A Study of Clofarabine for Older Patients With Newly Diagnosed Acute Myelogenous Leukemia (AML) (CLASSIC II)

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00373529
• Collaborator: (none)
• Enrollment: 116
• Locations: 20
• Arm: 1
• Duration (Months): 43
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Clolar (clofarabine injection) is approved by the Food and Drug Administration (FDA) for the treatment of pediatric patients 1 to 21 years old with relapsed acute lymphoblastic leukemia (ALL) who have had at least 2 prior treatment regimens.

This study will evaluate the efficacy of clofarabine in elderly patients with acute myelogenous leukemia (AML) who are unlikely to benefit from treatment with intensive chemotherapy regimens (cytarabine and anthracycline based regimens) used in younger patients with AML.

Condition or Disease	Intervention/Treatment	Phase
Acute Myelogenous Leukemia; Acute Myeloid Leukemia	Drug: clofarabine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 116 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Single Agent Clofarabine in Previously Untreated Older Adult Patients With Acute Myelogenous Leukemia (AML) for Whom Standard Induction Chemotherapy is Unlikely to be of Benefit
• Study Start Date: Oct 1, 2006
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Clofarabine Participants received an induction cycle of clofarabine 30 mg/m^2/day intravenous infusion for 5 consecutive days. Participants could then receive up to 5 additional cycles, repeated minimally every 28 days, of clofarabine 20 mg/m^2/day intravenous infusion for 5 consecutive days.	Drug: clofarabine; Induction cycle 1: cycle 1 of clofarabine 30 mg/m^2/day as a 1-hour intravenous infusion for 5 consecutive days. Reinduction (cycle 2) and/or Consolidation cycles (cycles 2-6): cycles repeated minimally every 28 days, of clofarabine 20 mg/m^2/day as a 1-hour intravenous infusion for 5 consecutive days.; Other Names: clolar

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving Overall Remission (OR) After No More Than Two Cycles (Approximately Month 2) [approximately Month 2]

   Best response was assessed by the Independent Response Review Panel(IRRP) after two cycles of treatment. Overall remission(OR) is the sum of complete remission(CR) and complete remission in the absence of platelet recovery(CRp). CR includes normal values for peripheral blood cell counts (absolute neutrophil and platelet) and leukemic blast cells from bone marrow biopsy or aspirate, and absence of extramedullary disease. Partial remission(PR) includes recovery of peripheral blood cells with improved but still abnormal values in leukemic blast cells.

Secondary Outcome Measures

1. Kaplan Meier Estimate for Duration of Remission (DOR) [Up to 2 years]

   DOR was defined as the number of days from achievement of OR as assessed by the Independent Response Review Panel (IRRP) until IRRP-determined disease recurrence or death (any cause), plus 1 day. Participants who initiated alternative antileukemic treatment while in remission were censored on the date the therapy was initiated or on the date of last follow-up.

2. Kaplan Meier Estimate for Disease-free Survival (DFS) [Up to 2 years]

   DFS was defined as the number of days from achievement of IRRP-determined overall response until IRRP-determined disease recurrence or death (any cause), regardless of intervening alternative antileukemic treatment, plus 1 day.

3. Kaplan Meier Estimates for Overall Survival (OS) [Up to 2 years]

   OS was defined as the number of days from first dose of clofarabine until death for all participants, plus 1 day.

4. Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment and Follow-up Periods [Up to 2 years]

   Participants with AEs that occurred during the treatment and follow-up periods. AEs were classified according to severity (graded using National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 3.0) and relationship to study drug. Treatment emergent is defined as any event that either first presents after baseline or worsens in severity after baseline. NCI Common Terminology Criteria for Severity: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5= Death related to AE

5. Percentage of Participants Who Died Within Thirty Days of Treatment (30-day Mortality Rate) [up to Day 30]

   Percentage of participants who died within 30 days of the first dose of study drug, regardless of cause.

Other Outcome Measures

1. Number of Participants Achieving Overall Remission After A Maximum of Two Cycles by Subgroup of Baseline Prognostic Factors [approximately Month 2]

   The number of participants within each subgroup of baseline prognostic factors of the full analysis set who achieved a best response of either a complete response (CR) or a complete response in the absence of platelet recovery (CRp) as determined by the Independent Response Review Panel following a maximum of two cycles of treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of AML (de novo, secondary or with an antecedent hematologic disorder [AHD])

• Age ≥ 60 years

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Presence of at least one adverse prognostic factor: Age ≥ 70 years; or AHD; or ECOG performance status of 2; or Intermediate or unfavorable (i.e., adverse) karyotype defined as any cytogenetic profile except the presence of any of the following:

• t(8;21)(q22;q22)

• inv(16)(p13;q22 or t(16;16)(p13;q22)

• t(15;17)(q22;q12) and variants.

• Adequate renal and hepatic function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN; and Serum creatinine ≤ 1.0 mg/dL; if serum creatinine > 1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be > 60 mL/min/1.73 m^2 as calculated by the Modification of Diet in Renal Disease (MDRD) equation

• Adequate cardiac function: left ventricular ejection fraction (LVEF) ≥ 40% or left ventricular fractional shortening ≥ 22%

Exclusion Criteria:

• Diagnosis of acute promyelocytic leukemia

• Prior treatment with clofarabine

• Prior treatment for AML or an antecedent hematologic disorder

• Prior hematopoietic stem cell transplant (HSCT)

• Prior radiation therapy to the pelvis

• Investigational agent received within 30 days prior to the first dose of study drug

• Ongoing uncontrolled systemic infection

• Diagnosis of another malignancy, unless the patient has been disease-free for at least 5 years following the completion of curative intent therapy with the following exceptions: Patients with treated non-melanoma skin cancer, in-situ carcinoma or cervical intraepithelial neoplasia regardless of disease-free duration are eligible for this study if definitive treatment for the condition has been completed; Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on PSA value are eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed

• Clinical evidence of central nervous system (CNS) involvement

• Severe concurrent medical condition or psychiatric disorder that would preclude study participation

• Positive human immunodeficiency virus (HIV) test

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinical Hospital	Phoenix	Arizona	United States
2	Arizona Cancer Center	Tucson	Arizona	United States
3	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States
4	Scripps Cancer Center	San Diego	California	United States
5	Rocky Mountain Cancer Centers	Denver	Colorado	United States
6	Cancer Center of Central Connecticut	Southington	Connecticut	United States
7	Emory University School of Medicine	Atlanta	Georgia	United States
8	Medical College of Georgia	Augusta	Georgia	United States
9	Rush University Medical Center	Chicago	Illinois	United States
10	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States
11	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States
12	Mount Sinai School of Medicine	New York	New York	United States
13	Oregon Health and Science University	Portland	Oregon	United States
14	Penn State Hershey Medical Center	Hershey	Pennsylvania	United States
15	Vanderbilt University Medical Center	Nashville	Tennessee	United States
16	University of MD Anderson Cancer Center	Houston	Texas	United States
17	Cancer Care Centers of South Texas	San Antonio	Texas	United States
18	University of Utah - Huntsman Cancer Institute	Salt Lake City	Utah	United States
19	Seattle Cancer Care Alliance	Seattle	Washington	United States
20	West Virginia University - HSC	Morgantown	West Virginia	United States

Sponsors and Collaborators

• Genzyme, a Sanofi Company

Investigators

• Study Director: Medical Monitor, Genzyme, a Sanofi Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT00373529
• Other Study ID Numbers: CLO24300606
• First Posted: Sep 8, 2006
• Last Update Posted: Apr 14, 2014
• Last Verified: Mar 1, 2014

• Keywords provided by Genzyme, a Sanofi Company: Acute myelogenous leukemia; Acute myeloid leukemia; newly Diagnosed AML; Clofarabine; CLASSIC II; CLO243
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Clofarabine

Study Results

Participant Flow

Pre-assignment Detail	129 patients were screened and 116 participants enrolled/treated at 20 sites.

Arm/Group Title	Clofarabine
Arm/Group Description	Participants received an induction cycle of clofarabine 30 mg/m^2/day intravenous infusion for 5 consecutive days. Participants could then receive up to 5 additional cycles, repeated minimally every 28 days, of clofarabine 20 mg/m^2/day intravenous infusion for 5 consecutive days.
Period Title: Overall Study
STARTED	116
Full Analysis Set	112
COMPLETED	8
NOT COMPLETED	108

Baseline Characteristics

Arm/Group Title	Clofarabine
Arm/Group Description	Participants received an induction cycle of clofarabine 30 mg/m^2/day intravenous infusion for 5 consecutive days. Participants could then receive up to 5 additional cycles, repeated minimally every 28 days, of clofarabine 20 mg/m^2/day intravenous infusion for 5 consecutive days.
Overall Participants	112
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.4 (5.92)
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	71.0
Sex: Female, Male (Count of Participants)
Female	60 53.6%
Male	52 46.4%
Race (participants) [Number]
American Indian or Alaska Native	1 0.9%
Asian	4 3.6%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	7 6.3%
White	98 87.5%
Other	2 1.8%
Ethnicity (participants) [Number]
Hispanic or Latino	4 3.6%
Not Hispanic or Latino	108 96.4%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	166.50 (10.366)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	78.45 (18.191)
Age at Enrollment (participants) [Number]
>= 70 years	69 61.6%
< 70 years	43 38.4%
Antecedent Hematologic Disorder (participants) [Number]
Yes	41 36.6%
No	67 59.8%
Not reported	4 3.6%
Eastern Cooperative Oncology Group Performance Status (participants) [Number]
ECOG 5	0 0%
ECOG 4	0 0%
ECOG 3	0 0%
ECOG 2	25 22.3%
ECOG 1	66 58.9%
ECOG 0	21 18.8%
Karyotype (participants) [Number]
Intermediate	46 41.1%
Unfavorable	62 55.4%
Favorable	0 0%
Not reported	4 3.6%
Participants Summarized by Number of Adverse Prognostic Factors (participants) [Number]
0 Adverse Prognostic Factors	0 0%
1 Adverse Prognostic Factor	25 22.3%
2 Adverse Prognostic Factors	45 40.2%
3 Adverse Prognostic Factors	40 35.7%
4 Adverse Prognostic Factors	2 1.8%
Participants Summarized by Number of Adverse Prognostic Factors Excluding Intermediate Karyotype (participants) [Number]
0 Adverse Prognostic Factors	7 6.3%
1 Adverse Prognostic Factor	42 37.5%
2 Adverse Prognostic Factors	35 31.3%
3 Adverse Prognostic Factors	27 24.1%
4 Adverse Prognostic Factors	1 0.9%
Secondary acute myeloid leukemia (AML) at baseline (participants) [Number]
Yes	11 9.8%
No	101 90.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving Overall Remission (OR) After No More Than Two Cycles (Approximately Month 2)
Description	Best response was assessed by the Independent Response Review Panel(IRRP) after two cycles of treatment. Overall remission(OR) is the sum of complete remission(CR) and complete remission in the absence of platelet recovery(CRp). CR includes normal values for peripheral blood cell counts (absolute neutrophil and platelet) and leukemic blast cells from bone marrow biopsy or aspirate, and absence of extramedullary disease. Partial remission(PR) includes recovery of peripheral blood cells with improved but still abnormal values in leukemic blast cells.
Time Frame	approximately Month 2

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS)

Arm/Group Title	Clofarabine
Arm/Group Description	Participants received an induction cycle of clofarabine 30 mg/m^2/day intravenous infusion for 5 consecutive days. Participants could then receive up to 5 additional cycles, repeated minimally every 28 days, of clofarabine 20 mg/m^2/day intravenous infusion for 5 consecutive days.
Measure Participants	112
Overall Remission (OR=CR+CRp)	45.5 40.6%
Complete Remission (CR)	37.5 33.5%
Complete Remission w/o platelet recovery (CRp)	8.0 7.1%
Partial Remission (PR)	3.6 3.2%
Treatment Failure (TF)	50.9 45.4%

2. Secondary Outcome

Title	Kaplan Meier Estimate for Duration of Remission (DOR)
Description	DOR was defined as the number of days from achievement of OR as assessed by the Independent Response Review Panel (IRRP) until IRRP-determined disease recurrence or death (any cause), plus 1 day. Participants who initiated alternative antileukemic treatment while in remission were censored on the date the therapy was initiated or on the date of last follow-up.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) of participants who achieved remission.

Arm/Group Title	Clofarabine
Arm/Group Description	Participants received an induction cycle of clofarabine 30 mg/m^2/day intravenous infusion for 5 consecutive days. Participants could then receive up to 5 additional cycles, repeated minimally every 28 days, of clofarabine 20 mg/m^2/day intravenous infusion for 5 consecutive days.
Measure Participants	51
Median (95% Confidence Interval) [weeks]	55.6

3. Secondary Outcome

Title	Kaplan Meier Estimate for Disease-free Survival (DFS)
Description	DFS was defined as the number of days from achievement of IRRP-determined overall response until IRRP-determined disease recurrence or death (any cause), regardless of intervening alternative antileukemic treatment, plus 1 day.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) of participants who achieved remission.

Arm/Group Title	Clofarabine
Arm/Group Description	Participants received an induction cycle of clofarabine 30 mg/m^2/day intravenous infusion for 5 consecutive days. Participants could then receive up to 5 additional cycles, repeated minimally every 28 days, of clofarabine 20 mg/m^2/day intravenous infusion for 5 consecutive days.
Measure Participants	51
Median (95% Confidence Interval) [weeks]	43.8

4. Secondary Outcome

Title	Kaplan Meier Estimates for Overall Survival (OS)
Description	OS was defined as the number of days from first dose of clofarabine until death for all participants, plus 1 day.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Clofarabine
Arm/Group Description	Participants received an induction cycle of clofarabine 30 mg/m^2/day intravenous infusion for 5 consecutive days. Participants could then receive up to 5 additional cycles, repeated minimally every 28 days, of clofarabine 20 mg/m^2/day intravenous infusion for 5 consecutive days.
Measure Participants	112
Median (95% Confidence Interval) [weeks]	40.7

5. Secondary Outcome

Title	Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment and Follow-up Periods
Description	Participants with AEs that occurred during the treatment and follow-up periods. AEs were classified according to severity (graded using National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 3.0) and relationship to study drug. Treatment emergent is defined as any event that either first presents after baseline or worsens in severity after baseline. NCI Common Terminology Criteria for Severity: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5= Death related to AE
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Clofarabine
Arm/Group Description	Participants received an induction cycle of clofarabine 30 mg/m^2/day intravenous infusion for 5 consecutive days. Participants could then receive up to 5 additional cycles, repeated minimally every 28 days, of clofarabine 20 mg/m^2/day intravenous infusion for 5 consecutive days.
Measure Participants	112
Treatment-emergent AEs (TEAE)	112 100%
Treatment-emergent AEs related to study drug	108 96.4%
Treatment-emergent serious AEs	76 67.9%
Treatment-emergent serious AEs related to drug	41 36.6%
Discontinued due to AEs	7 6.3%
Died w/i treatment period-w/i 45 days of last dose	22 19.6%
Died due to drug-related AEs	4 3.6%
Died within 30 days of first dose	11 9.8%
Died w/i 30 days of first dose due to related AEs	3 2.7%
Grade 1: maximum severity rating for any TEAE	2 1.8%
Grade 2: maximum severity rating for any TEAE	6 5.4%
Grade 3: maximum severity rating for any TEAE	46 41.1%
Grade 4: maximum severity rating for any TEAE	34 30.4%
Grade 5: maximum severity rating for any TEAE	24 21.4%

6. Secondary Outcome

Title	Percentage of Participants Who Died Within Thirty Days of Treatment (30-day Mortality Rate)
Description	Percentage of participants who died within 30 days of the first dose of study drug, regardless of cause.
Time Frame	up to Day 30

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Clofarabine
Arm/Group Description	Participants received an induction cycle of clofarabine 30 mg/m^2/day intravenous infusion for 5 consecutive days. Participants could then receive up to 5 additional cycles, repeated minimally every 28 days, of clofarabine 20 mg/m^2/day intravenous infusion for 5 consecutive days.
Measure Participants	112
Number [percentage of participants]	9.8 8.8%

7. Other Pre-specified Outcome

Title	Number of Participants Achieving Overall Remission After A Maximum of Two Cycles by Subgroup of Baseline Prognostic Factors
Description	The number of participants within each subgroup of baseline prognostic factors of the full analysis set who achieved a best response of either a complete response (CR) or a complete response in the absence of platelet recovery (CRp) as determined by the Independent Response Review Panel following a maximum of two cycles of treatment.
Time Frame	approximately Month 2

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) of participants who achieved remission and had baseline prognostic factor

Arm/Group Title	Clofarabine
Arm/Group Description	Participants received an induction cycle of clofarabine 30 mg/m^2/day intravenous infusion for 5 consecutive days. Participants could then receive up to 5 additional cycles, repeated minimally every 28 days, of clofarabine 20 mg/m^2/day intravenous infusion for 5 consecutive days.
Measure Participants	112
Age >=70 (n=69)	27 24.1%
Age <70 (n=43)	24 21.4%
Antecedent hematologic disorder - Yes (n=41)	21 18.8%
Antecedent hematologic disorder - No (n=67)	29 25.9%
Antecedent hematologic disorder-Not reported (n=4)	1 0.9%
ECOG Performance Status = 0-1 (n=87)	43 38.4%
ECOG Performance Status = 2 (n=25)	8 7.1%
Karyotype = Intermediate (n=46)	25 22.3%
Karyotype = Unfavorable (n=62)	26 23.2%
Karyotype = Not Reported (n=4)	0 0%

Adverse Events

Time Frame	Up to 2 years.
Adverse Event Reporting Description	In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables.
Arm/Group Title	Clofarabine
Arm/Group Description	Participants received an induction cycle of clofarabine 30 mg/m^2/day intravenous infusion for 5 consecutive days. Participants could then receive up to 5 additional cycles, repeated minimally every 28 days, of clofarabine 20 mg/m^2/day intravenous infusion for 5 consecutive days.
All Cause Mortality
	Clofarabine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Clofarabine
	Affected / at Risk (%)	# Events
Total	76/112 (67.9%)
Blood and lymphatic system disorders
Anaemia	1/112 (0.9%)
Bone marrow failure	1/112 (0.9%)
Disseminated intravascular coagulation	2/112 (1.8%)
Febrile neutropenia	28/112 (25%)
Neutropenia	2/112 (1.8%)
Thrombocytopenia	2/112 (1.8%)
Cardiac disorders
Acute myocardial infarction	1/112 (0.9%)
Atrial fibrillation	7/112 (6.3%)
Cardiac failure congestive	3/112 (2.7%)
Cardio-respiratory arrest	1/112 (0.9%)
Cardiomyopathy	1/112 (0.9%)
Myocardial infarction	1/112 (0.9%)
Sinus tachycardia	1/112 (0.9%)
Tachycardia	1/112 (0.9%)
Gastrointestinal disorders
Abdominal pain	1/112 (0.9%)
Diarrhoea	3/112 (2.7%)
Gastrointestinal haemorrhage	4/112 (3.6%)
Haematemesis	1/112 (0.9%)
Haematochezia	1/112 (0.9%)
Ileus	1/112 (0.9%)
Melaena	1/112 (0.9%)
Mouth haemorrhage	1/112 (0.9%)
Nausea	1/112 (0.9%)
Pancreatitis	1/112 (0.9%)
Upper gastrointestinal haemorrhage	1/112 (0.9%)
Vomiting	2/112 (1.8%)
General disorders
Asthenia	2/112 (1.8%)
Fatigue	2/112 (1.8%)
Multi-organ failure	2/112 (1.8%)
Organ failure	1/112 (0.9%)
Pyrexia	1/112 (0.9%)
Infections and infestations
Abscess intestinal	1/112 (0.9%)
Bacteraemia	4/112 (3.6%)
Bacterial infection	1/112 (0.9%)
Bacterial sepsis	1/112 (0.9%)
Bronchopulmonary aspergillosis	4/112 (3.6%)
Candidiasis	1/112 (0.9%)
Cellulitis	4/112 (3.6%)
Clostridial infection	2/112 (1.8%)
Clostridium difficile colitis	1/112 (0.9%)
Device related infection	6/112 (5.4%)
Device related sepsis	1/112 (0.9%)
Diverticulitis	2/112 (1.8%)
Enterococcal bacteraemia	3/112 (2.7%)
Enterococcal sepsis	2/112 (1.8%)
Escherichia bacteraemia	1/112 (0.9%)
Herpes oesophagitis	1/112 (0.9%)
Influenza	1/112 (0.9%)
Lobar pneumonia	1/112 (0.9%)
Oesophageal candidiasis	2/112 (1.8%)
Oral bacterial infection	1/112 (0.9%)
Oral candidiasis	1/112 (0.9%)
Pneumocystis jiroveci pneumonia	1/112 (0.9%)
Pneumonia	16/112 (14.3%)
Pneumonia bacterial	1/112 (0.9%)
Pneumonia chlamydial	1/112 (0.9%)
Pneumonia cytomegaloviral	1/112 (0.9%)
Pneumonia fungal	3/112 (2.7%)
Pseudomonal sepsis	1/112 (0.9%)
Pseudomonas infection	1/112 (0.9%)
Respiratory moniliasis	1/112 (0.9%)
Sepsis	6/112 (5.4%)
Septic shock	2/112 (1.8%)
Sinusitis	1/112 (0.9%)
Sinusitis bacterial	1/112 (0.9%)
Sinusitis fungal	1/112 (0.9%)
Staphylococcal bacteraemia	3/112 (2.7%)
Staphylococcal infection	3/112 (2.7%)
Staphylococcal sepsis	1/112 (0.9%)
Urinary tract infection	4/112 (3.6%)
Urinary tract infection bacterial	1/112 (0.9%)
Urinary tract infection enterococcal	1/112 (0.9%)
Investigations
Alanine aminotransferase increased	1/112 (0.9%)
Aspartate aminotransferase increased	1/112 (0.9%)
Bacterial test	1/112 (0.9%)
Bacterial test positive	2/112 (1.8%)
Blood creatine phosphokinase increased	1/112 (0.9%)
Staphylococcus test positive	1/112 (0.9%)
Troponin I increased	1/112 (0.9%)
Metabolism and nutrition disorders
Dehydration	5/112 (4.5%)
Fluid overload	2/112 (1.8%)
Hypocalcaemia	1/112 (0.9%)
Hypokalaemia	2/112 (1.8%)
Hypomagnesaemia	1/112 (0.9%)
Musculoskeletal and connective tissue disorders
Bone pain	1/112 (0.9%)
Muscular weakness	2/112 (1.8%)
Musculoskeletal pain	1/112 (0.9%)
Neck pain	1/112 (0.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	3/112 (2.7%)
Malignant neoplasm progression	3/112 (2.7%)
Nervous system disorders
Cerebrovascular accident	1/112 (0.9%)
Grand mal convulsion	1/112 (0.9%)
Haemorrhage intracranial	1/112 (0.9%)
Somnolence	2/112 (1.8%)
Status epilepticus	1/112 (0.9%)
Syncope	3/112 (2.7%)
Transient ischaemic attack	1/112 (0.9%)
Psychiatric disorders
Agitation	1/112 (0.9%)
Confusional state	1/112 (0.9%)
Delirium	1/112 (0.9%)
Hallucination	2/112 (1.8%)
Renal and urinary disorders
Haematuria	2/112 (1.8%)
Renal failure	2/112 (1.8%)
Renal failure acute	9/112 (8%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	2/112 (1.8%)
Chronic obstructive pulmonary disease	1/112 (0.9%)
Dyspnoea	3/112 (2.7%)
Pulmonary alveolar haemorrhage	1/112 (0.9%)
Pulmonary haemorrhage	1/112 (0.9%)
Pulmonary oedema	3/112 (2.7%)
Respiratory distress	3/112 (2.7%)
Respiratory failure	4/112 (3.6%)
Skin and subcutaneous tissue disorders
Rash	1/112 (0.9%)
Vascular disorders
Hypotension	2/112 (1.8%)
Jugular vein thrombosis	1/112 (0.9%)
Orthostatic hypotension	1/112 (0.9%)
Peripheral arterial occlusive disease	1/112 (0.9%)
Other (Not Including Serious) Adverse Events
	Clofarabine
	Affected / at Risk (%)	# Events
Total	112/112 (100%)
Blood and lymphatic system disorders
Anaemia	12/112 (10.7%)
Coagulopathy	2/112 (1.8%)
Disseminated intravascular coagulation	4/112 (3.6%)
Eosinophilia	1/112 (0.9%)
Febrile neutropenia	50/112 (44.6%)
Hypergammaglobulinaemia	1/112 (0.9%)
Hypocoagulable state	1/112 (0.9%)
Hypoprothrombinaemia	1/112 (0.9%)
Leukopenia	2/112 (1.8%)
Lymph node calcification	1/112 (0.9%)
Lymphadenopathy	5/112 (4.5%)
Lymphocytic infiltration	1/112 (0.9%)
Neutropenia	21/112 (18.8%)
Pancytopenia	4/112 (3.6%)
Platelet disorder	1/112 (0.9%)
Splenic granuloma	1/112 (0.9%)
Splenomegaly	2/112 (1.8%)
Thrombocytopenia	18/112 (16.1%)
White blood cell disorder	1/112 (0.9%)
Cardiac disorders
Acute myocardial infarction	1/112 (0.9%)
Angina pectoris	4/112 (3.6%)
Aortic valve disease	1/112 (0.9%)
Aortic valve incompetence	1/112 (0.9%)
Arrhythmia	1/112 (0.9%)
Arteriosclerosis coronary artery	4/112 (3.6%)
Atrial fibrillation	11/112 (9.8%)
Bradycardia	4/112 (3.6%)
Cardiac failure chronic	1/112 (0.9%)
Cardiac failure congestive	3/112 (2.7%)
Cardiomegaly	8/112 (7.1%)
Cardiomyopathy	3/112 (2.7%)
Coronary artery disease	1/112 (0.9%)
Diastolic dysfunction	2/112 (1.8%)
Dilatation atrial	1/112 (0.9%)
Dilatation ventricular	2/112 (1.8%)
Electromechanical dissociation	1/112 (0.9%)
Extrasystoles	2/112 (1.8%)
Heart valve incompetence	1/112 (0.9%)
Left atrial dilatation	5/112 (4.5%)
Left ventricular hypertrophy	4/112 (3.6%)
Mitral valve calcification	1/112 (0.9%)
Mitral valve incompetence	3/112 (2.7%)
Palpitations	6/112 (5.4%)
Pericardial cyst	1/112 (0.9%)
Pericardial effusion	11/112 (9.8%)
Pulmonary valve incompetence	2/112 (1.8%)
Right atrial dilatation	1/112 (0.9%)
Right ventricular dysfunction	1/112 (0.9%)
Sinus bradycardia	3/112 (2.7%)
Sinus tachycardia	7/112 (6.3%)
Supraventricular extrasystoles	2/112 (1.8%)
Supraventricular tachycardia	1/112 (0.9%)
Tachycardia	25/112 (22.3%)
Tricuspid valve incompetence	3/112 (2.7%)
Ventricular extrasystoles	3/112 (2.7%)
Ventricular hypokinesia	1/112 (0.9%)
Ear and labyrinth disorders
Cerumen impaction	1/112 (0.9%)
Ear congestion	2/112 (1.8%)
Ear discomfort	2/112 (1.8%)
Ear pain	2/112 (1.8%)
Hypoacusis	2/112 (1.8%)
Tinnitus	1/112 (0.9%)
Tympanic membrane disorder	1/112 (0.9%)
Vertigo	5/112 (4.5%)
Endocrine disorders
Adrenal insufficiency	1/112 (0.9%)
Inappropriate antidiuretic hormone secre	1/112 (0.9%)
Eye disorders
Conjunctival haemorrhage	3/112 (2.7%)
Conjunctival hyperaemia	1/112 (0.9%)
Conjunctival oedema	1/112 (0.9%)
Conjunctivitis	3/112 (2.7%)
Diplopia	2/112 (1.8%)
Dry eye	8/112 (7.1%)
Eye disorder	1/112 (0.9%)
Eye oedema	1/112 (0.9%)
Eye swelling	1/112 (0.9%)
Eyelid disorder	1/112 (0.9%)
Eyelid oedema	1/112 (0.9%)
Eyelid ptosis	1/112 (0.9%)
Lacrimation increased	2/112 (1.8%)
Mydriasis	1/112 (0.9%)
Ocular hyperaemia	1/112 (0.9%)
Photophobia	2/112 (1.8%)
Pinguecula	1/112 (0.9%)
Scleral oedema	1/112 (0.9%)
Vision blurred	6/112 (5.4%)
Visual acuity reduced	1/112 (0.9%)
Visual impairment	4/112 (3.6%)
Vitreous haemorrhage	1/112 (0.9%)
Gastrointestinal disorders
Abdominal discomfort	6/112 (5.4%)
Abdominal distension	14/112 (12.5%)
Abdominal pain	27/112 (24.1%)
Abdominal pain lower	4/112 (3.6%)
Abdominal pain upper	6/112 (5.4%)
Abdominal tenderness	8/112 (7.1%)
Anal fissure	1/112 (0.9%)
Anal pruritus	1/112 (0.9%)
Anorectal discomfort	1/112 (0.9%)
Aphthous stomatitis	1/112 (0.9%)
Ascites	1/112 (0.9%)
Bowel movement irregularity	1/112 (0.9%)
Caecitis	1/112 (0.9%)
Chapped lips	1/112 (0.9%)
Cheilitis	1/112 (0.9%)
Constipation	48/112 (42.9%)
Dental caries	1/112 (0.9%)
Diarrhoea	72/112 (64.3%)
Diverticulum	2/112 (1.8%)
Dry mouth	13/112 (11.6%)
Dyspepsia	16/112 (14.3%)
Dysphagia	10/112 (8.9%)
Epigastric discomfort	1/112 (0.9%)
Faecal incontinence	5/112 (4.5%)
Faecaloma	1/112 (0.9%)
Faeces hard	1/112 (0.9%)
Flatulence	8/112 (7.1%)
Gastrointestinal haemorrhage	2/112 (1.8%)
Gastrointestinal sounds abnormal	1/112 (0.9%)
Gastrooesophageal reflux disease	5/112 (4.5%)
Gingival bleeding	2/112 (1.8%)
Gingival pain	1/112 (0.9%)
Gingivitis	4/112 (3.6%)
Glossodynia	1/112 (0.9%)
Haematemesis	2/112 (1.8%)
Haematochezia	4/112 (3.6%)
Haemorrhoidal haemorrhage	4/112 (3.6%)
Haemorrhoids	15/112 (13.4%)
Hiatus hernia	5/112 (4.5%)
Hypoaesthesia oral	1/112 (0.9%)
Ileus	4/112 (3.6%)
Lip blister	1/112 (0.9%)
Lip dry	6/112 (5.4%)
Lip swelling	1/112 (0.9%)
Lip ulceration	2/112 (1.8%)
Loose tooth	1/112 (0.9%)
Melaena	3/112 (2.7%)
Mouth haemorrhage	10/112 (8.9%)
Mouth ulceration	6/112 (5.4%)
Nausea	85/112 (75.9%)
Odynophagia	3/112 (2.7%)
Oesophagitis	1/112 (0.9%)
Oral discomfort	1/112 (0.9%)
Oral disorder	4/112 (3.6%)
Oral pain	5/112 (4.5%)
Pancreatic atrophy	1/112 (0.9%)
Pancreatitis	5/112 (4.5%)
Proctalgia	1/112 (0.9%)
Proctitis ulcerative	1/112 (0.9%)
Rectal haemorrhage	3/112 (2.7%)
Rectal prolapse	1/112 (0.9%)
Retching	2/112 (1.8%)
Saliva altered	1/112 (0.9%)
Stomatitis	12/112 (10.7%)
Tongue discolouration	1/112 (0.9%)
Tongue disorder	1/112 (0.9%)
Tongue haemorrhage	1/112 (0.9%)
Toothache	2/112 (1.8%)
Upper gastrointestinal haemorrhage	1/112 (0.9%)
Vomiting	63/112 (56.3%)
General disorders
Asthenia	22/112 (19.6%)
Catheter site discharge	4/112 (3.6%)
Catheter site erythema	21/112 (18.8%)
Catheter site haematoma	4/112 (3.6%)
Catheter site haemorrhage	5/112 (4.5%)
Catheter site inflammation	2/112 (1.8%)
Catheter site oedema	1/112 (0.9%)
Catheter site pain	13/112 (11.6%)
Catheter site rash	2/112 (1.8%)
Catheter site related reaction	2/112 (1.8%)
Chest discomfort	5/112 (4.5%)
Chest pain	5/112 (4.5%)
Chills	40/112 (35.7%)
Device occlusion	2/112 (1.8%)
Discomfort	1/112 (0.9%)
Face oedema	1/112 (0.9%)
Facial pain	2/112 (1.8%)
Fatigue	40/112 (35.7%)
Gait disturbance	1/112 (0.9%)
General physical health deterioration	1/112 (0.9%)
Generalised oedema	5/112 (4.5%)
Granuloma	1/112 (0.9%)
Hypothermia	1/112 (0.9%)
Infusion site induration	1/112 (0.9%)
Infusion site urticaria	1/112 (0.9%)
Injection site haematoma	1/112 (0.9%)
Irritability	2/112 (1.8%)
Local swelling	1/112 (0.9%)
Localised oedema	3/112 (2.7%)
Malaise	9/112 (8%)
Mucosal dryness	3/112 (2.7%)
Mucosal inflammation	18/112 (16.1%)
Non-cardiac chest pain	4/112 (3.6%)
Oedema	8/112 (7.1%)
Oedema peripheral	63/112 (56.3%)
Pain	12/112 (10.7%)
Pyrexia	44/112 (39.3%)
Swelling	1/112 (0.9%)
Temperature intolerance	1/112 (0.9%)
Thrombosis in device	3/112 (2.7%)
Hepatobiliary disorders
Cholelithiasis	4/112 (3.6%)
Gallbladder disorder	2/112 (1.8%)
Gallbladder oedema	2/112 (1.8%)
Granulomatous liver disease	1/112 (0.9%)
Hepatic cirrhosis	1/112 (0.9%)
Hepatic cyst	3/112 (2.7%)
Hepatic lesion	1/112 (0.9%)
Hyperbilirubinaemia	10/112 (8.9%)
Jaundice	2/112 (1.8%)
Portal hypertension	1/112 (0.9%)
Immune system disorders
Drug hypersensitivity	6/112 (5.4%)
Hypersensitivity	1/112 (0.9%)
Seasonal allergy	2/112 (1.8%)
Infections and infestations
Alpha haemolytic streptococcal infection	1/112 (0.9%)
Atypical mycobacterial infection	1/112 (0.9%)
Bacteraemia	4/112 (3.6%)
Bacterial infection	3/112 (2.7%)
Bacteroides infection	1/112 (0.9%)
Bronchopulmonary aspergillosis	1/112 (0.9%)
Candidiasis	4/112 (3.6%)
Cellulitis	6/112 (5.4%)
Chronic sinusitis	1/112 (0.9%)
Clostridial infection	4/112 (3.6%)
Clostridium difficile colitis	7/112 (6.3%)
Cystitis	1/112 (0.9%)
Device related infection	4/112 (3.6%)
Device related sepsis	1/112 (0.9%)
Enterobacter infection	1/112 (0.9%)
Enterococcal bacteraemia	3/112 (2.7%)
Enterococcal infection	5/112 (4.5%)
Escherichia bacteraemia	1/112 (0.9%)
Escherichia sepsis	1/112 (0.9%)
Folliculitis	1/112 (0.9%)
Fungal infection	2/112 (1.8%)
Gastroenteritis viral	1/112 (0.9%)
Gastrointestinal candidiasis	1/112 (0.9%)
Genital herpes	3/112 (2.7%)
Hepatitis b	1/112 (0.9%)
Herpes simplex	1/112 (0.9%)
Herpes zoster	1/112 (0.9%)
Jc virus infection	1/112 (0.9%)
Lobar pneumonia	1/112 (0.9%)
Lung infection pseudomonal	1/112 (0.9%)
Mastoiditis	1/112 (0.9%)
Morganella infection	1/112 (0.9%)
Nasopharyngitis	1/112 (0.9%)
Neutropenic infection	1/112 (0.9%)
Neutropenic sepsis	2/112 (1.8%)
Oral candidiasis	18/112 (16.1%)
Oral herpes	5/112 (4.5%)
Oral viral infection	1/112 (0.9%)
Otitis media	1/112 (0.9%)
Perineal abscess	1/112 (0.9%)
Pneumonia	17/112 (15.2%)
Pneumonia bacterial	1/112 (0.9%)
Pneumonia fungal	3/112 (2.7%)
Post procedural cellulitis	1/112 (0.9%)
Pseudomonal sepsis	1/112 (0.9%)
Pseudomonas infection	1/112 (0.9%)
Pulmonary mycosis	2/112 (1.8%)
Pyelonephritis	1/112 (0.9%)
Rash pustular	1/112 (0.9%)
Respiratory moniliasis	1/112 (0.9%)
Septic shock	1/112 (0.9%)
Sinusitis	2/112 (1.8%)
Sinusitis fungal	1/112 (0.9%)
Staphylococcal bacteraemia	8/112 (7.1%)
Staphylococcal infection	4/112 (3.6%)
Streptococcal bacteraemia	1/112 (0.9%)
Tinea pedis	1/112 (0.9%)
Upper respiratory tract infection	3/112 (2.7%)
Urinary tract infection	5/112 (4.5%)
Urinary tract infection bacterial	1/112 (0.9%)
Urinary tract infection enterococcal	1/112 (0.9%)
Urinary tract infection pseudomonal	1/112 (0.9%)
Vulval abscess	1/112 (0.9%)
Injury, poisoning and procedural complications
Allergic transfusion reaction	1/112 (0.9%)
Contusion	17/112 (15.2%)
Excoriation	3/112 (2.7%)
Fall	3/112 (2.7%)
Muscle strain	1/112 (0.9%)
Periorbital haematoma	3/112 (2.7%)
Pocket erosion	1/112 (0.9%)
Post procedural haemorrhage	2/112 (1.8%)
Post-traumatic pain	2/112 (1.8%)
Postoperative wound complication	1/112 (0.9%)
Procedural pain	7/112 (6.3%)
Renal haematoma	1/112 (0.9%)
Skeletal injury	1/112 (0.9%)
Skin laceration	5/112 (4.5%)
Spinal compression fracture	1/112 (0.9%)
Subdural haematoma	1/112 (0.9%)
Subdural haemorrhage	1/112 (0.9%)
Transfusion reaction	4/112 (3.6%)
Wound dehiscence	1/112 (0.9%)
Investigations
Alanine aminotransferase increased	26/112 (23.2%)
Antibiotic resistant staphylococcus test	1/112 (0.9%)
Aspartate aminotransferase increased	24/112 (21.4%)
Bacterial test positive	1/112 (0.9%)
Blood albumin decreased	1/112 (0.9%)
Blood alkaline phosphatase increased	5/112 (4.5%)
Blood amylase increased	5/112 (4.5%)
Blood bicarbonate decreased	1/112 (0.9%)
Blood bicarbonate increased	1/112 (0.9%)
Blood bilirubin increased	7/112 (6.3%)
Blood chloride decreased	1/112 (0.9%)
Blood creatinine increased	13/112 (11.6%)
Blood culture positive	2/112 (1.8%)
Blood glucose increased	1/112 (0.9%)
Blood lactate dehydrogenase increased	3/112 (2.7%)
Blood phosphorus decreased	2/112 (1.8%)
Blood phosphorus increased	2/112 (1.8%)
Blood potassium decreased	1/112 (0.9%)
Blood pressure increased	1/112 (0.9%)
Blood sodium decreased	1/112 (0.9%)
Blood urea increased	1/112 (0.9%)
Blood urine present	1/112 (0.9%)
Bone density increased	1/112 (0.9%)
Brain natriuretic peptide increased	3/112 (2.7%)
Breath sounds abnormal	10/112 (8.9%)
Cardiac murmur	10/112 (8.9%)
Chest x-ray abnormal	3/112 (2.7%)
Clostridium test positive	1/112 (0.9%)
Coagulation time prolonged	1/112 (0.9%)
Culture urine positive	2/112 (1.8%)
Electrocardiogram qt prolonged	3/112 (2.7%)
Electrocardiogram st segment abnormal	1/112 (0.9%)
Electrocardiogram st segment depression	1/112 (0.9%)
Electrocardiogram t wave abnormal	4/112 (3.6%)
Enterococcus test positive	3/112 (2.7%)
Eosinophil count increased	1/112 (0.9%)
Face and mouth x-ray abnormal	1/112 (0.9%)
Fungal test positive	1/112 (0.9%)
Haemoglobin	1/112 (0.9%)
Haemoglobin decreased	1/112 (0.9%)
Heart rate irregular	4/112 (3.6%)
Heart sounds abnormal	1/112 (0.9%)
International normalised ratio increased	1/112 (0.9%)
Lipase increased	7/112 (6.3%)
Liver function test abnormal	3/112 (2.7%)
Liver palpable subcostal	1/112 (0.9%)
Occult blood positive	3/112 (2.7%)
Oxygen saturation decreased	1/112 (0.9%)
Protein total decreased	1/112 (0.9%)
Pulmonary arterial pressure increased	1/112 (0.9%)
Right ventricular systolic pressure incr	1/112 (0.9%)
Streptococcus test positive	2/112 (1.8%)
Transaminases increased	8/112 (7.1%)
Troponin I	1/112 (0.9%)
Troponin I increased	1/112 (0.9%)
Urine analysis abnormal	1/112 (0.9%)
Urine output decreased	2/112 (1.8%)
Weight decreased	17/112 (15.2%)
Weight increased	3/112 (2.7%)
White blood cell count decreased	1/112 (0.9%)
Metabolism and nutrition disorders
Acidosis	1/112 (0.9%)
Cachexia	2/112 (1.8%)
Decreased appetite	45/112 (40.2%)
Dehydration	8/112 (7.1%)
Diabetes mellitus	1/112 (0.9%)
Fluid imbalance	1/112 (0.9%)
Fluid overload	18/112 (16.1%)
Fluid retention	2/112 (1.8%)
Gout	2/112 (1.8%)
Hypercalcaemia	1/112 (0.9%)
Hyperglycaemia	10/112 (8.9%)
Hyperkalaemia	2/112 (1.8%)
Hypermagnesaemia	1/112 (0.9%)
Hypernatraemia	1/112 (0.9%)
Hyperphosphataemia	7/112 (6.3%)
Hyperuricaemia	2/112 (1.8%)
Hypervolaemia	1/112 (0.9%)
Hypoalbuminaemia	6/112 (5.4%)
Hypocalcaemia	7/112 (6.3%)
Hypochloraemia	1/112 (0.9%)
Hypoglycaemia	1/112 (0.9%)
Hypokalaemia	36/112 (32.1%)
Hypomagnesaemia	14/112 (12.5%)
Hyponatraemia	9/112 (8%)
Hypophagia	1/112 (0.9%)
Hypophosphataemia	13/112 (11.6%)
Increased appetite	1/112 (0.9%)
Metabolic acidosis	1/112 (0.9%)
Metabolic alkalosis	1/112 (0.9%)
Podagra	1/112 (0.9%)
Polydipsia	1/112 (0.9%)
Tumour lysis syndrome	6/112 (5.4%)
Vitamin k deficiency	1/112 (0.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	22/112 (19.6%)
Back pain	25/112 (22.3%)
Bone lesion	1/112 (0.9%)
Bone pain	13/112 (11.6%)
Bursitis	1/112 (0.9%)
Flank pain	3/112 (2.7%)
Groin pain	1/112 (0.9%)
Intervertebral disc degeneration	1/112 (0.9%)
Intervertebral disc protrusion	1/112 (0.9%)
Joint range of motion decreased	1/112 (0.9%)
Joint swelling	2/112 (1.8%)
Kyphosis	1/112 (0.9%)
Limb discomfort	1/112 (0.9%)
Mobility decreased	1/112 (0.9%)
Muscle spasms	7/112 (6.3%)
Muscle tightness	1/112 (0.9%)
Muscle twitching	1/112 (0.9%)
Muscular weakness	4/112 (3.6%)
Musculoskeletal chest pain	5/112 (4.5%)
Musculoskeletal discomfort	6/112 (5.4%)
Musculoskeletal pain	18/112 (16.1%)
Musculoskeletal stiffness	4/112 (3.6%)
Myalgia	11/112 (9.8%)
Myopathy	1/112 (0.9%)
Neck pain	11/112 (9.8%)
Nodule on extremity	2/112 (1.8%)
Osteoarthritis	1/112 (0.9%)
Osteosclerosis	1/112 (0.9%)
Pain in extremity	28/112 (25%)
Pain in jaw	3/112 (2.7%)
Posture abnormal	1/112 (0.9%)
Rhabdomyolysis	1/112 (0.9%)
Spinal osteoarthritis	2/112 (1.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic neoplasm	2/112 (1.8%)
Leukaemia cutis	1/112 (0.9%)
Leukaemic retinopathy	2/112 (1.8%)
Lung neoplasm	6/112 (5.4%)
Spinal haemangioma	1/112 (0.9%)
Uterine leiomyoma	1/112 (0.9%)
Nervous system disorders
Amnesia	3/112 (2.7%)
Aphasia	1/112 (0.9%)
Ataxia	2/112 (1.8%)
Balance disorder	2/112 (1.8%)
Burning sensation	1/112 (0.9%)
Cerebral haemorrhage	1/112 (0.9%)
Cerebrovascular accident	1/112 (0.9%)
Cerebrovascular disorder	1/112 (0.9%)
Cognitive disorder	1/112 (0.9%)
Dementia	1/112 (0.9%)
Disturbance in attention	2/112 (1.8%)
Dizziness	26/112 (23.2%)
Dizziness postural	1/112 (0.9%)
Dysarthria	5/112 (4.5%)
Dysgeusia	8/112 (7.1%)
Embolic stroke	1/112 (0.9%)
Encephalopathy	1/112 (0.9%)
Facial palsy	1/112 (0.9%)
Facial paresis	1/112 (0.9%)
Headache	45/112 (40.2%)
Hyperaesthesia	1/112 (0.9%)
Hypoaesthesia	4/112 (3.6%)
Lethargy	3/112 (2.7%)
Memory impairment	1/112 (0.9%)
Migraine	1/112 (0.9%)
Myoclonus	1/112 (0.9%)
Neuralgia	1/112 (0.9%)
Neuropathy peripheral	6/112 (5.4%)
Orthostatic intolerance	1/112 (0.9%)
Paraesthesia	11/112 (9.8%)
Parosmia	2/112 (1.8%)
Peroneal nerve palsy	1/112 (0.9%)
Poor quality sleep	1/112 (0.9%)
Presyncope	2/112 (1.8%)
Radial nerve palsy	1/112 (0.9%)
Restless legs syndrome	3/112 (2.7%)
Sciatica	1/112 (0.9%)
Sensory loss	1/112 (0.9%)
Sinus headache	4/112 (3.6%)
Somnolence	10/112 (8.9%)
Subarachnoid haemorrhage	1/112 (0.9%)
Syncope	6/112 (5.4%)
Tension headache	1/112 (0.9%)
Tongue paralysis	1/112 (0.9%)
Transient ischaemic attack	1/112 (0.9%)
Tremor	5/112 (4.5%)
Psychiatric disorders
Abnormal behaviour	1/112 (0.9%)
Abnormal dreams	1/112 (0.9%)
Aggression	1/112 (0.9%)
Agitation	8/112 (7.1%)
Anxiety	26/112 (23.2%)
Claustrophobia	1/112 (0.9%)
Confusional state	25/112 (22.3%)
Depressed mood	1/112 (0.9%)
Depression	14/112 (12.5%)
Disorientation	3/112 (2.7%)
Hallucination	4/112 (3.6%)
Hallucination, visual	2/112 (1.8%)
Insomnia	46/112 (41.1%)
Mental status changes	8/112 (7.1%)
Mood altered	1/112 (0.9%)
Nervousness	2/112 (1.8%)
Panic attack	1/112 (0.9%)
Phonophobia	1/112 (0.9%)
Restlessness	1/112 (0.9%)
Renal and urinary disorders
Acute prerenal failure	1/112 (0.9%)
Bladder dilatation	3/112 (2.7%)
Bladder hypertrophy	1/112 (0.9%)
Bladder pain	1/112 (0.9%)
Bladder spasm	3/112 (2.7%)
Chromaturia	1/112 (0.9%)
Dysuria	6/112 (5.4%)
Haematuria	9/112 (8%)
Hydronephrosis	1/112 (0.9%)
Ketonuria	1/112 (0.9%)
Micturition urgency	1/112 (0.9%)
Nephrolithiasis	4/112 (3.6%)
Oliguria	1/112 (0.9%)
Pollakiuria	4/112 (3.6%)
Polyuria	1/112 (0.9%)
Proteinuria	1/112 (0.9%)
Renal cyst	4/112 (3.6%)
Renal failure	8/112 (7.1%)
Renal failure acute	1/112 (0.9%)
Ureteric stenosis	1/112 (0.9%)
Urinary hesitation	1/112 (0.9%)
Urinary incontinence	11/112 (9.8%)
Urinary retention	5/112 (4.5%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/112 (0.9%)
Breast hyperplasia	1/112 (0.9%)
Fibrocystic breast disease	1/112 (0.9%)
Genital rash	1/112 (0.9%)
Oedema genital	1/112 (0.9%)
Pelvic fluid collection	1/112 (0.9%)
Pelvic pain	1/112 (0.9%)
Penile swelling	2/112 (1.8%)
Prostatomegaly	1/112 (0.9%)
Scrotal haematocoele	1/112 (0.9%)
Vaginal haemorrhage	3/112 (2.7%)
Vulvovaginal discomfort	1/112 (0.9%)
Vulvovaginal pruritus	1/112 (0.9%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/112 (0.9%)
Allergic sinusitis	1/112 (0.9%)
Atelectasis	14/112 (12.5%)
Cough	34/112 (30.4%)
Dysphonia	1/112 (0.9%)
Dyspnoea	33/112 (29.5%)
Dyspnoea exertional	3/112 (2.7%)
Dyspnoea paroxysmal nocturnal	1/112 (0.9%)
Egobronchophony	1/112 (0.9%)
Emphysema	1/112 (0.9%)
Epistaxis	30/112 (26.8%)
Haemoptysis	17/112 (15.2%)
Hiccups	4/112 (3.6%)
Hypoxia	17/112 (15.2%)
Increased upper airway secretion	1/112 (0.9%)
Lung consolidation	3/112 (2.7%)
Lung disorder	1/112 (0.9%)
Lung infiltration	5/112 (4.5%)
Nasal congestion	7/112 (6.3%)
Nasal discomfort	1/112 (0.9%)
Nasal dryness	1/112 (0.9%)
Obstructive airways disorder	1/112 (0.9%)
Oropharyngeal blistering	3/112 (2.7%)
Oropharyngeal pain	15/112 (13.4%)
Orthopnoea	1/112 (0.9%)
Painful respiration	5/112 (4.5%)
Paranasal sinus hypersecretion	4/112 (3.6%)
Pharyngeal erythema	4/112 (3.6%)
Pleural effusion	26/112 (23.2%)
Pleuritic pain	5/112 (4.5%)
Pneumonitis	3/112 (2.7%)
Postnasal drip	4/112 (3.6%)
Productive cough	4/112 (3.6%)
Prolonged expiration	1/112 (0.9%)
Pulmonary alveolar haemorrhage	1/112 (0.9%)
Pulmonary congestion	1/112 (0.9%)
Pulmonary granuloma	1/112 (0.9%)
Pulmonary haemorrhage	2/112 (1.8%)
Pulmonary hypertension	2/112 (1.8%)
Pulmonary oedema	14/112 (12.5%)
Rales	19/112 (17%)
Respiratory acidosis	1/112 (0.9%)
Respiratory alkalosis	1/112 (0.9%)
Respiratory distress	2/112 (1.8%)
Rhinitis allergic	1/112 (0.9%)
Rhinorrhoea	6/112 (5.4%)
Rhonchi	3/112 (2.7%)
Sinus congestion	8/112 (7.1%)
Sinus disorder	2/112 (1.8%)
Sputum discoloured	1/112 (0.9%)
Tachypnoea	9/112 (8%)
Upper airway obstruction	1/112 (0.9%)
Wheezing	10/112 (8.9%)
Skin and subcutaneous tissue disorders
Acute febrile neutrophilic dermatosis	1/112 (0.9%)
Alopecia	3/112 (2.7%)
Blister	3/112 (2.7%)
Blood blister	3/112 (2.7%)
Decubitus ulcer	7/112 (6.3%)
Dermatitis acneiform	2/112 (1.8%)
Dermatitis allergic	1/112 (0.9%)
Drug eruption	3/112 (2.7%)
Dry skin	9/112 (8%)
Ecchymosis	19/112 (17%)
Erythema	14/112 (12.5%)
Exfoliative rash	3/112 (2.7%)
Hyperhidrosis	14/112 (12.5%)
Increased tendency to bruise	2/112 (1.8%)
Leukoplakia	1/112 (0.9%)
Nail disorder	1/112 (0.9%)
Night sweats	7/112 (6.3%)
Palmar erythema	1/112 (0.9%)
Palmar-plantar erythrodysaesthesia syndr	1/112 (0.9%)
Periorbital oedema	3/112 (2.7%)
Petechiae	29/112 (25.9%)
Pruritus	26/112 (23.2%)
Pruritus generalised	1/112 (0.9%)
Purpura	2/112 (1.8%)
Rash	52/112 (46.4%)
Rash erythematous	3/112 (2.7%)
Rash generalised	15/112 (13.4%)
Rash macular	6/112 (5.4%)
Rash maculo-papular	5/112 (4.5%)
Rash papular	4/112 (3.6%)
Rash pruritic	6/112 (5.4%)
Skin disorder	1/112 (0.9%)
Skin exfoliation	1/112 (0.9%)
Skin haemorrhage	1/112 (0.9%)
Skin irritation	2/112 (1.8%)
Skin lesion	6/112 (5.4%)
Skin mass	1/112 (0.9%)
Skin necrosis	2/112 (1.8%)
Skin oedema	1/112 (0.9%)
Skin ulcer	2/112 (1.8%)
Swelling face	1/112 (0.9%)
Urticaria	5/112 (4.5%)
Surgical and medical procedures
Fasciotomy	1/112 (0.9%)
Leg amputation	1/112 (0.9%)
Vascular disorders
Aortic aneurysm	3/112 (2.7%)
Aortic calcification	1/112 (0.9%)
Aortic stenosis	1/112 (0.9%)
Arteriosclerosis	2/112 (1.8%)
Capillary leak syndrome	1/112 (0.9%)
Deep vein thrombosis	3/112 (2.7%)
Flushing	13/112 (11.6%)
Haematoma	8/112 (7.1%)
Haemorrhage	1/112 (0.9%)
Hot flush	1/112 (0.9%)
Hypertension	22/112 (19.6%)
Hypertensive crisis	1/112 (0.9%)
Hypotension	32/112 (28.6%)
Orthostatic hypertension	1/112 (0.9%)
Orthostatic hypotension	6/112 (5.4%)
Pallor	4/112 (3.6%)
Peripheral coldness	1/112 (0.9%)
Phlebitis	1/112 (0.9%)
Thrombophlebitis superficial	1/112 (0.9%)
Thrombosis	1/112 (0.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

In multi-site studies, PI can publish after Genzyme publishes or 18 months after study completion. PI gives Genzyme a draft 60 days before publication. Genzyme can ask that confidential information be removed, and can defer publication another 60 days upon notifying PI that it will file a patent application on inventions contained in the draft.