Fludarabine, Cyclophosphamide, and Rituximab Versus Pentostatin, Cyclophosphamide, and Rituximab in Previously Untreated or Treated B-Cell Chronic Lymphocytic Leukemia Patients

• Sponsor: US Oncology Research (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00254163
• Collaborator: Astex Pharmaceuticals, Inc. (Industry)
• Enrollment: 184
• Locations: 11
• Arms: 2
• Duration (Months): 93
• Patients Per Site: 16.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this research study is to find out what effects (good and bad) the combination of Nipent+Cytoxan+Rituxan has on CLL cancer compared to Fludara+Cytoxan+Rituxan. While all of these drugs are approved by the Food and Drug Administration (FDA) for the treatment of other cancers, these combinations are experimental for the treatment of CLL.

Condition or Disease	Intervention/Treatment	Phase
B-Cell Chronic Lymphocytic Leukemia	Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Rituximab; Drug: Pentostatin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 184 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Randomized, Open Label, Phase III Trial of Fludarabine, Cyclophosphamide, and Rituximab vs. Pentostatin, Cyclophosphamide, and Rituximab in Previously Untreated or Treated B-cell Chronic Lymphocytic Leukemia
• Study Start Date: Dec 1, 2003
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Fludarabine, Cyclophosphamide, and Rituximab Fludarabine, Cyclophosphamide, and Rituximab (dosage based on day in cycle)	Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Rituximab
Experimental: Pentostatin, Cyclophosphamide, and Rituximab Pentostatin, Cyclophosphamide, and Rituximab (dosage depends on day in cycle)	Drug: Cyclophosphamide; Drug: Rituximab; Drug: Pentostatin; Other Names: Nipent

Outcome Measures

Primary Outcome Measures

1. Infection Rate [6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity]

   infection=febrile events requiring treatment

Secondary Outcome Measures

1. Infective Event Rate [6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity]

   infective events=temperature >101 without symptoms or temp <101 with symptoms

2. Percentage of Patients Hospitalized [6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity]

   Percentage of patients who were hospitalized due to any reasons during the study period.

3. Hematologic Recovery [2 months post-treatment]

   defined as Hb >11g/dL and a platelet count >100 × 10^3/mm^3

4. Mean Absolute Neutrophil Count (ANC) at Post-treatment [2 months post-treatment]

   mean Absolute Neutrophil Count (ANC) measured 2 months (8-10 weeks) following the last dose of study treatment

5. Complete Remission (CR) [6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity]

   Definitions of response is evaluated using guidelines proposed by the National Cancer Institute-Sponsored Working Group for Chronic Lymphocytic Leukemia. Complete remission (CR) requires all of the following for a period of at least 2 months: Absence of lymphadenopathy by physical examination and appropriate radiographic techniques. Lymph nodes must be <1 cm. No evidence of hepatomegaly or splenomegaly. Absence of constitutional symptoms. Normal CBC as exhibited by: Polymorphonuclear leukocytes ≥ 1,500/mm^3 Platelets > 100,000/mm^3 Hemoglobin > 11.0 g/dL (untransfused) Bone marrow aspirate and biopsy should be performed 2 months after clinical and laboratory results demonstrate that all of the requirements listed in 1-4 have been met to demonstrate that a CR has been achieved. The marrow sample must be at least normocellular for age, with less than 30% of the nucleated cells being lymphocytes. Lymphoid nodules should be absent.

6. Objective Remission Rate (ORR) [6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity]

   Complete remission (CR) see Outcome Measure 6. Partial remission (PR) must exhibit criteria 1 and 2 as well as one or more of the remaining features for at least 2 months. ≥50% decrease in peripheral blood lymphocyte count from the pretreatment baseline value. ≥50% reduction in lymphadenopathy. ≥50% reduction in the size of the liver and/or spleen. Polymorphonuclear leukocytes ≥ 1,500/mm^3 or 50% improvement over baseline. Platelets >100,000/mm^3 or 50% improvement over baseline. Hemoglobin >11.0 g/dL or 50% improvement over baseline without transfusions. Nodular partial remission (nPR) is defined as a CR with persistent bone marrow nodules; Objective Remission (OR) = CR + PR + nPR.

7. Progression-free Survival (PFS) Rate at 1-year [12 months after registered.]

   PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date

8. Progression-free Survival (PFS) Rate at 2-year [24 months after registered.]

   PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date.

Eligibility Criteria

Criteria

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

INCLUSION CRITERIA:

Patients will be eligible for inclusion in this study if they meet all of the following criteria:

• Progressive, histologically proven B-cell CLL.

• Stage II, III, or IV B-cell CLL, as defined by Appendix III.

Note: The pathology or flow cytometry (of peripheral blood or a bone marrow) report, done by the local laboratory which documents these findings, must be included in the source documents. The SI must review the above pathology report or flow cytometry report results (including bone marrow aspirate analysis and CD5 and CD20 results) by fax, prior to registration, to confirm each patient's eligibility. Results should be consistent with typical B-cell CLL. If Dr. Reynolds is not available to review these documents, they must be reviewed by Dr. Nicholas J. Di Bella.

• Patient must be CD20 +

• Patient must be CD5+ (CD5 >70%)

• No more than 1 prior course (regimen) of chemotherapy, which can include Fludara or Rituxan

• No prior radiation therapy, except for the treatment of skin cancer or a nonmalignant condition.

• If patient has lymph node involvement, a CT scan confirming measurable tumor size (lymph node must be >1 cm in its longest transverse diameter).

• SI has been notified IF patient is on replacement steroids at time of registration.

• Age greater than 18 years.

• ECOG performance status of 0-2 (Appendix I).

• Normal renal function (creatinine <1.5 mg/dL and BUN <25 mg/dL).

• Absolute neutrophil count (ANC) greater than 1,000 cells/µL, platelet count greater than 50,000 cells/µL, and hemoglobin greater than 9 g/dL.

• Bilirubin less than 2.0 mg/dL, and AST and ALT less than 5 times the upper limit of normal.

• Negative serum pregnancy test within 7 days prior to registration (female patients of childbearing potential).

• Agrees to use an acceptable method of birth control, if fertile patient (male or female), to avoid pregnancy for the duration of the study and for at least 3 months thereafter.

• A signed Patient Informed Consent Form has been obtained.

• A signed Patient Authorization Form has been obtained.

EXCLUSION CRITERIA:

Patients will be excluded from this study if they meet any of the following criteria:

• Any disease other than histologically confirmed progressive, Stage II, III, or IV CLL.

• Well differentiated lymphocytic lymphoma in nodes without lymphocytosis.

• More than 1 prior course (regimen) of chemotherapy.

• Any radiation for the treatment of CLL.

• Any prior Nipent.

• Known to be CD20 negative (CD20 <20%).

• Pregnant or lactating, or has a positive pregnancy test.

• Has a history of other malignancy (other than in situ cervical cancer, carcinoma intraepithelial neoplasia, or non-melanoma skin cancer) within the last 5 years, which could affect the administration of these study drugs or assessment of current CLL.

• Known to be HIV positive.

• Uncontrolled thyroid disease or uncontrolled abnormal thyroid function.

Note: Patients with thyroid disease that is controlled with medication may participate.

• A history of recent, unstable organic heart disease or stable organic heart disease with LVEF <50%.

• A known hypersensitivity to Fludara, Nipent, Rituxan, or Cytoxan, or any component of these drugs.

• Autoimmune hemolytic anemia.

• Unable to comply with requirements of study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cancer Centers of Florida, P.A.	Ocoee	Florida	United States	34761
2	Hope Center	Terre Haute	Indiana	United States	47802
3	Alliance Hematology Oncology PA	Westminster	Maryland	United States	21157
4	St Joseph Oncology, Inc	St Joseph	Missouri	United States	64507
5	New York Oncology Hematology, PC	Albany	New York	United States	12208
6	Northwestern Carolina Oncology Hemato	Hickory	North Carolina	United States	28602
7	Medical Oncology Associates	Kingston	Pennsylvania	United States	18704
8	South Texas Cancer Center-McAllen	McAllen	Texas	United States	78503
9	Texas Oncology Cancer Center-Sugar Land	Sugar Land	Texas	United States	77479
10	Cancer Care Northwest-South	Spokane	Washington	United States	99202
11	Yakima Valley Mem Hosp/North Star Lodge	Yakima	Washington	United States	98902

Sponsors and Collaborators

• US Oncology Research
• Astex Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Craig Reynolds, MD, US Oncology Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: US Oncology Research
• ClinicalTrials.gov Identifier: NCT00254163
• Other Study ID Numbers: 03017; NIP-03-007
• First Posted: Nov 15, 2005
• Last Update Posted: Nov 3, 2016
• Last Verified: Sep 1, 2016

• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Cyclophosphamide; Rituximab; Fludarabine; Pentostatin

Study Results

Participant Flow

Arm/Group Title	FCR Arm	PCR Arm
Arm/Group Description	Fludarabine, Cyclophosphamide, and Rituximab	Pentostatin, Cyclophosphamide, and Rituximab
Period Title: Overall Study
STARTED	92	92
COMPLETED	47	46
NOT COMPLETED	45	46

Baseline Characteristics

Arm/Group Title	FCR Arm	PCR Arm	Total
Arm/Group Description	Fludarabine, Cyclophosphamide, and Rituximab	Pentostatin, Cyclophosphamide, and Rituximab	Total of all reporting groups
Overall Participants	92	92	184
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.3 (10.2)	63.6 (9.9)	63.5 (10.0)
Sex: Female, Male (Count of Participants)
Female	27 29.3%	22 23.9%	49 26.6%
Male	65 70.7%	70 76.1%	135 73.4%
Race/Ethnicity, Customized (participants) [Number]
Caucasion	81 88%	84 91.3%	165 89.7%
Black	7 7.6%	5 5.4%	12 6.5%
Hispanic	2 2.2%	3 3.3%	5 2.7%
Mixed: Black/Indian	2 2.2%	0 0%	2 1.1%
Region of Enrollment (participants) [Number]
United States	92 100%	92 100%	184 100%

Outcome Measures

1. Primary Outcome

Title	Infection Rate
Description	infection=febrile events requiring treatment
Time Frame	6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	FCR Arm	PCR Arm
Arm/Group Description	Fludarabine, Cyclophosphamide, and Rituximab	Pentostatin, Cyclophosphamide, and Rituximab
Measure Participants	86	85
Number (95% Confidence Interval) [percentage of participants]	31.4 34.1%	36.5 39.7%

2. Secondary Outcome

Title	Infective Event Rate
Description	infective events=temperature >101 without symptoms or temp <101 with symptoms
Time Frame	6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	FCR Arm	PCR Arm
Arm/Group Description	Fludarabine, Cyclophosphamide, and Rituximab	Pentostatin, Cyclophosphamide, and Rituximab
Measure Participants	86	85
Number [percentage of infective events]	38	45

3. Secondary Outcome

Title	Percentage of Patients Hospitalized
Description	Percentage of patients who were hospitalized due to any reasons during the study period.
Time Frame	6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	FCR Arm	PCR Arm
Arm/Group Description	Fludarabine, Cyclophosphamide, and Rituximab	Pentostatin, Cyclophosphamide, and Rituximab
Measure Participants	86	85
Number [percentage of participants]	35 38%	43.5 47.3%

4. Secondary Outcome

Title	Hematologic Recovery
Description	defined as Hb >11g/dL and a platelet count >100 × 10^3/mm^3
Time Frame	2 months post-treatment

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	FCR Arm	PCR Arm
Arm/Group Description	Fludarabine, Cyclophosphamide, and Rituximab	Pentostatin, Cyclophosphamide, and Rituximab
Measure Participants	86	85
Number (95% Confidence Interval) [percentage of participants]	3.5 3.8%	14.1 15.3%

5. Secondary Outcome

Title	Mean Absolute Neutrophil Count (ANC) at Post-treatment
Description	mean Absolute Neutrophil Count (ANC) measured 2 months (8-10 weeks) following the last dose of study treatment
Time Frame	2 months post-treatment

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	FCR Arm	PCR Arm
Arm/Group Description	Fludarabine, Cyclophosphamide, and Rituximab	Pentostatin, Cyclophosphamide, and Rituximab
Measure Participants	86	85
Mean (Standard Deviation) [10^3 cells/mm^3]	1.7 (0.9)	2.2 (1.6)

6. Secondary Outcome

Title	Complete Remission (CR)
Description	Definitions of response is evaluated using guidelines proposed by the National Cancer Institute-Sponsored Working Group for Chronic Lymphocytic Leukemia. Complete remission (CR) requires all of the following for a period of at least 2 months: Absence of lymphadenopathy by physical examination and appropriate radiographic techniques. Lymph nodes must be <1 cm. No evidence of hepatomegaly or splenomegaly. Absence of constitutional symptoms. Normal CBC as exhibited by: Polymorphonuclear leukocytes ≥ 1,500/mm^3 Platelets > 100,000/mm^3 Hemoglobin > 11.0 g/dL (untransfused) Bone marrow aspirate and biopsy should be performed 2 months after clinical and laboratory results demonstrate that all of the requirements listed in 1-4 have been met to demonstrate that a CR has been achieved. The marrow sample must be at least normocellular for age, with less than 30% of the nucleated cells being lymphocytes. Lymphoid nodules should be absent.
Time Frame	6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	FCR Arm	PCR Arm
Arm/Group Description	Fludarabine, Cyclophosphamide, and Rituximab	Pentostatin, Cyclophosphamide, and Rituximab
Measure Participants	86	85
Number (95% Confidence Interval) [percentage of participants]	14.0 15.2%	7.1 7.7%

7. Secondary Outcome

Title	Objective Remission Rate (ORR)
Description	Complete remission (CR) see Outcome Measure 6. Partial remission (PR) must exhibit criteria 1 and 2 as well as one or more of the remaining features for at least 2 months. ≥50% decrease in peripheral blood lymphocyte count from the pretreatment baseline value. ≥50% reduction in lymphadenopathy. ≥50% reduction in the size of the liver and/or spleen. Polymorphonuclear leukocytes ≥ 1,500/mm^3 or 50% improvement over baseline. Platelets >100,000/mm^3 or 50% improvement over baseline. Hemoglobin >11.0 g/dL or 50% improvement over baseline without transfusions. Nodular partial remission (nPR) is defined as a CR with persistent bone marrow nodules; Objective Remission (OR) = CR + PR + nPR.
Time Frame	6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	FCR Arm	PCR Arm
Arm/Group Description	Fludarabine, Cyclophosphamide, and Rituximab	Pentostatin, Cyclophosphamide, and Rituximab
Measure Participants	86	85
Number (95% Confidence Interval) [percentage of participants]	59.3 64.5%	49.4 53.7%

8. Secondary Outcome

Title	Progression-free Survival (PFS) Rate at 1-year
Description	PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date
Time Frame	12 months after registered.

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	FCR Arm	PCR Arm
Arm/Group Description	Fludarabine, Cyclophosphamide, and Rituximab	Pentostatin, Cyclophosphamide, and Rituximab
Measure Participants	86	85
Number (95% Confidence Interval) [probability of Progression-free Survival]	0.86	0.84

9. Secondary Outcome

Title	Progression-free Survival (PFS) Rate at 2-year
Description	PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date.
Time Frame	24 months after registered.

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	FCR Arm	PCR Arm
Arm/Group Description	Fludarabine, Cyclophosphamide, and Rituximab	Pentostatin, Cyclophosphamide, and Rituximab
Measure Participants	86	85
Number (95% Confidence Interval) [Probability of Progression-free Survival]	0.72	0.63

Adverse Events

Time Frame	During the whole treatment period, up to 30 days following last dose.
Adverse Event Reporting Description	The safety population, which received at least one of study treatment, was included in the analysis of adverse event. Patients included in this study were 88 and 89 in FCR arm and PCR arm, respectively.
Arm/Group Title	FCR Arm		PCR Arm
Arm/Group Description	Fludarabine, Cyclophosphamide, and Rituximab		Pentostatin, Cyclophosphamide, and Rituximab
All Cause Mortality
	FCR Arm		PCR Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	FCR Arm		PCR Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/88 (20.5%)		22/89 (24.7%)
Blood and lymphatic system disorders
ANEMIA	1/88 (1.1%)	1	1/89 (1.1%)	1
EDEMA	0/88 (0%)	0	1/89 (1.1%)	1
FEBRILE NEUTROPENIA	5/88 (5.7%)	5	5/89 (5.6%)	5
NEUTROPENIA	4/88 (4.5%)	4	4/89 (4.5%)	4
PANCYTOPENIA	0/88 (0%)	0	1/89 (1.1%)	1
Cardiac disorders
CARDIOVASC DIS	0/88 (0%)	0	1/89 (1.1%)	1
HEART FAIL RIGHT	0/88 (0%)	0	1/89 (1.1%)	1
TACHYCARDIA	0/88 (0%)	0	1/89 (1.1%)	1
Gastrointestinal disorders
ABDO ENLARGE	1/88 (1.1%)	1	0/89 (0%)	0
COLITIS	0/88 (0%)	0	1/89 (1.1%)	1
DEHYDRAT	0/88 (0%)	0	3/89 (3.4%)	3
DIARRHEA	1/88 (1.1%)	1	0/89 (0%)	0
PAIN ABDO	0/88 (0%)	0	1/89 (1.1%)	1
STOMATITIS	1/88 (1.1%)	1	0/89 (0%)	0
VOMIT	1/88 (1.1%)	1	0/89 (0%)	0
General disorders
CHEST PAIN	0/88 (0%)	0	2/89 (2.2%)	2
CONFUS	0/88 (0%)	0	1/89 (1.1%)	1
FEVER	6/88 (6.8%)	7	5/89 (5.6%)	7
PAIN	0/88 (0%)	0	1/89 (1.1%)	2
Hepatobiliary disorders
LIVER FAIL	0/88 (0%)	0	1/89 (1.1%)	1
Immune system disorders
ALLERG REACT	1/88 (1.1%)	1	0/89 (0%)	0
IMMUNOGLOBUL DEC	1/88 (1.1%)	1	0/89 (0%)	0
Infections and infestations
CELLULITIS	1/88 (1.1%)	1	0/89 (0%)	0
INFECT	1/88 (1.1%)	1	2/89 (2.2%)	2
SEPSIS	2/88 (2.3%)	2	2/89 (2.2%)	2
Metabolism and nutrition disorders
ACIDOSIS	0/88 (0%)	0	1/89 (1.1%)	1
Musculoskeletal and connective tissue disorders
MYASTHENIA	0/88 (0%)	0	1/89 (1.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOR LYSIS SYNDROME	1/88 (1.1%)	1	0/89 (0%)	0
Renal and urinary disorders
KIDNEY FAIL	0/88 (0%)	0	3/89 (3.4%)	3
Respiratory, thoracic and mediastinal disorders
COUGH INC	0/88 (0%)	0	1/89 (1.1%)	1
DYSPNEA	0/88 (0%)	0	4/89 (4.5%)	4
EDEMA LUNG	1/88 (1.1%)	1	0/89 (0%)	0
EFFUS PLEURAL	0/88 (0%)	0	1/89 (1.1%)	1
LUNG DIS	1/88 (1.1%)	2	0/89 (0%)	0
PNEUMONIA	2/88 (2.3%)	2	2/89 (2.2%)	2
RESPIRAT DIS	0/88 (0%)	0	1/89 (1.1%)	1
SINUSITIS	1/88 (1.1%)	1	0/89 (0%)	0
Skin and subcutaneous tissue disorders
HYPOXIA	1/88 (1.1%)	1	1/89 (1.1%)	1
Other (Not Including Serious) Adverse Events
	FCR Arm		PCR Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	86/88 (97.7%)		87/89 (97.8%)
Blood and lymphatic system disorders
ANEMIA	45/88 (51.1%)	126	34/89 (38.2%)	82
EDEMA	3/88 (3.4%)	3	8/89 (9%)	14
EDEMA PERIPH	6/88 (6.8%)	6	5/89 (5.6%)	5
LEUKOPENIA	41/88 (46.6%)	267	34/89 (38.2%)	135
NEUTROPENIA	72/88 (81.8%)	271	68/89 (76.4%)	185
THROMBOCYTOPENIA	33/88 (37.5%)	87	24/89 (27%)	44
Gastrointestinal disorders
ANOREXIA	14/88 (15.9%)	20	23/89 (25.8%)	31
CONSTIP	16/88 (18.2%)	21	9/89 (10.1%)	16
DEHYDRAT	2/88 (2.3%)	2	5/89 (5.6%)	6
DIARRHEA	13/88 (14.8%)	18	12/89 (13.5%)	16
DYSPEPSIA	9/88 (10.2%)	16	3/89 (3.4%)	3
NAUSEA	47/88 (53.4%)	81	49/89 (55.1%)	123
PAIN ABDO	6/88 (6.8%)	7	5/89 (5.6%)	9
STOMATITIS	7/88 (8%)	11	4/89 (4.5%)	4
TASTE PERVERS	7/88 (8%)	9	10/89 (11.2%)	11
VOMIT	14/88 (15.9%)	18	25/89 (28.1%)	44
General disorders
ASTHENIA	48/88 (54.5%)	99	53/89 (59.6%)	97
CHILLS	18/88 (20.5%)	21	16/89 (18%)	25
FEVER	18/88 (20.5%)	24	30/89 (33.7%)	45
HEADACHE	10/88 (11.4%)	15	4/89 (4.5%)	5
INSOMNIA	8/88 (9.1%)	10	3/89 (3.4%)	4
PAIN	6/88 (6.8%)	7	9/89 (10.1%)	11
Immune system disorders
ALLERG REACT	2/88 (2.3%)	2	6/89 (6.7%)	7
Infections and infestations
INFECT	5/88 (5.7%)	8	5/89 (5.6%)	7
Metabolism and nutrition disorders
BILIRUBINEM	6/88 (6.8%)	7	2/89 (2.2%)	2
CREATININE INC	3/88 (3.4%)	3	7/89 (7.9%)	10
HYPERGLYCEM	6/88 (6.8%)	8	6/89 (6.7%)	7
LDH INC	5/88 (5.7%)	5	5/89 (5.6%)	7
SGOT INC	6/88 (6.8%)	6	3/89 (3.4%)	3
SGPT INC	9/88 (10.2%)	9	2/89 (2.2%)	2
Musculoskeletal and connective tissue disorders
ARTHRALGIA	3/88 (3.4%)	3	7/89 (7.9%)	8
Nervous system disorders
ANXIETY	2/88 (2.3%)	2	5/89 (5.6%)	5
DIZZINESS	7/88 (8%)	8	7/89 (7.9%)	8
NEUROPATHY	3/88 (3.4%)	3	6/89 (6.7%)	10
Renal and urinary disorders
URIN FREQUENCY	6/88 (6.8%)	6	2/89 (2.2%)	2
Respiratory, thoracic and mediastinal disorders
COUGH INC	8/88 (9.1%)	9	10/89 (11.2%)	11
DYSPNEA	9/88 (10.2%)	9	7/89 (7.9%)	9
Skin and subcutaneous tissue disorders
ALOPECIA	4/88 (4.5%)	4	6/89 (6.7%)	6
RASH	11/88 (12.5%)	16	12/89 (13.5%)	20
SKIN DRY	5/88 (5.7%)	6	6/89 (6.7%)	6

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.