Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Relapsed Germ Cell Cancer

• Sponsor: City of Hope Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00002931
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 48
• Location: 1
• Arm: 1
• Duration (Months): 213.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with bone marrow transplantation or peripheral stem cell transplantation works in treating patients with relapsed germ cell cancer.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors; Extragonadal Germ Cell Tumor; Ovarian Cancer; Teratoma; Testicular Germ Cell Tumor	Biological: filgrastim; Drug: carboplatin; Drug: etoposide; Drug: ifosfamide; Drug: paclitaxel; Procedure: autologous bone marrow transplantation; Procedure: bone marrow ablation with stem cell support	Phase 2

Detailed Description

OBJECTIVES:

• Estimate the antitumor activity of 2 courses of paclitaxel and carboplatin regimens with autologous stem cell rescue in patients with relapsed germ cell cancer.

• Evaluate the toxic effects of paclitaxel, carboplatin and etoposide (VP-16) with stem cell support followed by paclitaxel, carboplatin and ifosfamide with stem cell support in these patients.

OUTLINE: Patients receive filgrastim (G-CSF) SC or IV 4 days prior to peripheral blood stem cells (PBSC) apheresis. Autologous bone marrow harvest is performed when adequate stem cells cannot be collected.

Patients then receive course 1 of high-dose chemotherapy beginning on day -7 with paclitaxel IV over 24 hours. On days -6 to -4, patients receive etoposide IV over 2 hours and carboplatin (CBDCA) IV over 30 minutes 3 times daily. Following a 2 or 3 week recovery, a second course of chemotherapy begins on day -7, consisting of paclitaxel IV over 24 hours, then CBDCA and ifosfamide on days -6 to -4.

Reinfusion of PBSC and marrow begins on day -2 in both course 1 and 2. In addition, G-CSF IV is given twice a day until 3 consecutive postnadir days of granulocytes of at least 1000/mm^3 are maintained. On day 0, stem cells with or without bone marrow product are again administered.

Surgery may be performed after course 2 if indicated.

PROJECTED ACCRUAL: The expected accrual rate is 12 patients per year over 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Tandem High-Dose Chemotherapy With Autologous Stem Cell Rescue for Poor-Prognosis Germ Cell Cancer
• Study Start Date: Feb 1, 1997
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: HD Chemo and Auto Stem Cells

Biological: filgrastim; 5 ug/kg bid beginning 4 days prior to and continuing through stem cell collection.; Drug: carboplatin; AUC=7, daily X 3; Drug: etoposide; 20 mg/kg by 2 hours infusion daily X 3; Drug: ifosfamide; 3 gm/m2 IV over 30 minutes X 3 days; Drug: paclitaxel; 425 mg/m2 as 24 hour continuous infusion; Procedure: autologous bone marrow transplantation; Given in two divided infusions on day -2 and day 0; Procedure: bone marrow ablation with stem cell support; Two cycles of high dose chemotherapy followed by stem cell reinfusion

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [Until disease progression, up to 5 years.]

   Estimated using the product-limit method of Kaplan and Meier. Progression is defined as an increase o any radiologically measureable tumor by greater than 25% or a greater than 10% increase of elevated tumor markers.

2. Toxic Effects [From date of randomization until death of any cause, assessed up to 12 weeks]

   Number of Participants with Grade 3 and 4 Adverse Events Related to Protocol-based Therapy

Secondary Outcome Measures

1. Overall Survival [Until death from any cause, up to 5 years.]

   Estimated using the product-limit method of Kaplan and Meier.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Evaluable germ cell cancer (measurable by radiographic study and/or serum tumor marker elevation) and not curable by standard salvage therapy OR viable cancer on resection of post-chemotherapy residual masses in either intermediate or high risk category

• Bidimensionally measurable disease with measurements performed within 21 days of study entry

• Tumor marker (alpha-fetoprotein, lactate dehydrogenase, beta-human chorionic gonadotropin) studies performed within 7 days prior to study entry

PATIENT CHARACTERISTICS:

Age:

• 16 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3

• Platelet count at least 120,000/mm^3

• Hemoglobin at least 10 g/dL

Hepatic:

• Bilirubin no greater than 1.6 mg/dL

• SGOT and SGPT no greater than 2 times upper limit of normal (ULN)

• No active hepatitis or cirrhosis

Renal:

• Creatinine clearance at least 70 mL/min

Cardiovascular:

• Ejection fraction (MUGA or echocardiogram) normal

• No EKG evidence of active cardiac disease (arrhythmias, ischemia) which would contraindicate etoposide and paclitaxel study treatment

Pulmonary:

• PaO_2 at least 70 mm Hg

• FEV_1 at least 2 L or 75%

• No history of bleomycin associated or serious lung disease

Neurologic:

• No steroid or glucocorticoid treatment for patients with CNS metastatic disease; at least 1 month with stable post-radiotherapy neurological status and seizure free; if prior seizures, at least 1 month with therapeutic anticonvulsant levels prior to study

• Prior peripheral neuropathy requires consultation with principal investigator

Other:

• No significant active medical illness precluding study or survival

• Not HIV positive

• No prior malignancy within past 5 years except for adequately treated basal cell or squamous cell skin cancer

• No prior hematologic malignancies

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior bone marrow or stem cell rescue with high-dose chemotherapy

Chemotherapy:

• Prior chemotherapy allowed, excluding high-dose therapy with bone marrow or stem cell rescue

• No prior paclitaxel

Endocrine therapy:

• Not specified

Radiotherapy:

• No concurrent radiotherapy during study

Surgery:

• Recovered from prior surgery

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000

Sponsors and Collaborators

• City of Hope Medical Center
• National Cancer Institute (NCI)

Investigators

• Study Chair: Sumanta Pal, MD, City of Hope Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: City of Hope Medical Center
• ClinicalTrials.gov Identifier: NCT00002931
• Other Study ID Numbers: 96126; P30CA033572; CHNMC-96126; NCI-G97-1136; CDR0000065365
• First Posted: Jan 27, 2003
• Last Update Posted: Feb 23, 2017
• Last Verified: Jan 1, 2017

• Keywords provided by City of Hope Medical Center: recurrent malignant testicular germ cell tumor; testicular seminoma; testicular embryonal carcinoma; testicular choriocarcinoma; testicular yolk sac tumor; testicular embryonal carcinoma and teratoma; testicular embryonal carcinoma and teratoma with seminoma; testicular embryonal carcinoma and yolk sac tumor; testicular embryonal carcinoma and yolk sac tumor with seminoma; testicular embryonal carcinoma and seminoma; testicular yolk sac tumor and teratoma; testicular yolk sac tumor and teratoma with seminoma; testicular choriocarcinoma and yolk sac tumor; testicular choriocarcinoma and embryonal carcinoma; testicular choriocarcinoma and teratoma; testicular choriocarcinoma and seminoma; recurrent ovarian germ cell tumor; recurrent extragonadal non-seminomatous germ cell tumor; recurrent extragonadal seminoma; recurrent extragonadal germ cell tumor; adult teratoma; testicular immature teratoma; testicular mature teratoma; ovarian immature teratoma; ovarian mature teratoma; ovarian monodermal and highly specialized teratoma; stage III malignant testicular germ cell tumor; stage IV ovarian germ cell tumor; stage IV extragonadal non-seminomatous germ cell tumor; stage IV extragonadal seminoma; adult central nervous system germ cell tumor
• Additional relevant MeSH terms: Neoplasms; Neoplasms, Germ Cell and Embryonal; Nervous System Neoplasms; Central Nervous System Neoplasms; Teratoma; Paclitaxel; Etoposide; Carboplatin; Ifosfamide

Study Results

Participant Flow

Arm/Group Title	HD Chemo and Auto Stem Cells
Arm/Group Description	Cycle 1, stem cell mobilization with granulocyte-colony stimulating factor (G-CSF) at 10 μg/kg/d subcutaneously prior to leukapheresis. G-CSF administration daily during collection until the total collected product excelled 4 × 106 CD34+ cells/kg. 24-hour IV infusion of paclitaxel at 350 mg/m2 or 425 mg/m2 on day -7. Subsequent to this, patients receive etoposide (20 mg/kg IV over 2 hours) and carboplatin (AUC of 7 mg-min/mL IV over 30 minutes) daily on days -6, -5 and -4. IV infusion of 12.5% of the derived CD34+ stem cell product on day -2, followed by administration of 37.5% of the product on day 0. Cycle 2, comprised of paclitaxel, ifosfamide and carboplatin. Ifosfamide administered IV daily at 3 g/m2 over 30 minutes on days -6, -5 and -4. Mesna administered 24 hours subsequently as a 1 g/m2 bolus dose followed by 10g/m2 via continuous IV infusion over 72 hours. The derived CD34+ stem cell product administered in a manner identical to that during Cycle 1 on days -2 and 0.
Period Title: Overall Study
STARTED	48
COMPLETED	46
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	HD Chemo and Auto Stem Cells
Arm/Group Description	Cycle 1, stem cell mobilization with granulocyte-colony stimulating factor (G-CSF) at 10 μg/kg/d subcutaneously prior to leukapheresis. G-CSF administration daily during collection until the total collected product excelled 4 × 106 CD34+ cells/kg. 24-hour IV infusion of paclitaxel at 350 mg/m2 or 425 mg/m2 on day -7. Subsequent to this, patients receive etoposide (20 mg/kg IV over 2 hours) and carboplatin (AUC of 7 mg-min/mL IV over 30 minutes) daily on days -6, -5 and -4. IV infusion of 12.5% of the derived CD34+ stem cell product on day -2, followed by administration of 37.5% of the product on day 0. Cycle 2, comprised of paclitaxel, ifosfamide and carboplatin. Ifosfamide administered IV daily at 3 g/m2 over 30 minutes on days -6, -5 and -4. Mesna administered 24 hours subsequently as a 1 g/m2 bolus dose followed by 10g/m2 via continuous IV infusion over 72 hours. The derived CD34+ stem cell product administered in a manner identical to that during Cycle 1 on days -2 and 0.
Overall Participants	48
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	29
Gender (Count of Participants)
Female	1 2.1%
Male	47 97.9%
Region of Enrollment (participants) [Number]
United States	48 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	Estimated using the product-limit method of Kaplan and Meier. Progression is defined as an increase o any radiologically measureable tumor by greater than 25% or a greater than 10% increase of elevated tumor markers.
Time Frame	Until disease progression, up to 5 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HD Chemo and Auto Stem Cells
Arm/Group Description	Cycle 1, stem cell mobilization with granulocyte-colony stimulating factor (G-CSF) at 10 μg/kg/d subcutaneously prior to leukapheresis. G-CSF administration daily during collection until the total collected product excelled 4 × 106 CD34+ cells/kg. 24-hour IV infusion of paclitaxel at 350 mg/m2 or 425 mg/m2 on day -7. Subsequent to this, patients receive etoposide (20 mg/kg IV over 2 hours) and carboplatin (AUC of 7 mg-min/mL IV over 30 minutes) daily on days -6, -5 and -4. IV infusion of 12.5% of the derived CD34+ stem cell product on day -2, followed by administration of 37.5% of the product on day 0. Cycle 2, comprised of paclitaxel, ifosfamide and carboplatin. Ifosfamide administered IV daily at 3 g/m2 over 30 minutes on days -6, -5 and -4. Mesna administered 24 hours subsequently as a 1 g/m2 bolus dose followed by 10g/m2 via continuous IV infusion over 72 hours. The derived CD34+ stem cell product administered in a manner identical to that during Cycle 1 on days -2 and 0.
Measure Participants	48
Mean (95% Confidence Interval) [Months]	11.8

2. Primary Outcome

Title	Toxic Effects
Description	Number of Participants with Grade 3 and 4 Adverse Events Related to Protocol-based Therapy
Time Frame	From date of randomization until death of any cause, assessed up to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HD Chemo and Auto Stem Cells
Arm/Group Description	Cycle 1, stem cell mobilization with granulocyte-colony stimulating factor (G-CSF) at 10 μg/kg/d subcutaneously prior to leukapheresis. G-CSF administration daily during collection until the total collected product excelled 4 × 106 CD34+ cells/kg. 24-hour IV infusion of paclitaxel at 350 mg/m2 or 425 mg/m2 on day -7. Subsequent to this, patients receive etoposide (20 mg/kg IV over 2 hours) and carboplatin (AUC of 7 mg-min/mL IV over 30 minutes) daily on days -6, -5 and -4. IV infusion of 12.5% of the derived CD34+ stem cell product on day -2, followed by administration of 37.5% of the product on day 0. Cycle 2, comprised of paclitaxel, ifosfamide and carboplatin. Ifosfamide administered IV daily at 3 g/m2 over 30 minutes on days -6, -5 and -4. Mesna administered 24 hours subsequently as a 1 g/m2 bolus dose followed by 10g/m2 via continuous IV infusion over 72 hours. The derived CD34+ stem cell product administered in a manner identical to that during Cycle 1 on days -2 and 0.
Measure Participants	48
Hyperglycemia	4 8.3%
Transaminase alone	6 12.5%
Mucositis/stomatitis	10 20.8%
Nausea/vomiting	5 10.4%
Febrile neutropenia	1 2.1%
Diarrhea	3 6.3%
Hyperbilirubinemia	3 6.3%
Fever w/o neutropenia	2 4.2%
Hypocalcemia	2 4.2%
Hemorrhage	1 2.1%
Elevated INR/Prothrombin time	2 4.2%
Renal Failure	1 2.1%
Constipation	1 2.1%
Esophagitis	1 2.1%

3. Secondary Outcome

Title	Overall Survival
Description	Estimated using the product-limit method of Kaplan and Meier.
Time Frame	Until death from any cause, up to 5 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HD Chemo and Auto Stem Cells
Arm/Group Description	Cycle 1, stem cell mobilization with granulocyte-colony stimulating factor (G-CSF) at 10 μg/kg/d subcutaneously prior to leukapheresis. G-CSF administration daily during collection until the total collected product excelled 4 × 106 CD34+ cells/kg. 24-hour IV infusion of paclitaxel at 350 mg/m2 or 425 mg/m2 on day -7. Subsequent to this, patients receive etoposide (20 mg/kg IV over 2 hours) and carboplatin (AUC of 7 mg-min/mL IV over 30 minutes) daily on days -6, -5 and -4. IV infusion of 12.5% of the derived CD34+ stem cell product on day -2, followed by administration of 37.5% of the product on day 0. Cycle 2, comprised of paclitaxel, ifosfamide and carboplatin. Ifosfamide administered IV daily at 3 g/m2 over 30 minutes on days -6, -5 and -4. Mesna administered 24 hours subsequently as a 1 g/m2 bolus dose followed by 10g/m2 via continuous IV infusion over 72 hours. The derived CD34+ stem cell product administered in a manner identical to that during Cycle 1 on days -2 and 0.
Measure Participants	48
Median (95% Confidence Interval) [Months]	21.7

Adverse Events

Time Frame	Adverse events occurred over a period of 10 years and 6 months.
Adverse Event Reporting Description	"Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Arm/Group Title	HD Chemo and Auto Stem Cells
Arm/Group Description	Cycle 1, stem cell mobilization with granulocyte-colony stimulating factor (G-CSF) at 10 μg/kg/d subcutaneously prior to leukapheresis. G-CSF administration daily during collection until the total collected product excelled 4 × 106 CD34+ cells/kg. 24-hour IV infusion of paclitaxel at 350 mg/m2 or 425 mg/m2 on day -7. Subsequent to this, patients receive etoposide (20 mg/kg IV over 2 hours) and carboplatin (AUC of 7 mg-min/mL IV over 30 minutes) daily on days -6, -5 and -4. IV infusion of 12.5% of the derived CD34+ stem cell product on day -2, followed by administration of 37.5% of the product on day 0. Cycle 2, comprised of paclitaxel, ifosfamide and carboplatin. Ifosfamide administered IV daily at 3 g/m2 over 30 minutes on days -6, -5 and -4. Mesna administered 24 hours subsequently as a 1 g/m2 bolus dose followed by 10g/m2 via continuous IV infusion over 72 hours. The derived CD34+ stem cell product administered in a manner identical to that during Cycle 1 on days -2 and 0.
All Cause Mortality
	HD Chemo and Auto Stem Cells
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	HD Chemo and Auto Stem Cells
	Affected / at Risk (%)	# Events
Total	1/48 (2.1%)
Renal and urinary disorders
Renal failure	1/48 (2.1%)	1
Other (Not Including Serious) Adverse Events
	HD Chemo and Auto Stem Cells
	Affected / at Risk (%)	# Events
Total	46/48 (95.8%)
Blood and lymphatic system disorders
Clinical Coagulation	10/48 (20.8%)	13
Febrile neutropenia (ANC <1.0 x 10e9/L, fever >=38.5 degrees C)	12/48 (25%)	19
Transfusion: Platelets	1/48 (2.1%)	1
Transfusion: pRBCs	1/48 (2.1%)	1
Cardiac disorders
Dysrhythmias	9/48 (18.8%)	13
Ischemia	9/48 (18.8%)	13
Pericardial	9/48 (18.8%)	13
Cardiac ischemia/infarction	1/48 (2.1%)	1
EF/CHF	9/48 (18.8%)	13
Palpitations	1/48 (2.1%)	1
Supraventricular and nodal arrhythmia	19/48 (39.6%)	25
Ear and labyrinth disorders
Auditory/Ear - Other (Specify, __)	3/48 (6.3%)	6
Hearing	16/48 (33.3%)	21
Endocrine disorders
Cushingoid appearance (e.g., moon face, buffalo hump, centripetal obesity, cutaneous striae)	1/48 (2.1%)	1
Eye disorders
Dry eye syndrome	1/48 (2.1%)	1
Ocular/Visual - Other (Specify, __)	1/48 (2.1%)	4
Ophthalmoplegia/diplopia (double vision)	3/48 (6.3%)	3
Vision	16/48 (33.3%)	22
Vision-blurred vision	1/48 (2.1%)	1
Watery eye (epiphora, tearing)	1/48 (2.1%)	1
Gastrointestinal disorders
Hematemesis	3/48 (6.3%)	4
Stomatitis	16/48 (33.3%)	25
Stomatitis/pharyngitis (oral/pharyngeal mucositis) for BMT studies, if specified in the protocol.	1/48 (2.1%)	1
Colitis	1/48 (2.1%)	1
Constipation	28/48 (58.3%)	39
Diarrhea	41/48 (85.4%)	64
Diarrhea patients with a colostomy	2/48 (4.2%)	4
Esophagitis	2/48 (4.2%)	3
Gastritis (including bile reflux gastritis)	1/48 (2.1%)	1
Heartburn/dyspepsia	8/48 (16.7%)	9
Incontinence	2/48 (4.2%)	2
Melena/GI bleeding	3/48 (6.3%)	4
Mucositis/stomatitis (functional/symptomatic)	29/48 (60.4%)	45
Nausea	46/48 (95.8%)	74
Proctitis	2/48 (4.2%)	2
Vomiting	44/48 (91.7%)	73
General disorders
Clinical (Physical Exam)	13/48 (27.1%)	20
Fluid Retention	16/48 (33.3%)	25
Other Misc	14/48 (29.2%)	57
Edema	15/48 (31.3%)	16
Fatigue (asthenia, lethargy, malaise)	1/48 (2.1%)	1
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	18/48 (37.5%)	26
Fever (no infection)	15/48 (31.3%)	22
Injection site reaction/extravasation changes	2/48 (4.2%)	2
Pain - Other (Specify, __)	11/48 (22.9%)	13
Rigors/chills	17/48 (35.4%)	25
Hepatobiliary disorders
Hepatobiliary/Pancreas - Other (Specify, __)	2/48 (4.2%)	2
Immune system disorders
Allergy	16/48 (33.3%)	25
Infections and infestations
Infection	16/48 (33.3%)	25
Infection (documented clinically or microbiologically) with ANC <1.0 x 10e9/L	1/48 (2.1%)	1
Infection - Other (Specify, __)	1/48 (2.1%)	1
Infection with unknown ANC	2/48 (4.2%)	2
Infection without neutropenia	3/48 (6.3%)	4
Investigations
AGC	16/48 (33.3%)	25
ALT, SGPT (serum glutamic pyruvic transaminase)	27/48 (56.3%)	42
AST, SGOT(serum glutamic oxaloacetic transaminase)	27/48 (56.3%)	43
Alkaline Phosphatase	13/48 (27.1%)	20
Alkaline phosphatase	19/48 (39.6%)	24
Amylase	1/48 (2.1%)	1
Bilirubin	13/48 (27.1%)	20
Bilirubin (hyperbilirubinemia)	12/48 (25%)	15
Creatinine	26/48 (54.2%)	36
HGB/HCT	4/48 (8.3%)	5
INR (International Normalized Ratio of prothrombin time)	24/48 (50%)	38
Neutrophils (ANC) (Somlo COH)	7/48 (14.6%)	11
Neutrophils/granulocytes (ANC/AGC)	23/48 (47.9%)	39
PTT (Partial Thromboplastin Time)	16/48 (33.3%)	23
Partial Thromboplastin Time	10/48 (20.8%)	13
Platelets	38/48 (79.2%)	61
Platelets (Somlo COH)	7/48 (14.6%)	11
Prothrombin Time	10/48 (20.8%)	13
SGOT/SGT	13/48 (27.1%)	20
WBC	5/48 (10.4%)	7
Metabolism and nutrition disorders
Weight (Food Intake)	7/48 (14.6%)	12
Albumin, serum-low (hypoalbuminemia)	3/48 (6.3%)	5
Anorexia	13/48 (27.1%)	16
Calcium, serum-high (hypercalcemia)	3/48 (6.3%)	3
Calcium, serum-low (hypocalcemia)	29/48 (60.4%)	42
Glucose, serum-high (hyperglycemia)	30/48 (62.5%)	46
Glucose, serum-low (hypoglycemia)	2/48 (4.2%)	2
Hypercalcemia	14/48 (29.2%)	21
Hyperglycemia	15/48 (31.3%)	22
Hypocalcemia	14/48 (29.2%)	21
Hypoglycemia	15/48 (31.3%)	22
Hypomagnesemia	15/48 (31.3%)	22
Magnesium, serum-low (hypomagnesemia)	26/48 (54.2%)	39
Phosphate, serum-low (hypophosphatemia)	2/48 (4.2%)	3
Potassium, serum-low (hypokalemia)	2/48 (4.2%)	2
Sodium, serum-low (hyponatremia)	1/48 (2.1%)	2
Nervous system disorders
Cerebellar	15/48 (31.3%)	21
Cortical/State of Consciousness	16/48 (33.3%)	22
Dizziness	8/48 (16.7%)	9
Extrapyramidal/involuntary movement/restlessness	4/48 (8.3%)	4
Headache	16/48 (33.3%)	22
Motor Activity	15/48 (31.3%)	21
Neuropathy: motor	19/48 (39.6%)	24
Neuropathy: sensory	25/48 (52.1%)	37
Peripheral Nervous System Sensory	15/48 (31.3%)	21
Seizure	1/48 (2.1%)	1
Somnolence/depressed level of consciousness	6/48 (12.5%)	6
Speech impairment (e.g., dysphasia or aphasia)	1/48 (2.1%)	1
Syncope (fainting)	1/48 (2.1%)	1
Taste alteration (dysgeusia)	5/48 (10.4%)	5
Psychiatric disorders
Confusion	1/48 (2.1%)	1
Hallucinations	3/48 (6.3%)	3
Ideation	16/48 (33.3%)	22
Insomnia	16/48 (33.3%)	21
Mood	16/48 (33.3%)	22
Mood alteration	18/48 (37.5%)	21
Renal and urinary disorders
Hematuria	10/48 (20.8%)	15
Hematuria (in the absence of vaginal bleeding)	5/48 (10.4%)	6
Pain	22/48 (45.8%)	72
Proteinuria	11/48 (22.9%)	16
Urinary retention (including neurogenic bladder)	1/48 (2.1%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary	16/48 (33.3%)	25
Adult Respiratory Distress Syndrome (ARDS)	2/48 (4.2%)	2
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	1/48 (2.1%)	1
Cough	7/48 (14.6%)	7
Dyspnea (shortness of breath)	5/48 (10.4%)	5
Hemoptysis	3/48 (6.3%)	3
Hemorrhage, pulmonary/upper respiratory	7/48 (14.6%)	7
Hiccoughs (hiccups, singultus)	11/48 (22.9%)	16
Pulmonary/Upper Respiratory - Other (Specify, __)	2/48 (4.2%)	2
Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)	2/48 (4.2%)	2
Skin and subcutaneous tissue disorders
Rash/desquamation associated with GVHD for BMT studies	4/48 (8.3%)	5
Dermatology/Skin - Other (Specify, __)	10/48 (20.8%)	15
Extensive Skin Rash	13/48 (27.1%)	19
Local Skin Rash	13/48 (27.1%)	19
Rash/desquamation	17/48 (35.4%)	24
Sweating (diaphoresis)	2/48 (4.2%)	2
Vascular disorders
Hemorrhage	16/48 (33.3%)	25
Acute vascular leak syndrome	1/48 (2.1%)	1
Flushing	1/48 (2.1%)	1
Hemorrhage/Bleeding - Other (Specify, __)	9/48 (18.8%)	11
Hypertension	13/48 (27.1%)	17
Hypotension	19/48 (39.6%)	23

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.