Cyclophosphamide, Fludarabine, and Total-Body Irradiation Followed By Cellular Adoptive Immunotherapy, Autologous Stem Cell Transplantation, and Interleukin-2 in Treating Patients With Metastatic Melanoma

• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00096382
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 34
• Locations: 2
• Arms: 2
• Duration (Months): 52
• Patients Per Site: 17
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Biological therapies, such as cellular adoptive immunotherapy, work in different ways to stimulate the immune system and stop tumor cells from growing. Autologous stem cell transplant may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy. Interleukin-2 may stimulate a person's lymphocytes to kill tumor cells. Combining chemotherapy, radiation therapy, and biological therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cyclophosphamide and fludarabine together with radiation therapy followed by cellular adoptive immunotherapy, autologous stem cell transplant, and interleukin-2 works in treating patients with metastatic melanoma.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin)	Biological: aldesleukin; Biological: filgrastim; Biological: therapeutic tumor infiltrating lymphocytes; Drug: cyclophosphamide; Drug: fludarabine phosphate; Radiation: radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine complete clinical tumor regression in patients with metastatic melanoma treated with a myeloablative lymphoid-depleting preparative regimen comprising cyclophosphamide, fludarabine, and total body irradiation followed by autologous tumor-reactive tumor-infiltrating lymphocyte infusion, autologous CD34+ stem cell transplantation, and low-dose or high-dose interleukin-2.

• Evaluate the safety of this regimen in these patients.

Secondary

• Determine the survival of the infused lymphocytes by analyzing the sequence of the variable region of the T-cell receptor or flow cytometry in patients treated with this regimen.

OUTLINE:

• Autologous stem cell collection: Patients receive filgrastim (G-CSF) subcutaneously (SC) twice daily for 8 days. Beginning on day 5 of G-CSF, patients undergo apheresis daily for up to 3 days. Patients may receive 1 additional course of G-CSF and apheresis or use stem cells stored from a prior stem cell harvest in order to obtain an adequate number of cells.

• Lymphocyte-depleting myeloablative preparative regimen: Patients receive cyclophosphamide intravenous (IV) over 1 hour on days -5 and -6 and fludarabine IV over 15-30 minutes on days -6 to -2. Patients also undergo total body irradiation on day -1.

• Autologous lymphocyte infusion: Patients receive autologous tumor-reactive tumor-infiltrating lymphocytes IV over 20-30 minutes on day 0* followed by G-CSF SC once daily until blood counts recover.

• Autologous stem cell transplantation: Patients receive autologous CD34+ stem cells IV on day 2.

• Interleukin therapy: Patients are assigned to 1 of 2 cohorts, depending on whether they have received prior high-dose interleukin-2 (IL-2).

• Cohort 1 (patients who received prior high-dose IL-2): Beginning on day 0*, patients receive high-dose IL-2 IV over 15 minutes 3 times daily for up to 5 days (maximum of 15 doses).

• Cohort 3 (patients who have not received prior high-dose IL-2): Patients receive treatment as in cohort 1.

NOTE: *Day 0 is 1-4 days after the last dose of fludarabine.

Patients are evaluated at 4-6 weeks.

PROJECTED ACCRUAL: A total of 116 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment of Patients With Metastatic Melanoma Using a Transplant of Autologous Lymphocytes Reactive With Tumor Following a Myeloablative Lymphocyte Depleting Regimen of Chemotherapy, Total Body Irradiation and Reconstitution With CD34+ Cells
• Study Start Date: Sep 1, 2004
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Other: TBI 200cGy + TIL +HD IL-2, prior IL-2 Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator. Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.	Biological: aldesleukin; high dose: 720,000 IU/kg intravenously over 15 minutes every 8 hours for up to 5 days (maximum 5 doses) or low dose: 250,000 IU/kg subcutaneously daily for 5 days, after a two day rest, 125,000 IU/kg subcutaneously daily for 5 days for five weeks (2 days rest per week); Other Names: IL-2 Interleukin-2 ; Biological: filgrastim; 10 mcg/kg/day daily subcutaneously until neutrophil count >1x10^9/1.; Other Names: GCSF ; Biological: therapeutic tumor infiltrating lymphocytes; Lymphocytes that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.; Drug: cyclophosphamide; 60 mg/kg/day x 2 days intravenously over 1 hour; Other Names: Cytoxan ; Drug: fludarabine phosphate; 25 mg/m^2/day intravenous piggyback daily over 15-20 minutes for 5 days; Other Names: Fludara ; Radiation: radiation therapy; Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator.; Other Names: total body irradiation
Other: TBI 200cGy + TIL +HD IL-2, No prior IL-2 Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator. Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.	Biological: aldesleukin; high dose: 720,000 IU/kg intravenously over 15 minutes every 8 hours for up to 5 days (maximum 5 doses) or low dose: 250,000 IU/kg subcutaneously daily for 5 days, after a two day rest, 125,000 IU/kg subcutaneously daily for 5 days for five weeks (2 days rest per week); Other Names: IL-2 Interleukin-2 ; Biological: filgrastim; 10 mcg/kg/day daily subcutaneously until neutrophil count >1x10^9/1.; Other Names: GCSF ; Biological: therapeutic tumor infiltrating lymphocytes; Lymphocytes that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.; Drug: cyclophosphamide; 60 mg/kg/day x 2 days intravenously over 1 hour; Other Names: Cytoxan ; Drug: fludarabine phosphate; 25 mg/m^2/day intravenous piggyback daily over 15-20 minutes for 5 days; Other Names: Fludara ; Radiation: radiation therapy; Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator.; Other Names: total body irradiation

Outcome Measures

Primary Outcome Measures

1. Clinical Tumor Regression [Every 4-6 weeks for up to 1 year, and then every 6 months for up to 5 years.]

   Tumor regression is defined as a complete response (CR) or partial response (PR) and was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is the disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.

2. Safety [4 years]

   Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Diagnosis of metastatic melanoma

• Measurable disease

• Resected or stable brain metastases are allowed

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Eastern Cooperative Oncology Group (ECOG) 0-1

Life expectancy

• At least 3 months

Hematopoietic

• See Immunologic

• Absolute neutrophil count > 1,000/mm^3 (without support of filgrastim [G-CSF])

• Platelet count > 100,000/mm^3

• Hemoglobin ≥ 8 g/dL (transfusion allowed)

• No coagulation disorders

Hepatic

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 times upper limit of normal

• Bilirubin ≤ 2 mg/dL (< 3 mg/dL in patients with Gilbert's syndrome)

• No hepatitis B or C

Renal

• Creatinine ≤ 1.6 mg/dL

Cardiovascular

• Left ventricular ejection fraction (LVEF) ≥ 45% by cardiac stress test*

• No active major cardiovascular illness as evidenced by stress thallium or other comparable test

• No myocardial infarction

• No cardiac arrhythmias NOTE: *For patients ≥ 50 years of age receiving high-dose interleukin-2 (IL-2) OR patients with a history of electrocardiogram (EKG) abnormalities, symptoms of cardiac ischemia, or arrhythmias

Pulmonary

• Forced expiratory volume 1 (FEV_1) ≥ 60% of predicted by pulmonary function test in patients with prolonged history of cigarette smoking or symptoms of respiratory dysfunction*

• No active major respiratory illness

• No obstructive or restrictive pulmonary disease NOTE: *For patients receiving high-dose IL-2 only

Immunologic

• No active major immunologic illness

• No active systemic infections

• No primary or secondary immunodeficiency

• Fully recovered immune competence after prior chemotherapy or radiotherapy as evidenced by both of the following:

• Absolute neutrophil count > 1,000/mm^3

• No opportunistic infections

• Human Immunodeficiency virus (HIV) negative

• Epstein-Barr virus positive

Other

• Not pregnant or nursing

• Fertile patients must use effective contraception during and for 4 months after study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• At least 6 weeks since prior nitrosourea therapy

• No prior cyclophosphamide and fludarabine as part of a preparative regimen on National Cancer Institute (NCI) Surgery Branch adoptive cell therapy studies unless sufficient numbers of CD34+ stem cells (more than 2 x10^6/kg patient weight) have been obtained prior to the administration of chemotherapy

Endocrine therapy

• No concurrent systemic steroid therapy

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics

• Prior minor surgery within the past 3 weeks allowed if recovered

Other

• Recovered from all prior therapy

• At least 30 days since prior systemic therapy

• No other concurrent experimental agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland	United States	20892-1182
2	NCI - Surgery Branch	Bethesda	Maryland	United States	20892-1201

Sponsors and Collaborators

• National Institutes of Health Clinical Center (CC)
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Steven A. Rosenberg, MD, PhD, NCI - Surgery Branch

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Steven Rosenberg, M.D., Principal investigator, National Institutes of Health Clinical Center (CC)
• ClinicalTrials.gov Identifier: NCT00096382
• Other Study ID Numbers: 040288; 04-C-0288; NCI-7025; NCI-PRMC-P6273; CDR0000393480; NCT00092248
• First Posted: Nov 9, 2004
• Last Update Posted: Oct 28, 2015
• Last Verified: Sep 1, 2015

• Keywords provided by Steven Rosenberg, M.D., Principal investigator, National Institutes of Health Clinical Center (CC): stage IV melanoma; recurrent melanoma
• Additional relevant MeSH terms: Melanoma; Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Interleukin-2

Study Results

Participant Flow

Pre-assignment Detail	Of the 34 participants who were enrolled, 8 patients were not assigned to treatment since their TIL did not grow. Of the 26 assigned to treatment, 1 patient was not actually treated therefore only 25 patients were evaluable.

Arm/Group Title	TBI 200cGy + TIL +HD IL-2, Prior IL-2	TBI 200cGy + TIL +HD IL-2, No Prior IL-2
Arm/Group Description	Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator. Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.	Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator. Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.
Period Title: Overall Study
STARTED	23	3
COMPLETED	21	3
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	TBI 200cGy + TIL +HD IL-2, Prior IL-2	TBI 200cGy + TIL +HD IL-2, No Prior IL-2	Total
Arm/Group Description	Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator. Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.	Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator. Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.	Total of all reporting groups
Overall Participants	23	3	26
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	23 100%	3 100%	26 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.9 (9.6)	48.3 (12.0)	44.4 (9.7)
Sex: Female, Male (Count of Participants)
Female	8 34.8%	0 0%	8 30.8%
Male	15 65.2%	3 100%	18 69.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	23 100%	3 100%	26 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	23 100%	3 100%	26 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	23 100%	3 100%	26 100%

Outcome Measures

1. Primary Outcome

Title	Clinical Tumor Regression
Description	Tumor regression is defined as a complete response (CR) or partial response (PR) and was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is the disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.
Time Frame	Every 4-6 weeks for up to 1 year, and then every 6 months for up to 5 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TBI 200cGy + TIL +HD IL-2, Prior IL-2	TBI 200cGy + TIL +HD IL-2, No Prior IL-2
Arm/Group Description	Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator. Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.	Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator. Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.
Measure Participants	23	3
Complete Response	1 4.3%	1 33.3%
Partial Response	9 39.1%	2 66.7%

2. Primary Outcome

Title	Safety
Description	Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TBI 200cGy + TIL +HD IL-2, Prior IL-2	TBI 200cGy + TIL +HD IL-2, No Prior IL-2
Arm/Group Description	Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator. Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.	Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator. Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.
Measure Participants	23	3
Number [Participants]	23 100%	3 100%

Adverse Events

Arm/Group Title	TBI 200cGy + TIL +HD IL-2, Prior IL-2		TBI 200cGy + TIL +HD IL-2, No Prior IL-2
Arm/Group Description	Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator. Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.		Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator. Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.
All Cause Mortality
	TBI 200cGy + TIL +HD IL-2, Prior IL-2		TBI 200cGy + TIL +HD IL-2, No Prior IL-2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	TBI 200cGy + TIL +HD IL-2, Prior IL-2		TBI 200cGy + TIL +HD IL-2, No Prior IL-2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/22 (13.6%)		1/3 (33.3%)
Gastrointestinal disorders
Dehydration	1/22 (4.5%)	1	0/3 (0%)	0
General disorders
Fatigue	1/22 (4.5%)	1	0/3 (0%)	0
Infections and infestations
Infection	3/22 (13.6%)	3	0/3 (0%)	0
Nervous system disorders
Somnolence/depressed level of consciousness	1/22 (4.5%)	1	0/3 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/22 (4.5%)	1	0/3 (0%)	0
Hypoxia	1/22 (4.5%)	1	0/3 (0%)	0
Pneumonitis	1/22 (4.5%)	1	0/3 (0%)	0
Vascular disorders
Thrombosis	0/22 (0%)	0	1/3 (33.3%)	1
Other (Not Including Serious) Adverse Events
	TBI 200cGy + TIL +HD IL-2, Prior IL-2		TBI 200cGy + TIL +HD IL-2, No Prior IL-2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/22 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Hemoglobin	6/22 (27.3%)	6	1/3 (33.3%)	1
Leukocytes (total WBC)	17/22 (77.3%)	17	1/3 (33.3%)	1
Neutrophils/granulocytes (ANC/AGC)	21/22 (95.5%)	21	3/3 (100%)	3
Platelet	16/22 (72.7%)	16	3/3 (100%)	3
Edema: head and neck	1/22 (4.5%)	1	0/3 (0%)	0
Lymphopenia	22/22 (100%)	22	3/3 (100%)	3
PTT (partial thromboplastin time)	3/22 (13.6%)	3	3/3 (100%)	3
Cardiac disorders
Ventricular arrhythmia	1/22 (4.5%)	1	3/3 (100%)	3
Supraventricular & nodal arrhythmia	1/22 (4.5%)	1	3/3 (100%)	3
Vasovagal episode	1/22 (4.5%)	1	0/3 (0%)	0
Hypertension	1/22 (4.5%)	1	1/3 (33.3%)	1
Hypotension	8/22 (36.4%)	8	0/3 (0%)	0
Eye disorders
Retinopathy	0/22 (0%)	0	1/3 (33.3%)	1
Gastrointestinal disorders
Diarrhea	4/22 (18.2%)	4	1/3 (33.3%)	1
Distention, bloating, abdominal	1/22 (4.5%)	1	0/3 (0%)	0
Heartburn/Dyspepsia	1/22 (4.5%)	1	0/3 (0%)	0
Nausea	2/22 (9.1%)	2	0/3 (0%)	0
Vomiting	3/22 (13.6%)	3	0/3 (0%)	0
Hemorrhage, GI	1/22 (4.5%)	1	0/3 (0%)	0
General disorders
Rigors/Chills	2/22 (9.1%)	2	0/3 (0%)	0
Fatigue (asthenia, lethargy, malaise)	4/22 (18.2%)	4	0/3 (0%)	0
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	3/22 (13.6%)	3	2/3 (66.7%)	2
Insomnia	1/22 (4.5%)	1	0/3 (0%)	0
Weight loss	1/22 (4.5%)	1	0/3 (0%)	0
Pain	11/22 (50%)	11	0/3 (0%)	0
Infections and infestations
Febrile Neutropenia	9/22 (40.9%)	9	3/3 (100%)	3
Infection	5/22 (22.7%)	5	0/3 (0%)	0
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	9/22 (40.9%)	9	1/3 (33.3%)	1
ALT/SGPT (serum glutamic pyruvic transaminase)	2/22 (9.1%)	2	0/3 (0%)	0
AST/SGOT (serum glutamic oxaloacetic transaminase)	2/22 (9.1%)	2	0/3 (0%)	0
Bilirubin (hyperbilirubinemia)	2/22 (9.1%)	2	1/3 (33.3%)	1
Calcium, serum-low (hypocalcemia)	4/22 (18.2%)	4	1/3 (33.3%)	2
Creatinine	3/22 (13.6%)	3	0/3 (0%)	0
Magnesium, serum-high (hypermagnesemia)	2/22 (9.1%)	2	1/3 (33.3%)	1
Magnesium, serum-low (hypomagnesemia)	1/22 (4.5%)	1	1/3 (33.3%)	1
Phosphate, serum-low (hypophosphatemia)	3/22 (13.6%)	3	1/3 (33.3%)	2
Potassium, serum-high (hyperkalemia) increased	1/22 (4.5%)	1	0/3 (0%)	0
Potassium, serum-low (hypokalemia)	1/22 (4.5%)	1	0/3 (0%)	0
Sodium, serum-low (hyponatremia)	3/22 (13.6%)	3	1/3 (33.3%)	1
Uric acid	3/22 (13.6%)	3	0/3 (0%)	0
Nervous system disorders
Apnea	1/22 (4.5%)	1	0/3 (0%)	0
Leak, Cerebrospinal fluid (CSF)	1/22 (4.5%)	1	0/3 (0%)	0
Confusion	3/22 (13.6%)	3	1/3 (33.3%)	1
Dizziness	1/22 (4.5%)	1	0/3 (0%)	0
Somnolence/depressed level of consciousness	1/22 (4.5%)	1	0/3 (0%)	0
Syncope (fainting)	1/22 (4.5%)	1	0/3 (0%)	0
Tremor	1/22 (4.5%)	1	0/3 (0%)	0
Mood alteration	0/22 (0%)	0	1/3 (33.3%)	1
Renal and urinary disorders
Incontinence, urinary	1/22 (4.5%)	1	0/3 (0%)	0
Renal failure	1/22 (4.5%)	1	0/3 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory	2/22 (9.1%)	2	0/3 (0%)	0
Atelectasis	1/22 (4.5%)	1	0/3 (0%)	0
Cough	2/22 (9.1%)	2	0/3 (0%)	0
Dyspnea (shortness of breath)	13/22 (59.1%)	13	2/3 (66.7%)	2
Hypoxia	5/22 (22.7%)	5	1/3 (33.3%)	1
Pneumonitis/pulmonary infiltrates	1/22 (4.5%)	1	1/3 (33.3%)	1
Skin and subcutaneous tissue disorders
Hypopigmentation	2/22 (9.1%)	2	1/3 (33.3%)	1
Rash/Desquamation	2/22 (9.1%)	2	0/3 (0%)	0
Petechiae/purpura (hemorrhage/bleeding into skin or mucosa)	1/22 (4.5%)	1	0/3 (0%)	0
Vascular disorders
Acute vascular leak syndrome	1/22 (4.5%)	1	0/3 (0%)	0

Limitations/Caveats

[Not Specified]

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.