Allogeneic Bone Marrow Transplantation Using Less Intensive Therapy

• Sponsor: Masonic Cancer Center, University of Minnesota (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00303719
• Collaborator: (none)
• Enrollment: 342
• Location: 1
• Arms: 2
• Actual Duration (Months): 205.4
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

RATIONALE: A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy, or that have become cancer. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclophosphamide and fludarabine together with total-body irradiation followed by cyclosporine and mycophenolate mofetil before the transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with radiation therapy followed by cyclosporine and mycophenolate mofetil works in treating patients who are undergoing a donor stem cell transplant for hematologic cancer, metastatic breast cancer, or kidney cancer.

Condition or Disease	Intervention/Treatment	Phase
Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma; Plasma Cell Neoplasm; Myelodysplastic Syndromes	Biological: anti-thymocyte globulin; Drug: cyclophosphamide; Drug: cyclosporine; Drug: fludarabine; Drug: mycophenolate mofetil; Procedure: stem cell transplantation; Radiation: total body irradiation; Drug: filgrastim	Phase 2

Detailed Description

OBJECTIVES:

• Determine if a nonmyeloablative regimen comprising cyclophosphamide, fludarabine, and radiotherapy followed by cyclosporine and mycophenolate mofetil provides a prompt and durable donor engraftment in patients with hematologic malignancies or kidney cancer who are undergoing allogeneic stem cell transplantation.

• Determine the safety of this nonmyeloablative transplantation regimen in these patients.

• Determine the risk of graft-versus-host-disease in patients treated with this regimen.

• Determine the antineoplastic potency of nonmyeloablative stem cell transplantation in patients treated with this regimen.

• Determine the effect of lower doses of daily fludarabine on treatment-related mortality (TRM) OUTLINE: Patients are stratified according to risk (standard vs high).

• Preparative regimen*: Patients receive cyclophosphamide intravenously (IV) over 2 hours on day -6 and fludarabine IV over 1 hour on days -6 to -2. Patients undergo total body irradiation on day -1. Some patients also receive anti-thymocyte globulin (ATG)** IV every 12 hours on days -6 to -4. Patients who receive ATG* include the following:

• Related donor recipients who have not received combination chemotherapy within the past 6 months

• Unrelated donor recipients who have not received combination chemotherapy within the past 3 months

• Unrelated donor recipients who have received only 1 induction course for the treatment of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or blastic phase chronic myelogenous leukemia (CML) NOTE: **Patients who underwent prior autologous stem cell transplantation in the past year do not receive ATG.

• Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo allogeneic PBSCT on day 0.

• Graft-versus-host-disease prophylaxis: Patients receive cyclosporine IV over 2 hours beginning on day -3 and continuing until at least day 100. Patients also receive mycophenolate mofetil IV or orally twice daily on days -3 to 30.

• Donor lymphocyte infusion (DLI): Patients without active GVHD but deteriorating donor chimerism may receive DLI IV over 2 hours.

After completion of study treatment, patients are followed periodically for 2 years.

PROJECTED ACCRUAL: A total of 300 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 342 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Allogeneic Bone Marrow Transplantation Using Less Intensive Therapy
• Actual Study Start Date: Mar 26, 2002
• Actual Primary Completion Date: May 8, 2019
• Actual Study Completion Date: May 8, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: High Risk Patients Nonmyeloablative conditioning using fludarabine, cyclophosphamide and low dose Total Body Irradiation with or without anti-thymocyte globulin followed by allogeneic hematopoietic stem cell transplantation, immunosuppressive cyclosporine and mycophenolate mofetil and post-transplant use of bone marrow-stimulating filgrastim.	Biological: anti-thymocyte globulin; ATG dose is 15 mg/kg intravenous (IV) every 12 hours for 6 doses on days -6, -5, and -4. Those that should/will receive ATG in the preparative regimen: Related donor recipients who have not had exposure to combination chemotherapy in the 6 months preceding transplant should Unrelated donor recipients who have not had exposure to combination chemotherapy in the 3 months preceding transplant will Unrelated donor recipients who have had only a single induction cycle for the treatment of ALL/AML or MDS or CML blast crisis should Recipients with a prior autologous transplant in the year prior to second transplant do not require ATG.; Other Names: ATG ; Drug: cyclophosphamide; Cyclophosphamide will be given in a two hour infusion, total dose 50 mg/kg on day -6.; Other Names: Cytoxan ; Drug: cyclosporine; Patients will receive cyclosporine A (CSA) therapy beginning on day -3 maintaining a level of >200. For adults the initial dose will be 2.5 mg/kg IV over 2 hours every 12 hours. For children < 40 kg the initial dose will be 2.5 mg/kg IV over 2 hours every 8 hours. Patients will receive CSA until day +100.; Other Names: CSA ; Drug: fludarabine; Fludarabine 30 mg/m^2/day intravenous (IV) on day -6 through day -2., total dose 150 mg/m^2 for 5 days.; Other Names: Fludara ; Drug: mycophenolate mofetil; Mycophenolate mofetil (MMF) 1.5 gram twice a day (BID) or if < 50 kg will be given 15 mg/kg orally(po) BID,beginning on day -3, and discontinue at day +30 or 7 days after engraftment (3 consecutive days of absolute neutrophil count (ANC) > 0.5 x 109 /L).; Other Names: MMF ; Procedure: stem cell transplantation; On day 0, if related donor, stem cells are infused via central line. If unrelated donor, marrow/PBSC is infused after arrival and processing on day 0.; Other Names: peripheral blood stem cell transplantation bone marrow transplant ; Radiation: total body irradiation; The dose of TBI will be 200 cGy given in a single fraction on day -1.; Other Names: TBI ; Drug: filgrastim; Patients with white blood cell (WBC) counts < 2500 any time after stem cell infusion will be started on G-CSF support at Day +5 at a dose of 5 mcg/kg intravenously or subcutaneously (IV/SQ) daily rounded to vial size until absolute neutrophil count (ANC) > 2500 for 2 consecutive days.; Other Names: G-CSF
Experimental: Standard Risk Patients Nonmyeloablative conditioning using fludarabine, cyclophosphamide and low dose Total Body Irradiation with or without anti-thymocyte globulin followed by allogeneic hematopoietic stem cell transplantation, immunosuppressive cyclosporine and mycophenolate mofetil and post-transplant use of bone marrow-stimulating filgrastim.	Biological: anti-thymocyte globulin; ATG dose is 15 mg/kg intravenous (IV) every 12 hours for 6 doses on days -6, -5, and -4. Those that should/will receive ATG in the preparative regimen: Related donor recipients who have not had exposure to combination chemotherapy in the 6 months preceding transplant should Unrelated donor recipients who have not had exposure to combination chemotherapy in the 3 months preceding transplant will Unrelated donor recipients who have had only a single induction cycle for the treatment of ALL/AML or MDS or CML blast crisis should Recipients with a prior autologous transplant in the year prior to second transplant do not require ATG.; Other Names: ATG ; Drug: cyclophosphamide; Cyclophosphamide will be given in a two hour infusion, total dose 50 mg/kg on day -6.; Other Names: Cytoxan ; Drug: cyclosporine; Patients will receive cyclosporine A (CSA) therapy beginning on day -3 maintaining a level of >200. For adults the initial dose will be 2.5 mg/kg IV over 2 hours every 12 hours. For children < 40 kg the initial dose will be 2.5 mg/kg IV over 2 hours every 8 hours. Patients will receive CSA until day +100.; Other Names: CSA ; Drug: fludarabine; Fludarabine 30 mg/m^2/day intravenous (IV) on day -6 through day -2., total dose 150 mg/m^2 for 5 days.; Other Names: Fludara ; Drug: mycophenolate mofetil; Mycophenolate mofetil (MMF) 1.5 gram twice a day (BID) or if < 50 kg will be given 15 mg/kg orally(po) BID,beginning on day -3, and discontinue at day +30 or 7 days after engraftment (3 consecutive days of absolute neutrophil count (ANC) > 0.5 x 109 /L).; Other Names: MMF ; Procedure: stem cell transplantation; On day 0, if related donor, stem cells are infused via central line. If unrelated donor, marrow/PBSC is infused after arrival and processing on day 0.; Other Names: peripheral blood stem cell transplantation bone marrow transplant ; Radiation: total body irradiation; The dose of TBI will be 200 cGy given in a single fraction on day -1.; Other Names: TBI ; Drug: filgrastim; Patients with white blood cell (WBC) counts < 2500 any time after stem cell infusion will be started on G-CSF support at Day +5 at a dose of 5 mcg/kg intravenously or subcutaneously (IV/SQ) daily rounded to vial size until absolute neutrophil count (ANC) > 2500 for 2 consecutive days.; Other Names: G-CSF

Outcome Measures

Primary Outcome Measures

1. Neutrophil and Donor Cell Engraftment [Day 42 and Day 100]

   Successful sustained engraftment is defined as primary neutrophil engraftment by day 42 and e90% donor cells at day 100, with or without DLI. Engraftment based on absolute neutrophil count of donor origin > 0.5 x 10e9 /L for 3 days by day 42

Secondary Outcome Measures

1. Serious Adverse Events [Day 100]

   Safety by development of severe adverse events within 100 days of transplant

2. Transplant Related Mortality [Day 100]

   > 30% transplant related mortality at 100 days (non-relapse).

3. Overall Survival [1 year]

4. Acute Graft-Versus-Host Disease [Day 100]

   Grade III-IV graft versus host disease

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Standard patients will be enrolled into Arms 1-6. High risk patients (transplant with aplasia) will be considered separately in Arm 7.

• Age and Graft criteria (all patients)

• Patient's < or = 75 years old with a 5/6 or 6/6 related donor match are eligible.

• Patient's < or = 75 years who have a 7-8/8 HLA-A,B,C,DRB1 allele matched unrelated volunteer marrow and/or peripheral blood stem cell (PBSC) donor match are eligible.

• Disease Criteria (standard risk patients)

• Acute myelogenous leukemia

• Acute lymphocytic leukemia

• Chronic myelogenous leukemia all types except blast crisis (note treated blast crisis in chronic phase is eligible).

• Non-Hodgkins lymphoma (NHL), Hodgkins, chronic lymphocytic leukemia, multiple myeloma demonstrating chemosensitive disease

• Acquired bone marrow failure syndromes

• Myelodysplastic syndrome of all subtypes including refractory anemia (RA) or all IPSS categories if severe pancytopenia, transfusion requirements not responsive to therapy, or high risk cytogenetics. Blasts must be less than 5%. If >5% requires therapy (induction or Hypomethylating agents) pre-transplant to decrease disease burden.

• Renal cell cancer,

• Chronic myeloproliferative disorder, i.e. myelofibrosis

• Disease Criteria (High risk patients on Arm 7)

• Patients with refractory leukemia or MDS may be taken to transplant in aplasia after induction or re-induction chemotherapy or radiolabeled antibody. These high risk patients will be analyzed separately in Arm 7.

• Adequate organ function and performance status (all patients)

Exclusion Criteria:

• Pregnancy or breast feeding

• Evidence of HIV infection or known HIV positive serology

• Active serious infection

• Congenital bone marrow failure syndrome

• Previous irradiation that precludes the safe administration of an additional dose of 200 cGy of total body irradiation (TBI)

• Chronic myelogenous leukemia (CML) in refractory blast crisis

• Intermediate or high grade NHL, mantle cell NHL, and Hodgkins disease that is progressive on salvage therapy. Stable disease is acceptable to move forward provided it is non-bulky.

• Multiple Myeloma progressive on salvage chemotherapy.

DONOR ELIGIBILITY

• Related will undergo apheresis - if donor is unable to undergo apheresis, a bone marrow harvest is acceptable; unrelated volunteer donors must be able to undergo bone marrow harvest or apheresis.

• All donors must be able to give informed consent.

• Donors weighing less than 40 kg (children) will need evaluation by a pediatrician for suitability of the apheresis procedure. Informed consent must be obtained from parent or guardian as applicable for minors.

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: Erica Warlick, MD, Masonic Cancer Center, University of Minnesota

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 12, 2013

More Information

Additional Information:

• Related Info
• Related Info

Publications

• Warlick E, Ahn KW, Pedersen TL, Artz A, de Lima M, Pulsipher M, Akpek G, Aljurf M, Cahn JY, Cairo M, Chen YB, Cooper B, Deol A, Giralt S, Gupta V, Khoury HJ, Kohrt H, Lazarus HM, Lewis I, Olsson R, Pidala J, Savani BN, Seftel M, Socié G, Tallman M, Ustun C, Vij R, Vindeløv L, Weisdorf D. Reduced intensity conditioning is superior to nonmyeloablative conditioning for older chronic myelogenous leukemia patients undergoing hematopoietic cell transplant during the tyrosine kinase inhibitor era. Blood. 2012 Apr 26;119(17):4083-90. doi: 10.1182/blood-2012-02-409763. Epub 2012 Mar 9.
• Warlick ED, DeFor TE, Bejanyan N, Holtan S, MacMillan M, Blazar BR, Dusenbery K, Arora M, Bachanova V, Cooley S, Lazaryan A, McGlave P, Miller JS, Rashidi A, Slungaard A, Vercellotti G, Ustun C, Brunsein C, Weisdorf D. Reduced-Intensity Conditioning Followed by Related and Unrelated Allografts for Hematologic Malignancies: Expanded Analysis and Long-Term Follow-Up. Biol Blood Marrow Transplant. 2019 Jan;25(1):56-62. doi: 10.1016/j.bbmt.2018.07.038. Epub 2018 Aug 1.

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT00303719
• Other Study ID Numbers: 2001LS058; UMN-MT2001-10; 0108M06725
• First Posted: Mar 17, 2006
• Last Update Posted: May 12, 2020
• Last Verified: Apr 1, 2020

• Keywords provided by Masonic Cancer Center, University of Minnesota: leukemia; lymphoma; myeloma
• Additional relevant MeSH terms: Multiple Myeloma; Kidney Neoplasms; Neoplasms, Plasma Cell; Plasmacytoma; Myelodysplastic Syndromes; Cyclosporine; Mycophenolic Acid; Cyclophosphamide; Fludarabine; Cyclosporins; Antilymphocyte Serum

Study Results

Participant Flow

Arm/Group Title	High Risk Patients	Standard Risk Patients
Arm/Group Description	Patients with refractory leukemia or MDS	Patients with Disease criteria: Acute myelogenous leukemia , Acute lymphocytic leukemia, Chronic myelogenous leukemia , NHL, Hodgkins, chronic lymphocytic leukemia, multiple myeloma, Acquired bone marrow failure syndromes, Myelodysplastic syndrome, Renal cell cancer,Chronic myeloproliferative disorder
Period Title: Overall Study
STARTED	13	329
COMPLETED	13	292
NOT COMPLETED	0	37

Baseline Characteristics

Arm/Group Title	High Risk Patients	Standard Risk Patients	Total
Arm/Group Description	Patients with refractory leukemia or MDS	Patients with Disease criteria: Acute myelogenous leukemia , Acute lymphocytic leukemia, Chronic myelogenous leukemia , NHL, Hodgkins, chronic lymphocytic leukemia, multiple myeloma, Acquired bone marrow failure syndromes, Myelodysplastic syndrome, Renal cell cancer,Chronic myeloproliferative disorder	Total of all reporting groups
Overall Participants	13	292	305
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	4 30.8%	184 63%	188 61.6%
>=65 years	9 69.2%	108 37%	117 38.4%
Sex: Female, Male (Count of Participants)
Female	4 30.8%	112 38.4%	116 38%
Male	9 69.2%	180 61.6%	189 62%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 7.7%	3 1%	4 1.3%
Not Hispanic or Latino	10 76.9%	250 85.6%	260 85.2%
Unknown or Not Reported	2 15.4%	39 13.4%	41 13.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	2 0.7%	2 0.7%
Asian	0 0%	4 1.4%	4 1.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	5 1.7%	5 1.6%
White	12 92.3%	259 88.7%	271 88.9%
More than one race	0 0%	6 2.1%	6 2%
Unknown or Not Reported	1 7.7%	16 5.5%	17 5.6%

Outcome Measures

1. Primary Outcome

Title	Neutrophil and Donor Cell Engraftment
Description	Successful sustained engraftment is defined as primary neutrophil engraftment by day 42 and e90% donor cells at day 100, with or without DLI. Engraftment based on absolute neutrophil count of donor origin > 0.5 x 10e9 /L for 3 days by day 42
Time Frame	Day 42 and Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High Risk Patients	Standard Risk Patients
Arm/Group Description	Patients with refractory leukemia or MDS	Patients with Disease criteria: Acute myelogenous leukemia , Acute lymphocytic leukemia, Chronic myelogenous leukemia , NHL, Hodgkins, chronic lymphocytic leukemia, multiple myeloma, Acquired bone marrow failure syndromes, Myelodysplastic syndrome, Renal cell cancer,Chronic myeloproliferative disorder
Measure Participants	13	292
Count of Participants [Participants]	12 92.3%	289 99%

2. Secondary Outcome

Title	Serious Adverse Events
Description	Safety by development of severe adverse events within 100 days of transplant
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High Risk Patients	Standard Risk Patients
Arm/Group Description	Patients with refractory leukemia or MDS	Patients with Disease criteria: Acute myelogenous leukemia , Acute lymphocytic leukemia, Chronic myelogenous leukemia , NHL, Hodgkins, chronic lymphocytic leukemia, multiple myeloma, Acquired bone marrow failure syndromes, Myelodysplastic syndrome, Renal cell cancer,Chronic myeloproliferative disorder
Measure Participants	13	292
Count of Participants [Participants]	0 0%	47 16.1%

3. Secondary Outcome

Title	Transplant Related Mortality
Description	> 30% transplant related mortality at 100 days (non-relapse).
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High Risk Patients	Standard Risk Patients
Arm/Group Description	Patients with refractory leukemia or MDS	Patients with Disease criteria: Acute myelogenous leukemia , Acute lymphocytic leukemia, Chronic myelogenous leukemia , NHL, Hodgkins, chronic lymphocytic leukemia, multiple myeloma, Acquired bone marrow failure syndromes, Myelodysplastic syndrome,Chronic myeloproliferative disorder
Measure Participants	13	292
Count of Participants [Participants]	2 15.4%	40 13.7%

4. Secondary Outcome

Title	Overall Survival
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High Risk Patients	Standard Risk Patients
Arm/Group Description	Patients with refractory leukemia or MDS	Patients with Disease criteria: Acute myelogenous leukemia , Acute lymphocytic leukemia, Chronic myelogenous leukemia , NHL, Hodgkins, chronic lymphocytic leukemia, multiple myeloma, Acquired bone marrow failure syndromes, Myelodysplastic syndrome,Chronic myeloproliferative disorder
Measure Participants	13	292
Count of Participants [Participants]	8 61.5%	181 62%

5. Secondary Outcome

Title	Acute Graft-Versus-Host Disease
Description	Grade III-IV graft versus host disease
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High Risk Patients	Standard Risk Patients
Arm/Group Description	Patients with refractory leukemia or MDS	Patients with Disease criteria: Acute myelogenous leukemia , Acute lymphocytic leukemia, Chronic myelogenous leukemia , NHL, Hodgkins, chronic lymphocytic leukemia, multiple myeloma, Acquired bone marrow failure syndromes, Myelodysplastic syndrome, Renal cell cancer,Chronic myeloproliferative disorder
Measure Participants	13	292
Count of Participants [Participants]	2 15.4%	79 27.1%

Adverse Events

Time Frame	2 years
Arm/Group Title	High Risk Patients		Standard Risk Patients
Arm/Group Description	Patients with refractory leukemia or MDS		Patients with Disease criteria: Acute myelogenous leukemia , Acute lymphocytic leukemia, Chronic myelogenous leukemia , NHL, Hodgkins, chronic lymphocytic leukemia, multiple myeloma, Acquired bone marrow failure syndromes, Myelodysplastic syndrome, Renal cell cancer,Chronic myeloproliferative disorder
All Cause Mortality
	High Risk Patients		Standard Risk Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/13 (46.2%)		124/292 (42.5%)
Serious Adverse Events
	High Risk Patients		Standard Risk Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/13 (7.7%)		53/292 (18.2%)
Immune system disorders
Graft versus Host disease	0/13 (0%)		28/292 (9.6%)
Infections and infestations
Infection	0/13 (0%)		4/292 (1.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Relapse	1/13 (7.7%)		21/292 (7.2%)
Progressive disease	0/13 (0%)		0/292 (0%)
Other (Not Including Serious) Adverse Events
	High Risk Patients		Standard Risk Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/13 (92.3%)		272/292 (93.2%)
Cardiac disorders
Organ failure	2/13 (15.4%)	4	17/292 (5.8%)	21
Decrease cardiac function	0/13 (0%)	0	28/292 (9.6%)	33
pericardial effusion	2/13 (15.4%)	3	45/292 (15.4%)	51
Ear and labyrinth disorders
Ear disorder	2/13 (15.4%)	2	10/292 (3.4%)	10
Eye disorders
Eye disorder	0/13 (0%)	0	31/292 (10.6%)	48
Gastrointestinal disorders
Bleeding	2/13 (15.4%)	4	45/292 (15.4%)	56
General disorders
Other disorders	9/13 (69.2%)	25	179/292 (61.3%)	489
Hepatobiliary disorders
Abnormal liver	0/13 (0%)	0	18/292 (6.2%)	20
Infections and infestations
Bacterial infection	5/13 (38.5%)	15	128/292 (43.8%)	334
Infection (Etiology unknown)	4/13 (30.8%)	8	96/292 (32.9%)	219
Fungal infection	4/13 (30.8%)	15	122/292 (41.8%)	269
Pnemonia	8/13 (61.5%)	15	149/292 (51%)	351
Viral infection	8/13 (61.5%)	15	143/292 (49%)	291
Nervous system disorders
Neuropathy	1/13 (7.7%)	1	43/292 (14.7%)	51
Neurotoxicity	0/13 (0%)	0	29/292 (9.9%)	37
Renal and urinary disorders
Cystitis	1/13 (7.7%)	1	15/292 (5.1%)	18
Hemodialysis	2/13 (15.4%)	2	18/292 (6.2%)	21
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome (ARDS)	0/13 (0%)	0	17/292 (5.8%)	18
perihilar opacity	1/13 (7.7%)	1	14/292 (4.8%)	20
Increased oxygen requirement	1/13 (7.7%)	1	61/292 (20.9%)	73
Pulmonary hemorrhage	0/13 (0%)	0	25/292 (8.6%)	25

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.