VOSIFI: Voriconazole for Secondary Prophylaxis of Invasive Fungal Infections in Patients With Allogeneic Stem Cell Transplants

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00143312
• Collaborator: European Society for Blood and Marrow Transplantation (Other)
• Enrollment: 45
• Locations: 17
• Arm: 1
• Duration (Months): 37.9
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To prevent recurrence of invasive fungal infection in patients with allogeneic stem cell transplants

Condition or Disease	Intervention/Treatment	Phase
Prophylaxis Of Invasive Fungal Infections	Drug: voriconazole	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Prospective, Open-Label, Non-Comparative, Multicenter Study for the Secondary Prophylaxis of Invasive Fungal Infections (IFI) With Voriconazole in Patients With Allogeneic Stem Cell Transplants (SCT).
• Study Start Date: Feb 1, 2005
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: voriconazole; Voriconazole is given to patients at least 48 hours after chemotherapy

Outcome Measures

Primary Outcome Measures

1. Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Prophylaxis Until 12-month Follow-up Visit [12 months]

   Number of participants developing a proven or probable IFI from start of voriconazole prophylaxis until 12-month follow up

Secondary Outcome Measures

1. Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Prophylaxis Until 6-month Follow-up Visit [6 months]

   Number of participants developing a proven or probable IFI from start of voriconazole prophylaxis until 6-month follow up

2. Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Voriconazole Prophylaxis Until End of Prophylaxis Visit [150 days]

   Number of participants developing a proven or probable IFI from start of voriconazole prophylaxis until the End of Prophylaxis visit

3. Time to Occurrence of Proven or Probable Invasive Fungal Infection (IFI) [12 months]

   Time to occurrence of proven or probable IFI from the start of voriconazole prophylaxis. Time to occurrence is strictly time to recorded diagnosis of IFI since the exact day on which the IFI began will not be known.

4. Time to Occurrence of Proven or Probable New (New Pathogen) Invasive Fungal Infection (IFI) [12 months]

   Time to occurrence of proven or probable new (new pathogen) IFI from the start of voriconazole prophylaxis. Time to occurrence is strictly time to recorded diagnosis of IFI.

5. Time to Occurrence of Proven or Probable Recurrent Invasive Fungal Infection (IFI) (Same Pathogen as Previous Baseline IFI) [12 months]

   Time to occurrence of proven or probable recurrent (same pathogen as baseline) IFI from the start of voriconazole prophylaxis. Time to occurrence is strictly time to recorded diagnosis of IFI. The pathogen identified as the positive culture recorded nearest to, but not after, the proven or probable IFI, was assumed to be responsible for the IFI.

6. Survival Without Proven or Probable Invasive Fungal Infection (IFI) [6 months, 12 months]

   Number of participants who survive (ie., are alive) without proven or probable IFI at each of the 6 and 12 month follow-up visits

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients with proven or probable IFI in previous 12 months receiving an allogenic stem cell transplant for any haematological disease

Exclusion Criteria:

• Pregnant or lactating women

• Severe disease other tham the underlying condition

• Active, symptomatic uncontrolled Invasive Fungal Infection

• Any evidence of active fungal disease as defined by MSG-EORTC criteria

• Concomitant use of Voriconazole 36 hours before chemotherapy until 48 hours after chemotherapy

• Other medical conditions, including HIV positive serology that would interfere with the evaluation of therapeutic response or safety of study drug

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Leuven		Belgium	3000
2	Pfizer Investigational Site	Marseille	Cedex 09	France	13273
3	Pfizer Investigational Site	Creteil		France	94010
4	Pfizer Investigational Site	Nantes		France	44035 cedex
5	Pfizer Investigational Site	Pessac		France	33600
6	Pfizer Investigational Site	Strasbourg		France	67098
7	Pfizer Investigational Site	Koeln		Germany	50937
8	Pfizer Investigational Site	Mainz		Germany	55101
9	Pfizer Investigational Site	Wuerzburg		Germany	97070
10	Pfizer Investigational Site	Lisboa		Portugal	1099-023
11	Pfizer Investigational Site	Barcelona		Spain	08025
12	Pfizer Investigational Site	Barcelona		Spain	08036
13	Pfizer Investigational Site	Madrid		Spain	28006
14	Pfizer Investigational Site	Stockholm		Sweden	141 86
15	Pfizer Investigational Site	CH-4031 Basel		Switzerland
16	Pfizer Investigational Site	London		United Kingdom	W12 0NN
17	Pfizer Investigational Site	Manchester		United Kingdom	M20 4BX

Sponsors and Collaborators

• Pfizer
• European Society for Blood and Marrow Transplantation

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00143312
• Other Study ID Numbers: A1501038
• First Posted: Sep 2, 2005
• Last Update Posted: Oct 6, 2009
• Last Verified: Sep 1, 2009

• Keywords provided by , ,: Invasive Fungal Infection, Allogenic Stem Cell Transplant, prophylaxis, leukemia, voriconazole
• Additional relevant MeSH terms: Infections; Communicable Diseases; Mycoses; Invasive Fungal Infections; Voriconazole

Study Results

Participant Flow

Pre-assignment Detail	Subjects with proven or probable Invasive Fungal Infection (IFI) in the previous 12 months, who were receiving an allogeneic Stem Cell Transplant (SCT) for any hematologic disease, were enrolled into the study if all other inclusion/exclusion criteria were met.

Arm/Group Title	Voriconazole
Arm/Group Description	All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed <40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h.
Period Title: Overall Study
STARTED	45
COMPLETED	29
NOT COMPLETED	16

Baseline Characteristics

Arm/Group Title	Voriconazole
Arm/Group Description	All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed <40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h.
Overall Participants	45
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.4 (14.1)
Sex: Female, Male (Count of Participants)
Female	17 37.8%
Male	28 62.2%

Outcome Measures

1. Primary Outcome

Title	Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Prophylaxis Until 12-month Follow-up Visit
Description	Number of participants developing a proven or probable IFI from start of voriconazole prophylaxis until 12-month follow up
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Complete case analysis (ie, outcome must be observed and/or subject must be evaluable for entire period of interest) using modified intent-to-treat (MITT) population (ie, subjects had at least 1 dose of voriconazole & at least 1 post-enrollment efficacy assessment & previous diagnosis of proven or probable IFI, confirmed by Data Review Committee).

Arm/Group Title	Voriconazole
Arm/Group Description	All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed <40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h.
Measure Participants	30
Number [participants]	3 6.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Voriconazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Crude IFI Rate (percent) at 12 months
	Estimated Value	7
	Confidence Interval	() 95%; 2 to 19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Voriconazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	IFI Rate (percent) at 12 months
	Estimated Value	10
	Confidence Interval	() 95%; 2 to 27
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Prophylaxis Until 6-month Follow-up Visit
Description	Number of participants developing a proven or probable IFI from start of voriconazole prophylaxis until 6-month follow up
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Complete case analysis (ie, outcome must be observed and/or subject must be evaluable for entire period of interest) using modified intent-to-treat (MITT) population (ie, subjects had at least 1 dose of voriconazole & at least 1 post-enrollment efficacy assessment & previous diagnosis of proven or probable IFI, confirmed by Data Review Committee).

Arm/Group Title	Voriconazole
Arm/Group Description	All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed <40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h.
Measure Participants	34
Number [participants]	3 6.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Voriconazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	IFI Rate (percent) at 6 months
	Estimated Value	8.82
	Confidence Interval	() 95%; 2 to 24
	Parameter Dispersion	Type: Value:
	Estimation Comments	Exact 95% Confidence Interval For Proportion; Expressed as a percentage

3. Secondary Outcome

Title	Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Voriconazole Prophylaxis Until End of Prophylaxis Visit
Description	Number of participants developing a proven or probable IFI from start of voriconazole prophylaxis until the End of Prophylaxis visit
Time Frame	150 days

Outcome Measure Data

Analysis Population Description

Complete case analysis (ie, outcome must be observed and/or subject must be evaluable for entire period of interest) using modified intent-to-treat (MITT) population (ie, subjects had at least 1 dose of voriconazole & at least 1 post-enrollment efficacy assessment & previous diagnosis of proven or probable IFI, confirmed by Data Review Committee).

Arm/Group Title	Voriconazole
Arm/Group Description	All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed <40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h.
Measure Participants	34
Number [participants]	3 6.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Voriconazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	IFI Rate (percent) at End of Prophylaxis
	Estimated Value	8.82
	Confidence Interval	() 95%; 2 to 24
	Parameter Dispersion	Type: Value:
	Estimation Comments	Exact 95% Confidence Interval For Proportion; Expressed as a percentage

4. Secondary Outcome

Title	Time to Occurrence of Proven or Probable Invasive Fungal Infection (IFI)
Description	Time to occurrence of proven or probable IFI from the start of voriconazole prophylaxis. Time to occurrence is strictly time to recorded diagnosis of IFI since the exact day on which the IFI began will not be known.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (MITT) population (considered evaluable for efficacy) consisted of all subjects who had at least 1 dose of voriconazole & at least 1 post-enrollment efficacy assessment & had a previous diagnosis of proven or probable IFI, confirmed by the Data Review Committee. Three subjects in the MITT population experienced an IFI.

Arm/Group Title	Voriconazole
Arm/Group Description	All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed <40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h.
Measure Participants	42
time to recurrent IFI (first subject)	6
time to recurrent IFI (second subject)	22
time to recurrent IFI (third subject)	81

5. Secondary Outcome

Title	Time to Occurrence of Proven or Probable New (New Pathogen) Invasive Fungal Infection (IFI)
Description	Time to occurrence of proven or probable new (new pathogen) IFI from the start of voriconazole prophylaxis. Time to occurrence is strictly time to recorded diagnosis of IFI.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (MITT) population (considered evaluable for efficacy) consisted of all subjects who had at least 1 dose of voriconazole & at least 1 post-enrollment efficacy assessment & had a previous diagnosis of proven or probable IFI, confirmed by the Data Review Committee. One subject in the MITT population experienced a new IFI.

Arm/Group Title	Voriconazole
Arm/Group Description	All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed <40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h.
Measure Participants	42
Number [days]	81

6. Secondary Outcome

Title	Time to Occurrence of Proven or Probable Recurrent Invasive Fungal Infection (IFI) (Same Pathogen as Previous Baseline IFI)
Description	Time to occurrence of proven or probable recurrent (same pathogen as baseline) IFI from the start of voriconazole prophylaxis. Time to occurrence is strictly time to recorded diagnosis of IFI. The pathogen identified as the positive culture recorded nearest to, but not after, the proven or probable IFI, was assumed to be responsible for the IFI.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (MITT) population (considered evaluable for efficacy) consisted of all subjects who had at least 1 dose of voriconazole & at least 1 post-enrollment efficacy assessment & had a previous diagnosis of proven or probable IFI, confirmed by the Data Review Committee. Two subjects experienced a recurrent proven or probable IFI.

Arm/Group Title	Voriconazole
Arm/Group Description	All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed <40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h.
Measure Participants	42
time to IFI (first subject)	6
time to IFI (second subject)	22

7. Secondary Outcome

Title	Survival Without Proven or Probable Invasive Fungal Infection (IFI)
Description	Number of participants who survive (ie., are alive) without proven or probable IFI at each of the 6 and 12 month follow-up visits
Time Frame	6 months, 12 months

Outcome Measure Data

Analysis Population Description

Complete case analysis using MITT population (ie, all subjects who had at least 1 dose of study medication & at least 1 post-enrollment efficacy assessment & a previous diagnosis of proven or probable IFI, confirmed by Data Review Committee) & either provided an IFI assessment at follow-up visit, died or experienced an IFI before that visit.

Arm/Group Title	Voriconazole
Arm/Group Description	All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed <40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h.
Measure Participants	39
survived free of IFI until 6 months	31 68.9%
survived free of IFI until 12 months	27 60%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Voriconazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	survive free of IFI (percent): 6 months
	Estimated Value	79
	Confidence Interval	() 95%; 64 to 91
	Parameter Dispersion	Type: Value:
	Estimation Comments	Exact 95% Confidence Interval For Proportion; Expressed as a percentage

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Voriconazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	survive free of IFI (percent): 12 months
	Estimated Value	69
	Confidence Interval	() 95%; 52 to 83
	Parameter Dispersion	Type: Value:
	Estimation Comments	Exact 95% Confidence Interval For Proportion; Expressed as a percentage

Adverse Events

Arm/Group Title	Voriconazole
Arm/Group Description	All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed <40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h.
All Cause Mortality
	Voriconazole
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Voriconazole
	Affected / at Risk (%)	# Events
Total	23/45 (51.1%)
Blood and lymphatic system disorders
Haemolysis	1/45 (2.2%)
Pancytopenia	1/45 (2.2%)
Thrombocytopenia	1/45 (2.2%)
Cardiac disorders
Atrial fibrillation	1/45 (2.2%)
Palpitations	1/45 (2.2%)
Tachycardia	1/45 (2.2%)
Eye disorders
Eye swelling	1/45 (2.2%)
Gastrointestinal disorders
Abdominal pain	1/45 (2.2%)
Diarrhoea	2/45 (4.4%)
Nausea	1/45 (2.2%)
Vomiting	3/45 (6.7%)
General disorders
Disease progression	1/45 (2.2%)
Pyrexia	2/45 (4.4%)
Hepatobiliary disorders
Cholecystitis	1/45 (2.2%)
Cholestasis	1/45 (2.2%)
Hepatitis toxic	1/45 (2.2%)
Hepatomegaly	1/45 (2.2%)
Hepatotoxicity	2/45 (4.4%)
Hyperbilirubinaemia	1/45 (2.2%)
Immune system disorders
Graft versus host disease	2/45 (4.4%)
Infections and infestations
Cytomegalovirus infection	1/45 (2.2%)
Diarrhoea infectious	1/45 (2.2%)
Encephalitis herpes	1/45 (2.2%)
Pneumonia	1/45 (2.2%)
Sepsis	2/45 (4.4%)
Investigations
Blood creatine increased	1/45 (2.2%)
Electrocardiogram change	1/45 (2.2%)
Liver function test abnormal	1/45 (2.2%)
Sputum culture positive	1/45 (2.2%)
Weight increased	1/45 (2.2%)
Metabolism and nutrition disorders
Hyperglycaemia	1/45 (2.2%)
Musculoskeletal and connective tissue disorders
Myalgia	1/45 (2.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia recurrent	1/45 (2.2%)
Central nervous system leukaemia	1/45 (2.2%)
Nervous system disorders
Facial paresis	1/45 (2.2%)
Headache	1/45 (2.2%)
Loss of consciousness	1/45 (2.2%)
Psychiatric disorders
Hallucination	1/45 (2.2%)
Renal and urinary disorders
Renal failure	1/45 (2.2%)
Respiratory, thoracic and mediastinal disorders
Productive cough	1/45 (2.2%)
Pulmonary oedema	1/45 (2.2%)
Skin and subcutaneous tissue disorders
Erythema	1/45 (2.2%)
Vascular disorders
Hypertension	1/45 (2.2%)
Hypotension	1/45 (2.2%)
Venoocclusive disease	1/45 (2.2%)
Other (Not Including Serious) Adverse Events
	Voriconazole
	Affected / at Risk (%)	# Events
Total	42/45 (93.3%)
Blood and lymphatic system disorders
Anaemia	7/45 (15.6%)
Febrile neutropenia	8/45 (17.8%)
Neutropenia	3/45 (6.7%)
Thrombocytopenia	7/45 (15.6%)
Eye disorders
Conjunctivitis	3/45 (6.7%)
Gastrointestinal disorders
Abdominal pain	7/45 (15.6%)
Abdominal pain upper	6/45 (13.3%)
Constipation	5/45 (11.1%)
Diarrhoea	15/45 (33.3%)
Dyspepsia	3/45 (6.7%)
Nausea	5/45 (11.1%)
Vomiting	13/45 (28.9%)
General disorders
Asthenia	4/45 (8.9%)
Chills	5/45 (11.1%)
Fatigue	4/45 (8.9%)
Mucosal inflammation	17/45 (37.8%)
Oedema peripheral	5/45 (11.1%)
Pyrexia	13/45 (28.9%)
Hepatobiliary disorders
Cholestasis	3/45 (6.7%)
Hepatotoxicity	3/45 (6.7%)
Immune system disorders
Acute graft versus host disease	3/45 (6.7%)
Chronic graft versus host disease	3/45 (6.7%)
Graft versus host disease	12/45 (26.7%)
Infections and infestations
Cytomegalovirus infection	4/45 (8.9%)
Sinusitis	3/45 (6.7%)
Injury, poisoning and procedural complications
Transfusion reaction	3/45 (6.7%)
Investigations
Liver function test abnormal	4/45 (8.9%)
Weight decreased	3/45 (6.7%)
Metabolism and nutrition disorders
Anorexia	4/45 (8.9%)
Hypokalaemia	3/45 (6.7%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	3/45 (6.7%)
Pain in extremity	3/45 (6.7%)
Nervous system disorders
Headache	13/45 (28.9%)
Psychiatric disorders
Anxiety	3/45 (6.7%)
Hallucination	3/45 (6.7%)
Insomnia	7/45 (15.6%)
Sleep disorder	3/45 (6.7%)
Respiratory, thoracic and mediastinal disorders
Cough	3/45 (6.7%)
Skin and subcutaneous tissue disorders
Erythema	5/45 (11.1%)
Rash	6/45 (13.3%)
Vascular disorders
Hypertension	8/45 (17.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Pfizer has the right to review disclosures, requesting a delay of < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential info other than study results.