Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia

• Sponsor: Masonic Cancer Center, University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT00258427
• Collaborator: (none)
• Enrollment: 14
• Location: 1
• Arms: 4
• Actual Duration (Months): 222.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: A bone marrow or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Giving combination chemotherapy before a donor stem cell transplant may make the transplant more likely to work. This may be an effective treatment for patients with high risk Fanconi's anemia.

PURPOSE: This clinical trial is studying how well combination chemotherapy works in treating high risk patients who are undergoing a donor stem cell transplant for Fanconi's anemia.

Condition or Disease	Intervention/Treatment	Phase
Fanconi Anemia	Biological: anti-thymocyte globulin; Biological: filgrastim; Drug: busulfan; Drug: cyclophosphamide; Drug: fludarabine phosphate; Drug: methylprednisolone; Biological: Hematopoietic stem cell transplantation	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine whether the incidence of neutrophil engraftment is acceptable in high-risk patients with Fanconi's anemia treated with busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin followed by allogeneic hematopoietic stem cell transplantation.

Secondary

• Determine the tolerability of mycophenolate mofetil in these patients.

• Determine the incidence of acute and chronic graft-vs-host disease in patients treated with this regimen.

• Determine the incidence of major infections in patients with a history of major infections treated with this regimen.

• Determine the incidence of relapse in patients with refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or acute myeloid leukemia treated with this regimen

• Determine the probability of 1-year survival of patients treated with this regimen.

OUTLINE: Patients are stratified according to donor/recipient HLA type (identical vs other).

• Cytoreductive combination chemotherapy: Patients receive busulfan intravenously (IV) over 2 hours twice daily on days -7 and -6 and cyclophosphamide IV over 2 hours and fludarabine IV over 30 minutes once daily on days -5 to -2.

• Graft failure prophylaxis: Patients receive methylprednisolone IV twice daily on days -5 to 30 and anti-thymocyte globulin IV over 4-6 hours twice daily on days -5 to -1.

• Graft-vs-host disease prophylaxis: Patients receive cyclosporine IV over 2 hours twice daily on days -3 to 100 (if patient has a matched sibling donor) or days -3 to 180 (if patient has another donor type). Patients also receive mycophenolate mofetil orally or IV twice daily on days -3 to 45.

• Allogeneic hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT (using bone marrow or umbilical cord blood) on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover.

After completion of study treatment, patients are followed periodically for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia MT2002-02
• Actual Study Start Date: Mar 26, 2002
• Actual Primary Completion Date: Oct 10, 2020
• Actual Study Completion Date: Oct 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Marrow Isolex Bone marrow processed using Isolex300i	Biological: anti-thymocyte globulin; Given 15 mg/kg/day intravenously every 12 hours on Days -5 through -1.; Other Names: ATG ; Biological: filgrastim; given 5 mcg/kg/day intravenously on Day 1 (continue until absolute neutrophil count (ANC) ≥2.5 x 10^9/L); Other Names: G-CSF ; Drug: busulfan; Busulfan 0.8 mg/kg intravenously (IV) every 12 hours on Days -7 and -6 (1.0 mg/kg IV if <4 years old); Other Names: Busulfex ; Drug: cyclophosphamide; 10 mg/kg intravenously (IV) on Days -5 through -2.; Other Names: Cytoxan ; Drug: fludarabine phosphate; 35 mg/m^2 intravenously (IV) on Days -5 through -2.; Other Names: Fludara ; Drug: methylprednisolone; 1 mg/kg intravenously (IV) every 12 hours on Days -5 through -1.; Other Names: Medrol ; Biological: Hematopoietic stem cell transplantation; Infused on Day 0 - Donor bone marrow or umbilical cord blood will be collected in the usual sterile manner using established parameters determined by the National Marrow Donor Program.; Other Names: HSCT
Experimental: USB arm No processing	Biological: anti-thymocyte globulin; Given 15 mg/kg/day intravenously every 12 hours on Days -5 through -1.; Other Names: ATG ; Biological: filgrastim; given 5 mcg/kg/day intravenously on Day 1 (continue until absolute neutrophil count (ANC) ≥2.5 x 10^9/L); Other Names: G-CSF ; Drug: busulfan; Busulfan 0.8 mg/kg intravenously (IV) every 12 hours on Days -7 and -6 (1.0 mg/kg IV if <4 years old); Other Names: Busulfex ; Drug: cyclophosphamide; 10 mg/kg intravenously (IV) on Days -5 through -2.; Other Names: Cytoxan ; Drug: fludarabine phosphate; 35 mg/m^2 intravenously (IV) on Days -5 through -2.; Other Names: Fludara ; Drug: methylprednisolone; 1 mg/kg intravenously (IV) every 12 hours on Days -5 through -1.; Other Names: Medrol ; Biological: Hematopoietic stem cell transplantation; Infused on Day 0 - Donor bone marrow or umbilical cord blood will be collected in the usual sterile manner using established parameters determined by the National Marrow Donor Program.; Other Names: HSCT
Experimental: Marrow Clinimacs Bone marrow processed using CliniMACS system	Biological: anti-thymocyte globulin; Given 15 mg/kg/day intravenously every 12 hours on Days -5 through -1.; Other Names: ATG ; Biological: filgrastim; given 5 mcg/kg/day intravenously on Day 1 (continue until absolute neutrophil count (ANC) ≥2.5 x 10^9/L); Other Names: G-CSF ; Drug: busulfan; Busulfan 0.8 mg/kg intravenously (IV) every 12 hours on Days -7 and -6 (1.0 mg/kg IV if <4 years old); Other Names: Busulfex ; Drug: cyclophosphamide; 10 mg/kg intravenously (IV) on Days -5 through -2.; Other Names: Cytoxan ; Drug: fludarabine phosphate; 35 mg/m^2 intravenously (IV) on Days -5 through -2.; Other Names: Fludara ; Drug: methylprednisolone; 1 mg/kg intravenously (IV) every 12 hours on Days -5 through -1.; Other Names: Medrol ; Biological: Hematopoietic stem cell transplantation; Infused on Day 0 - Donor bone marrow or umbilical cord blood will be collected in the usual sterile manner using established parameters determined by the National Marrow Donor Program.; Other Names: HSCT
Experimental: Sibling without CliniMacs Sibling donor without the use of CliniMACS system	Biological: anti-thymocyte globulin; Given 15 mg/kg/day intravenously every 12 hours on Days -5 through -1.; Other Names: ATG ; Biological: filgrastim; given 5 mcg/kg/day intravenously on Day 1 (continue until absolute neutrophil count (ANC) ≥2.5 x 10^9/L); Other Names: G-CSF ; Drug: busulfan; Busulfan 0.8 mg/kg intravenously (IV) every 12 hours on Days -7 and -6 (1.0 mg/kg IV if <4 years old); Other Names: Busulfex ; Drug: cyclophosphamide; 10 mg/kg intravenously (IV) on Days -5 through -2.; Other Names: Cytoxan ; Drug: fludarabine phosphate; 35 mg/m^2 intravenously (IV) on Days -5 through -2.; Other Names: Fludara ; Drug: methylprednisolone; 1 mg/kg intravenously (IV) every 12 hours on Days -5 through -1.; Other Names: Medrol ; Biological: Hematopoietic stem cell transplantation; Infused on Day 0 - Donor bone marrow or umbilical cord blood will be collected in the usual sterile manner using established parameters determined by the National Marrow Donor Program.; Other Names: HSCT

Outcome Measures

Primary Outcome Measures

1. Number of Participants Experiencing Graft Failure [Day 30]

   Graft failure is defined as absolute neutrophil count( ANC ) <5 x 10^8/L by day 30.

Secondary Outcome Measures

1. Number of Participants Experiencing Chronic Graft-Versus-Host Disease [Day 42]

   Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cellsinto a foreign host.

2. Number of Participants Experiencing Chronic Graft-Versus-Host Disease [1 year]

   Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cellsinto a foreign host.

3. Number of Participants Experiencing Acute Graft-Versus-Host Disease [1 year]

   Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.

4. Number of Participants Experiencing Acute Graft-Versus-Host Disease [Day 42]

   Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.

5. Number of Participants Experiencing Relapse [1 Year]

   Patients with leukemia will have this done by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate.

6. Number of Participants Experiencing Overall Survival [1 Year]

   Overall Survival - Number of patients alive at 1 year post transplant

7. Number of Participants Experiencing Major Infections [Day 1 through 1 year post-transplant]

   Number of participants experiencing Major Infections by the end of treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 44 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must be <45 years of age with a diagnosis of Fanconi anemia with:

• Biallelic BRCA2 mutations, or

• Aplastic anemia, or advanced myelodysplastic syndrome (MDS) (MDS with ≥5% blasts), or acute leukemia who are ineligible for total body irradiation. Aplastic anemia is defined as having at least one of the following (with or without cytogenetic abnormalities): platelet count <20 * 10^{9, - absolute neutrophil count (ANC) <5 * 10}8/L, - Hgb <8 g/dL

• Patients must have an HLA-A, B, DRB1 identical or 1 antigen mismatched related or unrelated BM donor or have an HLA-A, B, DRB1 identical, 1 antigen or 2 antigen mismatched related or unrelated umbilical cord blood (UCB) donor. Patients and donors will be typed for HLA-A and B using serological level typing and for DRB1 using high resolution molecular typing.

• Adequate major organ function including:

• Cardiac: ejection fraction >45%

• Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites, no cirrhosis)

• Karnofsky performance status >70% or Lansky >50%

• Women of child bearing potential must be using adequate birth control and have a negative pregnancy test.

Exclusion Criteria:

• Active CNS leukemia at time of HSCT.

• Active uncontrolled infection within one week of hematopoietic stem cell transplant (HSCT).

• Pregnant or lactating female.

Donor Inclusion Criteria:

• Donor must be in good health based on review of systems and results of physical examination.

• Donor must have a normal hemoglobin, white count, platelet count and partial thromboplastin time (PTT), and a negative diepoxybutane (DEB) test.

• HIV-NAT negative, HTLV-1, HTLV-2 negative, Hepatitis B and C negative.

• Female donors of childbearing potential must have a negative pregnancy test.

• Unrelated donors must agree to peripheral blood stem cell (PBSC) donation

Donor Exclusion Criteria:

• Donor is a lactating female.

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: Margaret MacMillan, MD, Masonic Cancer Center, University of Minnesota

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 4, 2019

More Information

Publications

None provided.

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT00258427
• Other Study ID Numbers: 2002LS014; MT2002-02; 0202M18741
• First Posted: Nov 24, 2005
• Last Update Posted: Dec 2, 2021
• Last Verified: Nov 1, 2021

• Keywords provided by Masonic Cancer Center, University of Minnesota: Fanconi anemia
• Additional relevant MeSH terms: Fanconi Syndrome; Anemia; Fanconi Anemia; Methylprednisolone; Cyclophosphamide; Busulfan; Fludarabine; Fludarabine phosphate; Antilymphocyte Serum

Study Results

Participant Flow

Arm/Group Title	Marrow Isolex	USB Arm	Marrow Clinimacs	Sibling withoutCliniMACS
Arm/Group Description	Bone marrow processed using Isolex300i	No processing	Bone marrow processed using CliniMACS	sibling donor without use of CliniMACS system
Period Title: Overall Study
STARTED	3	8	2	1
COMPLETED	3	8	2	1
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Marrow Isolex	USB Arm	Marrow Clinimacs	Sibling withoutCliniMACS	Total
Arm/Group Description	Bone marrow processed using Isolex300i	No processing	Bone marrow processed using CliniMACS	sibling donor without use of CliniMACS system	Total of all reporting groups
Overall Participants	3	8	2	1	14
Age (Count of Participants)
<=18 years	1 33.3%	8 100%	2 100%	1 100%	12 85.7%
Between 18 and 65 years	2 66.7%	0 0%	0 0%	0 0%	2 14.3%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	1 33.3%	3 37.5%	1 50%	0 0%	5 35.7%
Male	2 66.7%	5 62.5%	1 50%	1 100%	9 64.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	3 100%	8 100%	2 100%	1 100%	14 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	1 12.5%	0 0%	0 0%	1 7.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	3 37.5%	0 0%	0 0%	3 21.4%
White	3 100%	2 25%	2 100%	1 100%	8 57.1%
More than one race	0 0%	2 25%	0 0%	0 0%	2 14.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	3 100%	8 100%	2 100%	1 100%	14 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Experiencing Graft Failure
Description	Graft failure is defined as absolute neutrophil count( ANC ) <5 x 10^8/L by day 30.
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Marrow Isolex	USB Arm	Marrow Clinimacs	Sibling withoutCliniMACS
Arm/Group Description	Bone marrow processed using Isolex300i	No processing	Bone marrow processed using CliniMACS	sibling donor without use of CliniMACS system
Measure Participants	3	8	2	1
Count of Participants [Participants]	1 33.3%	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Number of Participants Experiencing Chronic Graft-Versus-Host Disease
Description	Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cellsinto a foreign host.
Time Frame	Day 42

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Marrow Isolex	USB Arm	Marrow Clinimacs	Sibling withoutCliniMACS
Arm/Group Description	Bone marrow processed using Isolex300i	No processing	Bone marrow processed using CliniMACS	sibling donor without use of CliniMACS system
Measure Participants	3	8	2	1
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

3. Secondary Outcome

Title	Number of Participants Experiencing Chronic Graft-Versus-Host Disease
Description	Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cellsinto a foreign host.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Marrow Isolex	USB Arm	Marrow Clinimacs	Sibling withoutCliniMACS
Arm/Group Description	Bone marrow processed using Isolex300i	No processing	Bone marrow processed using CliniMACS	sibling donor without use of CliniMACS system
Measure Participants	3	8	2	1
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

4. Secondary Outcome

Title	Number of Participants Experiencing Acute Graft-Versus-Host Disease
Description	Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Marrow Isolex	USB Arm	Marrow Clinimacs	Sibling withoutCliniMACS
Arm/Group Description	Bone marrow processed using Isolex300i	No processing	Bone marrow processed using CliniMACS	sibling donor without use of CliniMACS system
Measure Participants	3	8	2	1
Count of Participants [Participants]	0 0%	1 12.5%	0 0%	0 0%

5. Secondary Outcome

Title	Number of Participants Experiencing Acute Graft-Versus-Host Disease
Description	Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Time Frame	Day 42

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Marrow Isolex	USB Arm	Marrow Clinimacs	Sibling withoutCliniMACS
Arm/Group Description	Bone marrow processed using Isolex300i	No processing	Bone marrow processed using CliniMACS	sibling donor without use of CliniMACS system
Measure Participants	3	8	2	1
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

6. Secondary Outcome

Title	Number of Participants Experiencing Relapse
Description	Patients with leukemia will have this done by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate.
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Marrow Isolex	USB Arm	Marrow Clinimacs	Sibling withoutCliniMACS
Arm/Group Description	Bone marrow processed using Isolex300i	No processing	Bone marrow processed using CliniMACS	sibling donor without use of CliniMACS system
Measure Participants	3	8	2	1
Count of Participants [Participants]	0 0%	2 25%	1 50%	0 0%

7. Secondary Outcome

Title	Number of Participants Experiencing Overall Survival
Description	Overall Survival - Number of patients alive at 1 year post transplant
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Marrow Isolex	USB Arm	Marrow Clinimacs	Sibling withoutCliniMACS
Arm/Group Description	Bone marrow processed using Isolex300i	No processing	Bone marrow processed using CliniMACS	sibling donor without use of CliniMACS system
Measure Participants	3	8	2	1
Count of Participants [Participants]	1 33.3%	4 50%	1 50%	1 100%

8. Secondary Outcome

Title	Number of Participants Experiencing Major Infections
Description	Number of participants experiencing Major Infections by the end of treatment
Time Frame	Day 1 through 1 year post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Marrow Isolex	USB Arm	Marrow Clinimacs	Sibling withoutCliniMACS
Arm/Group Description	Bone marrow processed using Isolex300i	No processing	Bone marrow processed using CliniMACS	sibling donor without use of CliniMACS system
Measure Participants	3	8	2	1
Count of Participants [Participants]	3 100%	8 100%	2 100%	1 100%

Adverse Events

Time Frame	1 year
Arm/Group Title	Marrow Isolex		USB Arm		Marrow Clinimacs		Sibling withoutCliniMACS
Arm/Group Description	Bone marrow processed using Isolex300i		No processing		Bone marrow processed using CliniMACS		sibling donor without use of CliniMACS system
All Cause Mortality
	Marrow Isolex		USB Arm		Marrow Clinimacs		Sibling withoutCliniMACS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		4/8 (50%)		1/2 (50%)		0/1 (0%)
Serious Adverse Events
	Marrow Isolex		USB Arm		Marrow Clinimacs		Sibling withoutCliniMACS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		2/8 (25%)		1/2 (50%)		0/1 (0%)
General disorders
Primary Graft Failure	1/3 (33.3%)	1	0/8 (0%)	0	0/2 (0%)	0	0/1 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Death	2/3 (66.7%)	2	1/8 (12.5%)	1	0/2 (0%)	0	0/1 (0%)	0
Relapse	0/3 (0%)	0	0/8 (0%)	0	1/2 (50%)	1	0/1 (0%)	0
Respiratory, thoracic and mediastinal disorders
diffuse alveolar hemorrhage	0/3 (0%)	0	1/8 (12.5%)	1	0/2 (0%)	0	0/1 (0%)	0
Other (Not Including Serious) Adverse Events
	Marrow Isolex		USB Arm		Marrow Clinimacs		Sibling withoutCliniMACS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		7/8 (87.5%)		2/2 (100%)		1/1 (100%)
Blood and lymphatic system disorders
Coagulopathy	1/3 (33.3%)	1	0/8 (0%)	0	0/2 (0%)	0	0/1 (0%)	0
Disseminated intravascular coagulation	0/3 (0%)	0	1/8 (12.5%)	1	0/2 (0%)	0	0/1 (0%)	0
Cardiac disorders
pericardial effusion	0/3 (0%)	0	1/8 (12.5%)	2	0/2 (0%)	0	0/1 (0%)	0
Ear and labyrinth disorders
hearing loss	0/3 (0%)	0	0/8 (0%)	0	1/2 (50%)	1	0/1 (0%)	0
Gastrointestinal disorders
Eosinophilic gut	0/3 (0%)	0	1/8 (12.5%)	1	0/2 (0%)	0	0/1 (0%)	0
GI bleeding	1/3 (33.3%)	1	1/8 (12.5%)	1	0/2 (0%)	0	0/1 (0%)	0
Pneumoperitoneum	0/3 (0%)	0	1/8 (12.5%)	1	0/2 (0%)	0	0/1 (0%)	0
General disorders
Drug Rash with Eosinophilia	0/3 (0%)	0	1/8 (12.5%)	1	0/2 (0%)	0	0/1 (0%)	0
Engraftment syndrome	0/3 (0%)	0	2/8 (25%)	3	0/2 (0%)	0	0/1 (0%)	0
Primary Graft Failure	1/3 (33.3%)	1	0/8 (0%)	0	0/2 (0%)	0	0/1 (0%)	0
Hepatobiliary disorders
Veno occlusive disease	1/3 (33.3%)	1	2/8 (25%)	2	0/2 (0%)	0	0/1 (0%)	0
Infections and infestations
Infection	3/3 (100%)	18	6/8 (75%)	18	1/2 (50%)	1	1/1 (100%)	1
Pneumonia	1/3 (33.3%)	1	3/8 (37.5%)	10	1/2 (50%)	1	0/1 (0%)	0
Thrush	0/3 (0%)	0	0/8 (0%)	0	1/2 (50%)	1	0/1 (0%)	0
Nervous system disorders
Unresponsive	1/3 (33.3%)	1	0/8 (0%)	0	0/2 (0%)	0	0/1 (0%)	0
Renal and urinary disorders
Acute kidney injury	0/3 (0%)	0	2/8 (25%)	2	0/2 (0%)	0	0/1 (0%)	0
Dialysis	1/3 (33.3%)	1	1/8 (12.5%)	1	0/2 (0%)	0	0/1 (0%)	0
Renal failure	1/3 (33.3%)	1	1/8 (12.5%)	1	0/2 (0%)	0	0/1 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute hypoxic respiratory failure	0/3 (0%)	0	1/8 (12.5%)	1	0/2 (0%)	0	0/1 (0%)	0
acute respiratory distress syndrome	1/3 (33.3%)	1	0/8 (0%)	0	0/2 (0%)	0	0/1 (0%)	0
Intubation	2/3 (66.7%)	2	2/8 (25%)	2	0/2 (0%)	0	0/1 (0%)	0
pulmonary hemorrhage	0/3 (0%)	0	1/8 (12.5%)	1	0/2 (0%)	0	0/1 (0%)	0
Respiratory distress syndrome	0/3 (0%)	0	1/8 (12.5%)	1	0/2 (0%)	0	0/1 (0%)	0
Surgical and medical procedures
Chest Tube Placement	1/3 (33.3%)	1	1/8 (12.5%)	1	0/2 (0%)	0	0/1 (0%)	0
Chest Xray	0/3 (0%)	0	1/8 (12.5%)	1	0/2 (0%)	0	0/1 (0%)	0
Pleuracentesis	0/3 (0%)	0	1/8 (12.5%)	1	0/2 (0%)	0	0/1 (0%)	0
Vascular disorders
Hypertension	0/3 (0%)	0	2/8 (25%)	2	1/2 (50%)	1	1/1 (100%)	1

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.