HSCT for High Risk Inherited Inborn Errors

• Sponsor: Masonic Cancer Center, University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT00383448
• Collaborator: (none)
• Enrollment: 38
• Location: 1
• Arm: 1
• Duration (Months): 96
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Hematopoietic stem cell transplantation has proven effective therapy for individuals with adrenoleukodystrophy (ALD), metachromatic leukodystrophy (MLD) or globoid cell leukodystrophy (GLD, or Krabbe disease). This protocol also considers other inherited metabolic diseases such as, but not limited to, GM1 gangliosidosis, Tay Sachs disease, Sanfilippo syndrome or Sandhoff disease, I-cell disease (mucolipidosis II).

For patients with advanced or rapidly progressive disease, the morbidity and mortality with transplantation is unacceptably high. Unfortunately, there are no viable alternative therapeutic options for these patients; if transplantation is not performed the patients are sent home to die. Our group at Minnesota has developed a new protocol incorporating transplantation using a reduced intensity conditioning regimen designed to decrease toxicity associated with the transplant procedure. This regimen will make use of the drug clofarabine, which has lympholytic and immune suppressive properties without the neurologic toxicity observed in the related compound, fludarabine, commonly used for transplantation. In addition, several agents providing anti-oxidant and anti-inflammatory properties will be used to assist in the stabilization of the disease processes. This revised transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol, 2) the mortality associated with transplant by day 100, 3) patient outcomes, based on differential neurologic, neuropsychologic, imaging and biologic evaluations prior to transplantation and at designated points after transplantation (day 100, 6 months, 1, 2 and 5 years). Additional biologic studies will include pharmacokinetics of clofarabine and mycophenolate mofetil (MMF). In addition, for patients undergoing lumbar puncture studies, cerebrospinal fluid (CSF) will be requested for determinations of biologic parameters.

Condition or Disease	Intervention/Treatment	Phase
Adrenoleukodystrophy; Metachromatic Leukodystrophy; Globoid Cell Leukodystrophy; Tay Sachs Disease; Sandhoffs Disease; Wolman Disease; I-Cell Disease; Sanfilippo Syndrome; GM1 Gangliosidosis	Drug: Clofarabine; Procedure: Total body Irradiation; Drug: Melphalan; Biological: Hematopoietic Stem Cell Transplantation; Drug: Alemtuzumab; Drug: mycophenylate mofetil; Device: Cyclosporine A; Drug: Hydroxyurea	Phase 2

Detailed Description

Hematopoietic stem cell transplantation has proven effective therapy for individuals with adrenoleukodystrophy (ALD), metachromatic leukodystrophy (MLD) or globoid cell leukodystrophy (GLD, or Krabbe disease). However, for patients with advanced or rapidly progressive disease, the morbidity and mortality with transplantation is unacceptably high. Unfortunately, there are no viable alternative therapeutic options for these patients; if transplantation is not performed the patients are sent home to die. Our group at Minnesota has developed a new protocol incorporating transplantation using a reduced intensity conditioning regimen designed to decrease toxicity associated with the transplant procedure. This regimen will make use of the drug clofarabine, which has lympholytic and immune suppressive properties without the neurologic toxicity observed in the related compound, fludarabine, commonly used for transplantation. In addition, several agents providing anti-oxidant and anti-inflammatory properties will be used to assist in the stabilization of the disease processes. This revised transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol, 2) the mortality associated with transplant by day 100, 3) patient outcomes, based on differential neurologic, neuropsychologic, imaging and biologic evaluations prior to transplantation and at designated points after transplantation (day 100, 6 months, 1, 2 and 5 years). Additional biologic studies will include pharmacokinetics of clofarabine and mycophenolate mofetil (MMF), develop experience in kinetics of N-acetylcysteine, and evaluate biologic markers of oxidative status during transplantation. In addition, for patients undergoing lumbar puncture studies, cerebrospinal fluid (CSF) will be requested for determinations of biologic parameters.

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment of High Risk, Inherited Lysosomal And Peroxisomal Disorders by Reduced Intensity Hematopoietic Stem Cell Transplantation
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Sep 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treated Patients Patients receiving chemotherapy (Hydroxyurea, Alemtuzumab, Clofarabine, Melphalan), Hematopoietic Stem Cell Transplantation and radiation therapy (Total body Irradiation) mycophenylate mofetil and cyclosporine A.

Drug: Clofarabine; days -7 through -3: 40 mg/m^2 intravenously over 2 hours; Other Names: Clolar ; Procedure: Total body Irradiation; Administration of TBI: The dose of TBI will be 200 cGy given in a single fraction on day -1. The dose rate will be between 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus.; Other Names: TLI ; Drug: Melphalan; day -2: 140 mg/m^2 intravenously over 30 minutes; Other Names: Alkeran ; Biological: Hematopoietic Stem Cell Transplantation; receives infusion of stem cells on day 0; Drug: Alemtuzumab; 0.3 mg/kg intravenously (IV) days -12 through -8; Other Names: Campath 1-H ; Drug: mycophenylate mofetil; Day -3 through Day 30: 1 gram three times daily (total daily dose 3 grams/day) if the recipient is >50 kg, or 15 mg/kg three times daily if the recipient is ≤50 kg. The same dosage is used orally or intravenously. Consider dose modification if renal impairment (GFR<25 mL/minute corrected); Other Names: MMF ; Device: Cyclosporine A; Patients will receive CsA therapy beginning on day -3. Dosing of CsA will be 2.5 mg/kg/dose intravenously (IV); if the recipient body weight is <40 kg, dosing will be 3 times daily, and if > 40 kg twice daily. An attempt will be made to maintain a trough cyclosporine level of 250 mg/L to 350 mg/L. Once the patient can tolerate oral medications and has a normal gastrointestinal transit time, CsA will be converted to an oral form at a dose 2.5 x the current IV dose (maximum 12.5 mg/kg/day as initial oral dose). CsA taper begins at day +100.; Other Names: CsA ; Drug: Hydroxyurea; hydroxyurea (HU) beginning day -28 and continuing through alemtuzumab administration; Other Names: Hydria HU

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Donor Cell Engraftment [Day 100]

   Donor Cell Engraftment is defined as the process of transplanted stem cells reproducing new cells.

Secondary Outcome Measures

1. Number of Patients Whose Death Was Related to the Transplant [Day 100]

   In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.

2. Concentrations of Mycophenylate Mofetil (MMF) [Day 3]

   MMF levels are to be sent on day +3 to the main laboratory for determinations of MMF kinetics. Data was not collected on this outcome measure and is not available for reporting.

3. Number of Patients With Acute Graft Versus Host Disease (GVHD) [Day 100]

   Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host. Acute GVHD can occur once the donor's cells have engrafted in the transplant recipient. The symptoms typically appear within weeks after transplant.

4. Number of Patients With Chronic Graft Versus Host Disease (GVHD) [1 year]

   Graft-Versus-Host Disease is a severe complication created by infusion of donor cells into a foreign host. Chronic GVHD can appear at any time after allogeneic transplant or several years after transplant.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adrenoleukodystrophy: Patients from 0-55 years of age diagnosed with ALD as determined by very long chain fatty acid testing will be eligible for this protocol if they have evidence of cerebral or cerebellar disease based on MRI testing, AND they are determined high risk for any of the following reasons:

1. Age >18 years

2. MRI score >10

3. Evidence of aggressive disease that in the judgment of the Inherited Metabolic and Storage Disease group is sufficiently concerning to consider transplantation with a reduced intensity regimen instead of a standard full preparative regimen.

• Metachromatic Leukodystrophy: Patients from 0-55 years of age diagnosed with MLD as determined by determinations of arylsulfatase A testing will be eligible for this protocol IF they are determined high risk for any of the following reasons:

1. Age >18 years

2. Symptomatic disease, as based on neurologic examination, or evidence of deterioration based on subsequent neuropsychologic evaluations.

3. Evidence of aggressive disease such as rapidly changing MRI determinations that in the judgment of the Inherited Metabolic and Storage Disease group is sufficiently concerning to consider transplantation with a reduced intensity regimen instead of a standard full preparative regimen.

• Globoid Cell Leukodystrophy: Patients from 0-55 years of age diagnosed with GLD as determined by determinations of galactocerebrosidase testing will be eligible for this protocol IF they are determined high risk for any of the following reasons:

1. Age >18 years

2. Symptomatic disease, as based on neurologic examination, or evidence of deterioration based on subsequent neuropsychologic evaluations.

3. Evidence of aggressive disease such as rapidly changing MRI determinations that in the judgment of the Inherited Metabolic and Storage Disease group is sufficiently concerning to consider transplantation with a reduced intensity regimen instead of a standard full preparative regimen.

• Patients with GM1 gangliosidosis, Tay Sachs disease, Sanfilippo syndrome, Wolman disease or Sandhoff disease or other inherited metabolic diseases including but not limited to I-cell disease (mucolipidosis II) who are determined to be sufficiently advanced or high risk based on the following reasons:

1. Symptomatic disease, as based on neurologic examination, or evidence of deterioration based on subsequent neuropsychologic evaluations.

2. Evidence of an expected poor outcome based on genetic testing or a prior family history of aggressive disease.

3. Other metabolic disorders, including but not limited to I-cell disease, that are deemed to be high-risk for a poor outcome with a standard transplant regimen due to anticipated toxicity based on experience gained at the University of Minnesota or other centers.

Exclusion criteria:

• Major organ dysfunction.

• Advanced Disease Exclusion: Following evaluation, if a consensus of the members of the Inherited Metabolic and Storage Disease Program is that a patient is too advanced to benefit in a measurable and meaningful way from transplant, this will be communicated to the family, and transplant will not be offered. Measures to assist in those determinations may include: neurologic/neurocognitive functions such as activities of daily living, motor function, vision, hearing, interaction with environment, toileting, swallowing, or other standardized measures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

• Masonic Cancer Center, University of Minnesota

Investigators

• Principal Investigator: Paul Orchard, MD, Masonic Cancer Center, University of Minnesota

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT00383448
• Other Study ID Numbers: MT2006-14; 0606M87246
• First Posted: Oct 3, 2006
• Last Update Posted: Jul 11, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by Masonic Cancer Center, University of Minnesota: Stem cell transplantation; Inborn errors of metabolism; Adrenoleukodystrophy (ALD); Metachromatic leukodystrophy (MLD); Globoid cell leukodystrophy (GLD or Krabbe); Tay Sachs; Sandhoff; Sanfilippo syndrome; Mucopolysaccharidosis III (MPS-III); GM1 gangliosidosis; I-cell; mucolipidosis
• Additional relevant MeSH terms: Mucolipidoses; Adrenoleukodystrophy; Gangliosidoses; Leukodystrophy, Metachromatic; Tay-Sachs Disease; Gangliosidosis, GM1; Sandhoff Disease; Leukodystrophy, Globoid Cell; Mucopolysaccharidosis III; Wolman Disease; Cyclosporine; Melphalan; Alemtuzumab; Hydroxyurea; Clofarabine; Cyclosporins

Study Results

Participant Flow

Arm/Group Title	Treated Patients
Arm/Group Description	Patients receiving chemotherapy (Hydroxyurea, Alemtuzumab, Clofarabine, Melphalan), Hematopoietic Stem Cell Transplantation and radiation therapy (Total body Irradiation) mycophenylate mofetil and cyclosporine A. Clofarabine: days -7 through -3: 40 mg/m^2 intravenously over 2 hours Total body Irradiation: Administration of TBI: The dose of TBI will be 200 cGy given in a single fraction on day -1. The dose rate will be between 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus. Melphalan: day -2: 140 mg/m^2 intravenously over 30 minutes Hematopoietic Stem Cell Transplantation: receives infusion of stem cells on day 0 Alemtuzumab: 0.3 mg/kg intravenously (IV) days -12 through -8 mycophenylate mofetil: Day -3 through Day 30: 1 gram three times daily (total daily dose 3 grams/day) if the recipient is >50 kg, or 15 mg/kg three times daily if the recipient is ≤50 kg. The same dosage is used orally or intravenously.
Period Title: Overall Study
STARTED	38
COMPLETED	38
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treated Patients
Arm/Group Description	Patients receiving chemotherapy (Hydroxyurea, Alemtuzumab, Clofarabine, Melphalan), Hematopoietic Stem Cell Transplantation and radiation therapy (Total body Irradiation) mycophenylate mofetil and cyclosporine A. Clofarabine: days -7 through -3: 40 mg/m^2 intravenously over 2 hours Total body Irradiation: Administration of TBI: The dose of TBI will be 200 cGy given in a single fraction on day -1. The dose rate will be between 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus. Melphalan: day -2: 140 mg/m^2 intravenously over 30 minutes Hematopoietic Stem Cell Transplantation: receives infusion of stem cells on day 0 Alemtuzumab: 0.3 mg/kg intravenously (IV) days -12 through -8 mycophenylate mofetil: Day -3 through Day 30: 1 gram three times daily (total daily dose 3 grams/day) if the recipient is >50 kg, or 15 mg/kg three times daily if the recipient is ≤50 kg. The same dosage is used orally or intravenously.
Overall Participants	38
Age (Count of Participants)
<=18 years	32 84.2%
Between 18 and 65 years	6 15.8%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	8 21.1%
Male	30 78.9%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Donor Cell Engraftment
Description	Donor Cell Engraftment is defined as the process of transplanted stem cells reproducing new cells.
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

One patient was not evaluable due to an early death.

Arm/Group Title	Treated Patients
Arm/Group Description	Patients receiving chemotherapy (Hydroxyurea, Alemtuzumab, Clofarabine, Melphalan), Hematopoietic Stem Cell Transplantation and radiation therapy (Total body Irradiation) mycophenylate mofetil and cyclosporine A. Clofarabine: days -7 through -3: 40 mg/m^2 intravenously over 2 hours Total body Irradiation: Administration of TBI: The dose of TBI will be 200 cGy given in a single fraction on day -1. The dose rate will be between 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus. Melphalan: day -2: 140 mg/m^2 intravenously over 30 minutes Hematopoietic Stem Cell Transplantation: receives infusion of stem cells on day 0 Alemtuzumab: 0.3 mg/kg intravenously (IV) days -12 through -8 mycophenylate mofetil: Day -3 through Day 30: 1 gram three times daily (total daily dose 3 grams/day) if the recipient is >50 kg, or 15 mg/kg three times daily if the recipient is ≤50 kg. The same dosage is used orally or intravenously.
Measure Participants	37
Count of Participants [Participants]	26 68.4%

2. Secondary Outcome

Title	Number of Patients Whose Death Was Related to the Transplant
Description	In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treated Patients
Arm/Group Description	Patients receiving chemotherapy (Hydroxyurea, Alemtuzumab, Clofarabine, Melphalan), Hematopoietic Stem Cell Transplantation and radiation therapy (Total body Irradiation) mycophenylate mofetil and cyclosporine A. Clofarabine: days -7 through -3: 40 mg/m^2 intravenously over 2 hours Total body Irradiation: Administration of TBI: The dose of TBI will be 200 cGy given in a single fraction on day -1. The dose rate will be between 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus. Melphalan: day -2: 140 mg/m^2 intravenously over 30 minutes Hematopoietic Stem Cell Transplantation: receives infusion of stem cells on day 0 Alemtuzumab: 0.3 mg/kg intravenously (IV) days -12 through -8 mycophenylate mofetil: Day -3 through Day 30: 1 gram three times daily (total daily dose 3 grams/day) if the recipient is >50 kg, or 15 mg/kg three times daily if the recipient is ≤50 kg. The same dosage is used orally or intravenously.
Measure Participants	38
Count of Participants [Participants]	2 5.3%

3. Secondary Outcome

Title	Concentrations of Mycophenylate Mofetil (MMF)
Description	MMF levels are to be sent on day +3 to the main laboratory for determinations of MMF kinetics. Data was not collected on this outcome measure and is not available for reporting.
Time Frame	Day 3

Outcome Measure Data

Analysis Population Description

Data was not collected on this outcome measure and is not available for reporting.

Arm/Group Title	Treated Patients
Arm/Group Description	Patients receiving chemotherapy (Hydroxyurea, Alemtuzumab, Clofarabine, Melphalan), Hematopoietic Stem Cell Transplantation and radiation therapy (Total body Irradiation) mycophenylate mofetil and cyclosporine A.
Measure Participants	0

4. Secondary Outcome

Title	Number of Patients With Acute Graft Versus Host Disease (GVHD)
Description	Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host. Acute GVHD can occur once the donor's cells have engrafted in the transplant recipient. The symptoms typically appear within weeks after transplant.
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treated Patients
Arm/Group Description	Patients receiving chemotherapy (Hydroxyurea, Alemtuzumab, Clofarabine, Melphalan), Hematopoietic Stem Cell Transplantation and radiation therapy (Total body Irradiation) mycophenylate mofetil and cyclosporine A. Clofarabine: days -7 through -3: 40 mg/m^2 intravenously over 2 hours Total body Irradiation: Administration of TBI: The dose of TBI will be 200 cGy given in a single fraction on day -1. The dose rate will be between 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus. Melphalan: day -2: 140 mg/m^2 intravenously over 30 minutes Hematopoietic Stem Cell Transplantation: receives infusion of stem cells on day 0 Alemtuzumab: 0.3 mg/kg intravenously (IV) days -12 through -8 mycophenylate mofetil: Day -3 through Day 30: 1 gram three times daily (total daily dose 3 grams/day) if the recipient is >50 kg, or 15 mg/kg three times daily if the recipient is ≤50 kg. The same dosage is used orally or intravenously.
Measure Participants	38
Count of Participants [Participants]	3 7.9%

5. Secondary Outcome

Title	Number of Patients With Chronic Graft Versus Host Disease (GVHD)
Description	Graft-Versus-Host Disease is a severe complication created by infusion of donor cells into a foreign host. Chronic GVHD can appear at any time after allogeneic transplant or several years after transplant.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treated Patients
Arm/Group Description	Patients receiving chemotherapy (Hydroxyurea, Alemtuzumab, Clofarabine, Melphalan), Hematopoietic Stem Cell Transplantation and radiation therapy (Total body Irradiation) mycophenylate mofetil and cyclosporine A. Clofarabine: days -7 through -3: 40 mg/m^2 intravenously over 2 hours Total body Irradiation: Administration of TBI: The dose of TBI will be 200 cGy given in a single fraction on day -1. The dose rate will be between 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus. Melphalan: day -2: 140 mg/m^2 intravenously over 30 minutes Hematopoietic Stem Cell Transplantation: receives infusion of stem cells on day 0 Alemtuzumab: 0.3 mg/kg intravenously (IV) days -12 through -8 mycophenylate mofetil: Day -3 through Day 30: 1 gram three times daily (total daily dose 3 grams/day) if the recipient is >50 kg, or 15 mg/kg three times daily if the recipient is ≤50 kg. The same dosage is used orally or intravenously.
Measure Participants	38
Count of Participants [Participants]	2 5.3%

Adverse Events

Arm/Group Title	Treated Patients
Arm/Group Description	Patients receiving chemotherapy (Hydroxyurea, Alemtuzumab, Clofarabine, Melphalan), Hematopoietic Stem Cell Transplantation and radiation therapy (Total body Irradiation) mycophenylate mofetil and cyclosporine A. Clofarabine: days -7 through -3: 40 mg/m^2 intravenously over 2 hours Total body Irradiation: Administration of TBI: The dose of TBI will be 200 cGy given in a single fraction on day -1. The dose rate will be between 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus. Melphalan: day -2: 140 mg/m^2 intravenously over 30 minutes Hematopoietic Stem Cell Transplantation: receives infusion of stem cells on day 0 Alemtuzumab: 0.3 mg/kg intravenously (IV) days -12 through -8 mycophenylate mofetil: Day -3 through Day 30: 1 gram three times daily (total daily dose 3 grams/day) if the recipient is >50 kg, or 15 mg/kg three times daily if the recipient is ≤50 kg. The same dosage is used orally or intravenously.
All Cause Mortality
	Treated Patients
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treated Patients
	Affected / at Risk (%)	# Events
Total	10/38 (26.3%)
General disorders
Death Due to Disease Progression	2/38 (5.3%)
Disease Progression	4/38 (10.5%)
Graft Failure	4/38 (10.5%)
Infections and infestations
Infection with Grade 3 or 4 Neutrophils	1/38 (2.6%)
Other (Not Including Serious) Adverse Events
	Treated Patients
	Affected / at Risk (%)	# Events
Total	33/38 (86.8%)
Blood and lymphatic system disorders
Hemolytic Anemia	2/38 (5.3%)
Cardiac disorders
Pericardial Effusion	7/38 (18.4%)
Ear and labyrinth disorders
Requires Myringotomy, NOS	3/38 (7.9%)
Gastrointestinal disorders
Bloody Stool	2/38 (5.3%)
Pneumatosis Coli	2/38 (5.3%)
General disorders
Aseptic/Avascular Necrosis, NOS	2/38 (5.3%)
Requires Hemodialysis, NOS	2/38 (5.3%)
Hepatobiliary disorders
Veno-Oclusive Disease	2/38 (5.3%)
Infections and infestations
Bacterial Infection, Feces	10/38 (26.3%)
Bacterial Infection, Blood	12/38 (31.6%)
Pneumonia	14/38 (36.8%)
Fungal Infection, Skin	2/38 (5.3%)
Otitis Media	2/38 (5.3%)
Fungal Infection, Respiratory	3/38 (7.9%)
Viral Infection, Skin	3/38 (7.9%)
Sinusitis	3/38 (7.9%)
Upper Respiratory Infection	3/38 (7.9%)
Bacterial Infection, Skin	4/38 (10.5%)
Fungal Infection, Blood	4/38 (10.5%)
Viral Infection, Feces	4/38 (10.5%)
Bacterial Infection, Urine	5/38 (13.2%)
Viral Infection, Respiratory	6/38 (15.8%)
Viral Infection, Blood	7/38 (18.4%)
Metabolism and nutrition disorders
Hyperglycemia	3/38 (7.9%)
Nervous system disorders
Cerebral and Cerebellar Atrophy	2/38 (5.3%)
Neuropathy	2/38 (5.3%)
Seizures	8/38 (21.1%)
Renal and urinary disorders
Cystitis, NOS	5/38 (13.2%)
Reproductive system and breast disorders
Pulmonary Consolidation	2/38 (5.3%)
Respiratory, thoracic and mediastinal disorders
Respiratory Failure	2/38 (5.3%)
Pulmonary Opacities	3/38 (7.9%)
Requires Intubation, NOS	9/38 (23.7%)
Vascular disorders
Capillary Leak	2/38 (5.3%)
Hypertension	6/38 (15.8%)

Limitations/Caveats

Because the diseases being treated on this study are rare, our intent was to only report these outcomes in context with other protocols. The data was collected, but is not interpretable without combining the data with additional studies.

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.