number [percentage of participants]	77.8 172.9%

Adverse Events

Time Frame	1 year
Arm/Group Title	Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Arm/Group Description	This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease
All Cause Mortality
	Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
	Affected / at Risk (%)	# Events
Total	9/45 (20%)
Serious Adverse Events
	Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
	Affected / at Risk (%)	# Events
Total	11/45 (24.4%)
Blood and lymphatic system disorders
Blood/Bone Marrow, Other	1/45 (2.2%)
Cardiac disorders
Cardiopulmonary arrest, cause unknkown	1/45 (2.2%)
Gastrointestinal disorders
Gastrointestinal, other	1/45 (2.2%)
Hemorrhage, Oral cavity	1/45 (2.2%)
Hemorrhage, Stoma (GI)	1/45 (2.2%)
Ileus, GI (func obstruction of bowel)	1/45 (2.2%)
Mucositis (Clin exam)- Oral cavity	1/45 (2.2%)
General disorders
Death NOS	3/45 (6.7%)
Infections and infestations
Inf norm ANC/gr1/2 neut-Blood	1/45 (2.2%)
Inf norm ANC/gr1/2 neut-Meningitis(meninges)	1/45 (2.2%)
Inf norm ANC/gr1/2 neut-Myositis infection(muscle)	1/45 (2.2%)
Infection w/ Gr 3/4 neut, Blood	1/45 (2.2%)
Infection, other	4/45 (8.9%)
Investigations
Bilirubin (hyperbilirubinemia)	1/45 (2.2%)
Nervous system disorders
Neurology - Other (specify)	1/45 (2.2%)
Neuropathy: motor	1/45 (2.2%)
Seizure	1/45 (2.2%)
Psychiatric disorders
Confusion	1/45 (2.2%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/45 (2.2%)
Hemorrhage, Respiratory tract NOS	1/45 (2.2%)
Hypoxia	7/45 (15.6%)
Pneumonitis/pulm infiltrates	2/45 (4.4%)
Pulm/upp respiratory - Other (spec)	1/45 (2.2%)
Pulmonary hypertension	1/45 (2.2%)
Other (Not Including Serious) Adverse Events
	Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
	Affected / at Risk (%)	# Events
Total	31/45 (68.9%)
Blood and lymphatic system disorders
Lymphopenia	8/45 (17.8%)
Gastrointestinal disorders
Mucositis (Clin exam)- Pharynx	4/45 (8.9%)
Mucositis (Clin exam)- Oral cavity	15/45 (33.3%)
Infections and infestations
Infection, other	5/45 (11.1%)
Investigations
Aspartate aminotransferase increased	3/45 (6.7%)
Bicarbonate, serum-low	3/45 (6.7%)
Blood bilirubin increased	3/45 (6.7%)
Alanine aminotransferase increased	5/45 (11.1%)
INR	6/45 (13.3%)
Alkaline phosphatase	7/45 (15.6%)
PTT	7/45 (15.6%)
Creatinine	8/45 (17.8%)
Hemoglobin	8/45 (17.8%)
Leukocytes (total WBC)	8/45 (17.8%)
Neutrophils/granulocytes (ANC/AGC)	8/45 (17.8%)
Platelets	8/45 (17.8%)
AST, SGOT	10/45 (22.2%)
ALT, SGPT	11/45 (24.4%)
Bilirubin (hyperbilirubinemia)	11/45 (24.4%)
Metabolism and nutrition disorders
Sodium, high (hypernatremia)	3/45 (6.7%)
Glucose, low (hypoglycemia)	4/45 (8.9%)
Hypermagnesemia	4/45 (8.9%)
Phosphate, low (hypophosphatemia)	4/45 (8.9%)
Hyperglycemia	6/45 (13.3%)
Magnesium, high (hypermagnesemia)	6/45 (13.3%)
Magnesium, low (hypomagnesemia)	6/45 (13.3%)
Trglycrde, high (hypertriglyceridemia)	6/45 (13.3%)
Potassium, high (hyperkalemia)	7/45 (15.6%)
Albumin, low (hypoalbuminemia)	8/45 (17.8%)
Sodium, low (hyponatremia)	9/45 (20%)
Potassium, low (hypokalemia)	10/45 (22.2%)
Glucose, high (hyperglycemia)	14/45 (31.1%)
Vascular disorders
Hypertension	8/45 (17.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.