Subcutaneous Alemtuzumab (CAMPATH®, MabCampath®) in Relapsed/Refractory B-Cell Chronic Lymphocytic Leukemia

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00328198
• Collaborator: Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma (Industry)
• Enrollment: 86
• Locations: 21
• Arms: 2
• Duration (Months): 63
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a Phase II, open-label, prospective, multicenter study to evaluate the efficacy and safety of subcutaneously administered alemtuzumab (CAMPATH, MabCampath) as therapy for patients with relapsed or refractory B-CLL who have been previously treated.

Condition or Disease	Intervention/Treatment	Phase
B-Cell Chronic Lymphocytic Leukemia (B-CLL)	Biological: Alemtuzumab; Biological: Alemtuzumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 86 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial to Evaluate the Efficacy and Safety of Subcutaneously Administered Alemtuzumab (CAMPATH®, MabCampath®) in Patients With Previously Treated B-Cell Chronic Lymphocytic Leukemia
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Aug 1, 2011
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose escalation Alemtuzumab is administered using escalating doses and alternating injection sites. The dose is escalated as tolerated using 3mg, 10mg, and 30mg administered subcutaneously (SC) (if tolerated).	Biological: Alemtuzumab; Alemtuzumab is administered using escalating doses and alternating injection sites. The dose is escalated as tolerated using 3mg, 10mg, and 30mg administered subcutaneously (SC) (if tolerated). When escalation to 30 mg is tolerated, all subsequent doses are administered at 30 mg SC 3 times per week at alternating injection sites for up to 18 weeks. Part 1 of the study: The first 20 patients will be randomized to either Arm 1 (dose escalation) or Arm 2 (no escalation). Part 1 of the study has been completed; no additional patients will be enrolled in Part 1. An assigned review panel has reviewed the safety data from Part 1 and determined that all patients will be enrolled and treated under a no escalation schedule for Part 2 of the study.; Other Names: Campath®, MabCampath®
Experimental: No escalation Alemtuzumab treatment is started immediately at the 30mg dose (with no escalation period), administered subcutaneously at alternating injection sites 3 times per week for up to 18 weeks.	Biological: Alemtuzumab; Alemtuzumab treatment is started immediately at the 30mg dose (with no escalation period), administered SC at alternating injection sites 3 times per week for up to 18 weeks. Part 2 of the study: All patients are currently being enrolled under the no escalation schedule for Part 2 of the study. All patients in Part 2 will be treated with 30mg of alemtuzumab (with no escalation period) administered SC (at alternating injection sites) 3 times per week (e.g., Monday, Wednesday, Friday) for up to 18 weeks. Alemtuzumab is to be administered in a supervised medical setting on an outpatient basis for the first three weeks, after which some study centers may allow a home administration option, with one weekly clinic visit. Under the home administration option, alemtuzumab may be administered by the patient or care giver if the patient meets conditions specified in the protocol guidelines for home administration.; Other Names: Campath®, MabCampath®

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Best Disease Response as Determined by the Independent Response Review Panel (IRRP) [up to 44 weeks]

   Participants were evaluated by the IRRP according to National Cancer Institute (NCI) 1996 response criteria. The best response observed during the study is summarized. Response categories include Complete Response (CR) with normal physical exam, marrow cells and blood values, Partial Response (PR) with a >= 50% decrease from baseline in lymphocytes, lymphadenopathy and liver or spleen exam, Stable Disease (SD) without significant progression from baseline, or Progressive Disease (PD) with increased size/number of nodes, size of liver or spleen, increase in lymphocytes, aggressive histology.

2. Percentage of Participants Who Had an Overall Response (OR) as Determined by the Independent Response Review Panel (IRRP) [up to 44 weeks]

   Participants were evaluated by the IRRP according to National Cancer Institute (NCI) 1996 response criteria. The percentage of participants whose best response observed during the study was either a Complete Response (CR) or a Partial Response (PR). Overall Response (OR) = CR + PR. A Complete Response (CR) exhibits a normal physical exam, marrow cells and blood values. A Partial Response (PR) has a >= 50% decrease from baseline in lymphocytes, lymphadenopathy and liver or spleen exam.

Secondary Outcome Measures

1. Kaplan-Meier Estimates of Progression Free Survival as Determined by the Independent Response Review Panel (IRRP) [up to 5 years]

   Progression-free survival was defined as the number of days from the date of first treatment to the date of first objective documentation of progressive disease (PD) as determined by the IRRP, or death due to any cause. Results are expressed in months. Progressive Disease (PD) was defined as an increase in size/number of nodes, size of liver or spleen, increase in lymphocytes, or aggressive histology.

2. Kaplan-Meier Estimates of Duration of Response as Determined by the Independent Response Review Panel (IRRP) [up to 5 years]

   Duration of response was analyzed for participants who achieved a complete response (CR) or partial response (PR) and was defined as the number of days from the first date of documented response to the date of progressive disease (PD) as determined by IRRP or death due to any cause. Results are stated in months. Progressive Disease (PD) was defined as an increase in size/number of nodes, size of liver or spleen, increase in lymphocytes, or aggressive histology.

3. Kaplan-Meier Estimates of Overall Survival [up to 5 years]

   Overall survival was defined as the time in days from the date of first treatment to the date of death due to any cause for all participants. Results are stated in months.

4. Participants With a Minimal Residual Disease (MRD) Status of Negative [44 weeks]

   MRD negativity represents a very positive response outcome. MRD negativity in this report was defined by the absence of tumor cells in bone marrow, using 4-color flow cytometry. All patients are evaluated for treatment response based on National Cancer Institute Working Group (NCIWG) criteria. Of patients who have achieved a clinical complete response (CR) or partial response (PR) that met National Cancer Institute Working Group (NCIWG) criteria of CR except blood recovery, a bone marrow sample was taken for flow cytometry measure of MRD negativity.

5. Participants With Treatment-Emergent Adverse Events (TEAE) [up to 18 weeks of treatment plus 45 days]

   Number of participants with treatment-emergent adverse events (TEAEs). AEs were graded by the investigator using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and were assessed for relatedness to study treatment (5 point scale from 'not related' to 'definitely related') and severity (5 point scale with grade 5 being most severe). Categories reported include participant counts for treatment-emergent AEs, injection site reactions, AEs for infections, serious AEs, AEs causing discontinuation of study drug(s), deaths and severity.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• A diagnosis of B-cell chronic lymphocytic leukemia (B-CLL); according to the National Cancer Institute Working Group (NCI WG) Criteria.

• World Health Organization (WHO) performance status of 0, 1, or 2.

• Life expectancy ≥ 12 weeks.

• Previous therapy with at least one but no more than 5 regimens (single agent or combination regimen). One therapy regimen is defined as consecutive, contiguous cycles of the same drug(s) with no treatment interruptions lasting > 3 months.

• Patient requires treatment for CLL per the following criteria: -Rai stage III or IV; -Rai stage 0-II with at least one of the following - evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia; Massive (i.e. greater than 6 cm below the left costal margin) or progressive splenomegaly; Progressive lymphocytosis with an increase of greater than 50% over a 2-month period or an anticipated doubling time of less than 6 months; Lymphocyte count > 100*10^9/L; B symptoms.

• More than 3 weeks since prior chemotherapy. Patient must have recovered from the acute side effects incurred as a result of previous therapy.

• More than 3 weeks since using investigational agents. Patient must have recovered from the acute side effects incurred as a result of previous therapy.

• Serum creatinine and conjugated (direct) bilirubin less than or equal to 2 times the institutional upper limit of normal (ULN) unless secondary to direct infiltration of the liver with CLL.

• Female patients with childbearing potential must have a negative pregnancy test (serum or urine) within 2 weeks of first dose of study drug(s). All patients must agree to use an effective contraceptive method while on study treatment, if appropriate, and for a minimum of 6 months following study therapy.

• Signed, written informed consent (in the US, includes The Health Insurance Portability and Accountability Act of 1996 (HIPAA) authorization)

Exclusion Criteria:

• Positive Coombs test and evidence of active hemolysis.

• Platelet count less than 50*10^9/L without splenomegaly.

• History of anaphylaxis following exposure to rat or mouse derived CDR-grafted humanized monoclonal antibodies.

• Previously treated with CAMPATH.

• Previous bone marrow transplant.

• Known central nervous system (CNS) involvement with B-CLL

• Active infection, including human immunodeficiency virus (HIV) positive.

• Active second malignancy.

• Recent documented history (within 2 years) of active tuberculosis (TB), current active TB infection, currently receiving anti-tuberculous medication (e.g., INH, rifampin, streptomycin, pyrazinamide, or others).

• Active hepatitis or a history of prior viral hepatitis B or hepatitis C, or positive hepatitis B serologies. Patients with a positive hepatitis B surface antibody (HBsAb) test with a documented history of prior hepatitis B immunization are eligible as long as other criteria are met (i.e. negative tests for: hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) and hepatitis C virus antibody (HCVAb)).

• Other severe, concurrent diseases (e.g., cardiac or pulmonary disease), mental disorders, or major organ malfunction (liver, kidney) that could interfere with the patient ability to participate in the study.

• Pregnant or nursing women.

• Cytomegalovirus (CMV) positive by polymerase chain reaction (PCR) (above the level of detection). A patient that is PCR positive will require treatment to reduce the viral load to a non-detectable level; but such a patient may be considered for study entry once the infection has been treated.

• Medical condition requiring chronic use of oral corticosteroids at a dose higher than physiologic replacement.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Moores Cancer Center	La Jolla	California	United States	92093-0820
2	Wilshire Oncology Medical Group	La Verne	California	United States	91750
3	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Aurora	Colorado	United States	80045
4	Rocky Mountain Cancer Centers	Colorado Springs	Colorado	United States	80909
5	North Mississippi Hematology & Oncology Associates, Ltd.	Tupelo	Mississippi	United States	38801
6	Mid Ohio Oncology Hematology, Inc.	Columbus	Ohio	United States	43213
7	Joe Arrington Cancer Center	Lubbock	Texas	United States	79140
8	Academisch Ziekenhuis der Vrije Universiteit Brussel	Brussels		Belgium	1090
9	Cliniques Universitaires Saint-Luc	Brussels		Belgium
10	Universitair Ziekenhuis Gent	Gent		Belgium	B-9000
11	Universitair Ziekenhuis Leuven	Leuven		Belgium	B-3000
12	University Hospital Brno	Brno		Czech Republic	625 00
13	University Hospital Hradec Kralove (UH HK)	Hradec Kralove		Czech Republic
14	Hopital Hotel-Dieu	Clermont-Ferrand		France	63058
15	Hopital Claude Huriez	Lille		France	59037
16	Hopital Hotel-Dieu, CHU de Nantes-Service d'Hematologie Clinique	Nantes		France
17	Institute of Hematology, Clinical Centre of Serbia	Belgrade		Serbia	11 000
18	Clinic of Hematology, Clinical Centre Vojvodina Novi Sad	Novi Sad		Serbia	21000
19	Leeds General Infirmary	Leeds		United Kingdom	LS1 3EX
20	Royal Liverpool and Broadgreen Hospitals	Liverpool		United Kingdom	L7 8XP
21	Nottingham City Hospital	Nottingham		United Kingdom	NG5 1PB

Sponsors and Collaborators

• Genzyme, a Sanofi Company
• Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma

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: NCT00328198
• Other Study ID Numbers: CAM203; 2005-005074-69
• First Posted: May 19, 2006
• Last Update Posted: Mar 13, 2014
• Last Verified: Feb 1, 2014

• Keywords provided by Genzyme, a Sanofi Company: CAMPATH; Alemtuzumab; Leukemia; MabCampath; Chronic; Subcutaneous; CLL; C-CLL; Relapsed; Refractory; Chronic Lymphocytic Leukemia
• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Alemtuzumab

Study Results

Participant Flow

Pre-assignment Detail	109 patients screened and 86 enrolled and treated.

Arm/Group Title	Alemtuzumab 30mg
Arm/Group Description	Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Period Title: Treatment
STARTED	86
COMPLETED	48
NOT COMPLETED	38
Period Title: Treatment
STARTED	78
COMPLETED	43
NOT COMPLETED	35

Baseline Characteristics

Arm/Group Title	Alemtuzumab 30mg
Arm/Group Description	Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Overall Participants	86
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.32 (9.035)
Sex: Female, Male (Count of Participants)
Female	29 33.7%
Male	57 66.3%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	0 0%
Asian	1 1.2%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 2.3%
White	82 95.3%
Other	1 1.2%
Current Rai Stage (participants) [Number]
Rai Stage 0	7 8.1%
Rai Stage I	10 11.6%
Rai Stage II	22 25.6%
Rai Stage III	7 8.1%
Rai Stage IV	40 46.5%
Current Binet Stage (participants) [Number]
Stage A	20 23.3%
Stage B	22 25.6%
Stage C	44 51.2%
World Health Organization (WHO) Performance (participants) [Number]
0	55 64%
1	28 32.6%
2	3 3.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Best Disease Response as Determined by the Independent Response Review Panel (IRRP)
Description	Participants were evaluated by the IRRP according to National Cancer Institute (NCI) 1996 response criteria. The best response observed during the study is summarized. Response categories include Complete Response (CR) with normal physical exam, marrow cells and blood values, Partial Response (PR) with a >= 50% decrease from baseline in lymphocytes, lymphadenopathy and liver or spleen exam, Stable Disease (SD) without significant progression from baseline, or Progressive Disease (PD) with increased size/number of nodes, size of liver or spleen, increase in lymphocytes, aggressive histology.
Time Frame	up to 44 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Alemtuzumab 30mg
Arm/Group Description	Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Measure Participants	86
Overall response (CR+PR)	37 43%
Complete response (CR)	5 5.8%
Partial response (PR)	32 37.2%
Stable disease (SD)	24 27.9%
Progressive disease (PD)	4 4.7%
Not Evaluable (NE)	21 24.4%

2. Secondary Outcome

Title	Kaplan-Meier Estimates of Progression Free Survival as Determined by the Independent Response Review Panel (IRRP)
Description	Progression-free survival was defined as the number of days from the date of first treatment to the date of first objective documentation of progressive disease (PD) as determined by the IRRP, or death due to any cause. Results are expressed in months. Progressive Disease (PD) was defined as an increase in size/number of nodes, size of liver or spleen, increase in lymphocytes, or aggressive histology.
Time Frame	up to 5 years

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Alemtuzumab 30mg
Arm/Group Description	Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Measure Participants	86
Median (95% Confidence Interval) [months]	12.43

3. Secondary Outcome

Title	Kaplan-Meier Estimates of Duration of Response as Determined by the Independent Response Review Panel (IRRP)
Description	Duration of response was analyzed for participants who achieved a complete response (CR) or partial response (PR) and was defined as the number of days from the first date of documented response to the date of progressive disease (PD) as determined by IRRP or death due to any cause. Results are stated in months. Progressive Disease (PD) was defined as an increase in size/number of nodes, size of liver or spleen, increase in lymphocytes, or aggressive histology.
Time Frame	up to 5 years

Outcome Measure Data

Analysis Population Description

Participants who had a complete response or a partial response

Arm/Group Title	Alemtuzumab 30mg
Arm/Group Description	Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Measure Participants	37
Median (95% Confidence Interval) [months]	11.09

4. Secondary Outcome

Title	Kaplan-Meier Estimates of Overall Survival
Description	Overall survival was defined as the time in days from the date of first treatment to the date of death due to any cause for all participants. Results are stated in months.
Time Frame	up to 5 years

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Alemtuzumab 30mg
Arm/Group Description	Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Measure Participants	86
Median (95% Confidence Interval) [months]	38.29

5. Secondary Outcome

Title	Participants With a Minimal Residual Disease (MRD) Status of Negative
Description	MRD negativity represents a very positive response outcome. MRD negativity in this report was defined by the absence of tumor cells in bone marrow, using 4-color flow cytometry. All patients are evaluated for treatment response based on National Cancer Institute Working Group (NCIWG) criteria. Of patients who have achieved a clinical complete response (CR) or partial response (PR) that met National Cancer Institute Working Group (NCIWG) criteria of CR except blood recovery, a bone marrow sample was taken for flow cytometry measure of MRD negativity.
Time Frame	44 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Alemtuzumab 30mg
Arm/Group Description	Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Measure Participants	86
Number [participants]	4 4.7%

6. Secondary Outcome

Title	Participants With Treatment-Emergent Adverse Events (TEAE)
Description	Number of participants with treatment-emergent adverse events (TEAEs). AEs were graded by the investigator using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and were assessed for relatedness to study treatment (5 point scale from 'not related' to 'definitely related') and severity (5 point scale with grade 5 being most severe). Categories reported include participant counts for treatment-emergent AEs, injection site reactions, AEs for infections, serious AEs, AEs causing discontinuation of study drug(s), deaths and severity.
Time Frame	up to 18 weeks of treatment plus 45 days

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Alemtuzumab 30mg
Arm/Group Description	Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Measure Participants	86
>=1 TEAE	82 95.3%
>=1 TEAE related to drug	80 93%
>=1 injection site reaction	49 57%
>=1 injection site reaction related to drug	48 55.8%
>=1 infection	49 57%
>=1 infection related to drug	35 40.7%
>=1 serious AE	46 53.5%
>=1 serious AE related to drug	39 45.3%
Discontinued study drug due to AE	21 24.4%
Discontinued study drug due to related AE	20 23.3%
Deaths	12 14%
Deaths within 30 days of last dose	3 3.5%
TEAE with worst severity grade 1	3 3.5%
TEAE with worst severity grade 2	8 9.3%
TEAE with worst severity grade 3	18 20.9%
TEAE with worst severity grade 4	45 52.3%
TEAE with worst severity grade 5	8 9.3%

7. Primary Outcome

Title	Percentage of Participants Who Had an Overall Response (OR) as Determined by the Independent Response Review Panel (IRRP)
Description	Participants were evaluated by the IRRP according to National Cancer Institute (NCI) 1996 response criteria. The percentage of participants whose best response observed during the study was either a Complete Response (CR) or a Partial Response (PR). Overall Response (OR) = CR + PR. A Complete Response (CR) exhibits a normal physical exam, marrow cells and blood values. A Partial Response (PR) has a >= 50% decrease from baseline in lymphocytes, lymphadenopathy and liver or spleen exam.
Time Frame	up to 44 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set. 95% confidence interval calculated using exact binomial method.

Arm/Group Title	Alemtuzumab 30mg
Arm/Group Description	Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Measure Participants	86
Number (95% Confidence Interval) [percentage of participants]	43.0 50%

Adverse Events

Time Frame	Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days
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. Events are listed independent of relationship to treatment reported.
Arm/Group Title	Alemtuzumab 30mg
Arm/Group Description	Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
All Cause Mortality
	Alemtuzumab 30mg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Alemtuzumab 30mg
	Affected / at Risk (%)	# Events
Total	46/86 (53.5%)
Blood and lymphatic system disorders
Bone marrow failure	1/86 (1.2%)
Febrile neutropenia	6/86 (7%)
Idiopathic thrombocytopenic purpura	1/86 (1.2%)
Neutropenia	2/86 (2.3%)
Pancytopenia	4/86 (4.7%)
Thrombocytopenia	2/86 (2.3%)
Cardiac disorders
Angina unstable	1/86 (1.2%)
Atrial fibrillation	1/86 (1.2%)
Left ventricular failure	1/86 (1.2%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	2/86 (2.3%)
Large intestine perforation	1/86 (1.2%)
Peritonitis	1/86 (1.2%)
Rectal haemorrhage	1/86 (1.2%)
General disorders
Asthenia	1/86 (1.2%)
Chills	2/86 (2.3%)
Device dislocation	1/86 (1.2%)
Localised oedema	1/86 (1.2%)
Oedema peripheral	1/86 (1.2%)
Pyrexia	6/86 (7%)
Hepatobiliary disorders
Bile duct obstruction	1/86 (1.2%)
Cholangitis acute	1/86 (1.2%)
Hepatorenal syndrome	1/86 (1.2%)
Immune system disorders
Hypersensitivity	1/86 (1.2%)
Infections and infestations
Abscess neck	1/86 (1.2%)
Aspergillosis	1/86 (1.2%)
Bacteraemia	1/86 (1.2%)
Bronchitis	2/86 (2.3%)
Bronchopneumonia	1/86 (1.2%)
Bronchopulmonary aspergillosis	3/86 (3.5%)
Cellulitis	3/86 (3.5%)
Cytomegalovirus infection	9/86 (10.5%)
Ear infection	1/86 (1.2%)
Escherichia bacteraemia	1/86 (1.2%)
Herpes zoster	1/86 (1.2%)
Infection	1/86 (1.2%)
Lower respiratory tract infection	1/86 (1.2%)
Meningitis	1/86 (1.2%)
Parainfluenzae virus infection	1/86 (1.2%)
Pneumonia	5/86 (5.8%)
Pneumonia fungal	1/86 (1.2%)
Septic shock	2/86 (2.3%)
Upper respiratory tract infection	2/86 (2.3%)
Urinary tract infection	2/86 (2.3%)
Injury, poisoning and procedural complications
Fractured ischium	1/86 (1.2%)
Investigations
Cytomegalovirus test positive	2/86 (2.3%)
Liver function test abnormal	1/86 (1.2%)
Metabolism and nutrition disorders
Decreased appetite	1/86 (1.2%)
Diabetes mellitus	1/86 (1.2%)
Hypercalcaemia	1/86 (1.2%)
Musculoskeletal and connective tissue disorders
Muscular weakness	1/86 (1.2%)
Polymyositis	1/86 (1.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ear neoplasm	1/86 (1.2%)
Richter's syndrome	2/86 (2.3%)
Nervous system disorders
Cerebrovascular accident	1/86 (1.2%)
Encephalitis	1/86 (1.2%)
Headache	2/86 (2.3%)
Hypoglycaemic coma	1/86 (1.2%)
Sciatica	1/86 (1.2%)
Renal and urinary disorders
Nephrolithiasis	1/86 (1.2%)
Renal failure acute	2/86 (2.3%)
Reproductive system and breast disorders
Oedema genital	1/86 (1.2%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/86 (1.2%)
Chronic obstructive pulmonary disease	1/86 (1.2%)
Pleural effusion	1/86 (1.2%)
Pleurisy	1/86 (1.2%)
Skin and subcutaneous tissue disorders
Leukocytoclastic vasculitis	1/86 (1.2%)
Vascular disorders
Orthostatic hypotension	1/86 (1.2%)
Shock haemorrhagic	1/86 (1.2%)
Venous thrombosis limb	1/86 (1.2%)
Other (Not Including Serious) Adverse Events
	Alemtuzumab 30mg
	Affected / at Risk (%)	# Events
Total	81/86 (94.2%)
Blood and lymphatic system disorders
Anaemia	28/86 (32.6%)
Anaemia haemolytic autoimmune	1/86 (1.2%)
Febrile neutropenia	1/86 (1.2%)
Haemolysis	2/86 (2.3%)
Idiopathic thrombocytopenic purpura	1/86 (1.2%)
Leukocytosis	1/86 (1.2%)
Leukopenia	27/86 (31.4%)
Lymphopenia	14/86 (16.3%)
Neutropenia	43/86 (50%)
Thrombocytopenia	17/86 (19.8%)
Cardiac disorders
Angina pectoris	1/86 (1.2%)
Angina unstable	1/86 (1.2%)
Atrial flutter	1/86 (1.2%)
Bradycardia	1/86 (1.2%)
Palpitations	3/86 (3.5%)
Sinus tachycardia	1/86 (1.2%)
Tachycardia	4/86 (4.7%)
Ear and labyrinth disorders
Ear pain	1/86 (1.2%)
Vertigo	3/86 (3.5%)
Endocrine disorders
Hypothyroidism	1/86 (1.2%)
Eye disorders
Conjunctivitis	1/86 (1.2%)
Dry eye	1/86 (1.2%)
Erythema of eyelid	1/86 (1.2%)
Eye haemorrhage	1/86 (1.2%)
Eye irritation	1/86 (1.2%)
Eye pain	1/86 (1.2%)
Lacrimation increased	1/86 (1.2%)
Gastrointestinal disorders
Abdominal distension	2/86 (2.3%)
Abdominal pain	7/86 (8.1%)
Abdominal pain upper	5/86 (5.8%)
Aphthous stomatitis	1/86 (1.2%)
Ascites	1/86 (1.2%)
Constipation	5/86 (5.8%)
Diarrhoea	15/86 (17.4%)
Dry mouth	1/86 (1.2%)
Dyspepsia	2/86 (2.3%)
Epigastric discomfort	1/86 (1.2%)
Flatulence	1/86 (1.2%)
Gastritis	1/86 (1.2%)
Gastrointestinal disorder	1/86 (1.2%)
Gastrointestinal haemorrhage	1/86 (1.2%)
Gastrooesophageal reflux disease	1/86 (1.2%)
Gingival pain	1/86 (1.2%)
Haematochezia	1/86 (1.2%)
Hiatus hernia	1/86 (1.2%)
Ileus	1/86 (1.2%)
Inguinal hernia	1/86 (1.2%)
Melaena	1/86 (1.2%)
Mouth haemorrhage	1/86 (1.2%)
Mouth ulceration	2/86 (2.3%)
Nausea	17/86 (19.8%)
Odynophagia	1/86 (1.2%)
Peptic ulcer	1/86 (1.2%)
Retching	1/86 (1.2%)
Stomatitis	3/86 (3.5%)
Tongue coated	1/86 (1.2%)
Toothache	2/86 (2.3%)
Vomiting	14/86 (16.3%)
General disorders
Asthenia	6/86 (7%)
Axillary pain	1/86 (1.2%)
Catheter site haematoma	1/86 (1.2%)
Chills	20/86 (23.3%)
Fatigue	25/86 (29.1%)
Hypothermia	1/86 (1.2%)
Influenza like illness	1/86 (1.2%)
Injection site erythema	29/86 (33.7%)
Injection site haematoma	1/86 (1.2%)
Injection site pain	2/86 (2.3%)
Injection site pruritus	4/86 (4.7%)
Injection site rash	4/86 (4.7%)
Injection site reaction	14/86 (16.3%)
Injection site swelling	1/86 (1.2%)
Malaise	2/86 (2.3%)
Oedema peripheral	8/86 (9.3%)
Pain	6/86 (7%)
Pyrexia	30/86 (34.9%)
Hepatobiliary disorders
Hepatic function abnormal	1/86 (1.2%)
Hyperbilirubinaemia	2/86 (2.3%)
Immune system disorders
Drug hypersensitivity	1/86 (1.2%)
Hypersensitivity	1/86 (1.2%)
Seasonal allergy	1/86 (1.2%)
Infections and infestations
Acute sinusitis	1/86 (1.2%)
Balanitis candida	1/86 (1.2%)
Bronchitis	2/86 (2.3%)
Cellulitis	1/86 (1.2%)
Clostridial infection	1/86 (1.2%)
Cytomegalovirus infection	6/86 (7%)
Escherichia urinary tract infection	1/86 (1.2%)
Eye infection	1/86 (1.2%)
Folliculitis	1/86 (1.2%)
Influenza	1/86 (1.2%)
Lower respiratory tract infection	2/86 (2.3%)
Nasopharyngitis	7/86 (8.1%)
Oesophageal candidiasis	1/86 (1.2%)
Oral candidiasis	1/86 (1.2%)
Oral fungal infection	1/86 (1.2%)
Oral herpes	1/86 (1.2%)
Oropharyngeal candidiasis	1/86 (1.2%)
Pneumonia	2/86 (2.3%)
Respiratory tract infection	4/86 (4.7%)
Rhinitis	6/86 (7%)
Sinusitis	3/86 (3.5%)
Sinusitis aspergillus	1/86 (1.2%)
Systemic candida	1/86 (1.2%)
Tinea capitis	1/86 (1.2%)
Tinea infection	1/86 (1.2%)
Tracheitis	1/86 (1.2%)
Upper respiratory tract infection	5/86 (5.8%)
Urinary tract infection	4/86 (4.7%)
Injury, poisoning and procedural complications
Arthropod bite	1/86 (1.2%)
Contusion	2/86 (2.3%)
Fall	1/86 (1.2%)
Fibula fracture	1/86 (1.2%)
Post procedural complication	1/86 (1.2%)
Procedural pain	2/86 (2.3%)
Thermal burn	1/86 (1.2%)
Investigations
Alanine aminotransferase increased	1/86 (1.2%)
Aspartate aminotransferase increased	1/86 (1.2%)
Beta 2 microglobulin increased	1/86 (1.2%)
Blood alkaline phosphatase increased	2/86 (2.3%)
Blood bilirubin increased	1/86 (1.2%)
Blood creatinine increased	2/86 (2.3%)
Blood iron decreased	1/86 (1.2%)
Blood potassium decreased	2/86 (2.3%)
Blood pressure increased	1/86 (1.2%)
Blood urea increased	1/86 (1.2%)
Body temperature increased	1/86 (1.2%)
CD4 lymphocytes decreased	1/86 (1.2%)
Cytomegalovirus test positive	13/86 (15.1%)
Eosinophil count increased	1/86 (1.2%)
Gamma-glutamyltransferase increased	1/86 (1.2%)
International normalised ratio increased	1/86 (1.2%)
Neutrophil count decreased	1/86 (1.2%)
Protein total decreased	2/86 (2.3%)
Serum ferritin increased	1/86 (1.2%)
Weight decreased	8/86 (9.3%)
White blood cell count decreased	1/86 (1.2%)
Metabolism and nutrition disorders
Decreased appetite	12/86 (14%)
Fluid retention	2/86 (2.3%)
Hyperglycaemia	2/86 (2.3%)
Hyperkalaemia	1/86 (1.2%)
Hyperuricaemia	1/86 (1.2%)
Hypoalbuminaemia	2/86 (2.3%)
Hypocalcaemia	1/86 (1.2%)
Hypokalaemia	3/86 (3.5%)
Hyponatraemia	3/86 (3.5%)
Increased appetite	1/86 (1.2%)
Malnutrition	1/86 (1.2%)
Pseudohyperkalaemia	1/86 (1.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/86 (4.7%)
Back pain	5/86 (5.8%)
Bone pain	1/86 (1.2%)
Joint effusion	1/86 (1.2%)
Joint swelling	2/86 (2.3%)
Muscle spasms	4/86 (4.7%)
Muscular weakness	2/86 (2.3%)
Musculoskeletal chest pain	3/86 (3.5%)
Musculoskeletal discomfort	1/86 (1.2%)
Musculoskeletal pain	1/86 (1.2%)
Musculoskeletal stiffness	1/86 (1.2%)
Myalgia	2/86 (2.3%)
Pain in extremity	4/86 (4.7%)
Polymyositis	1/86 (1.2%)
Spondylitis	1/86 (1.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroma	1/86 (1.2%)
Melanocytic naevus	1/86 (1.2%)
Nervous system disorders
Ageusia	1/86 (1.2%)
Dizziness	7/86 (8.1%)
Dysarthria	1/86 (1.2%)
Dyskinesia	1/86 (1.2%)
Headache	16/86 (18.6%)
Hemiparesis	1/86 (1.2%)
Hypoaesthesia	1/86 (1.2%)
Lethargy	4/86 (4.7%)
Migraine	1/86 (1.2%)
Neuralgia	1/86 (1.2%)
Paraesthesia	5/86 (5.8%)
Peripheral sensory neuropathy	2/86 (2.3%)
Sciatica	1/86 (1.2%)
Somnolence	1/86 (1.2%)
Syncope	1/86 (1.2%)
Tremor	3/86 (3.5%)
Psychiatric disorders
Agitation	2/86 (2.3%)
Anxiety	4/86 (4.7%)
Confusional state	2/86 (2.3%)
Depression	2/86 (2.3%)
Insomnia	9/86 (10.5%)
Mood altered	1/86 (1.2%)
Neurosis	1/86 (1.2%)
Stress	1/86 (1.2%)
Renal and urinary disorders
Dysuria	2/86 (2.3%)
Haematuria	1/86 (1.2%)
Nocturia	1/86 (1.2%)
Pollakiuria	2/86 (2.3%)
Renal failure	2/86 (2.3%)
Reproductive system and breast disorders
Balanitis	1/86 (1.2%)
Breast oedema	1/86 (1.2%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/86 (1.2%)
Cough	14/86 (16.3%)
Dysphonia	2/86 (2.3%)
Dyspnoea	14/86 (16.3%)
Dyspnoea exertional	2/86 (2.3%)
Epistaxis	1/86 (1.2%)
Haemoptysis	1/86 (1.2%)
Hypoxia	2/86 (2.3%)
Oropharyngeal pain	3/86 (3.5%)
Orthopnoea	1/86 (1.2%)
Pleural effusion	1/86 (1.2%)
Pleurisy	1/86 (1.2%)
Productive cough	2/86 (2.3%)
Pulmonary hypertension	1/86 (1.2%)
Respiratory disorder	1/86 (1.2%)
Respiratory failure	1/86 (1.2%)
Respiratory tract congestion	1/86 (1.2%)
Rhinorrhoea	1/86 (1.2%)
Sinusitis noninfective	1/86 (1.2%)
Tachypnoea	1/86 (1.2%)
Throat tightness	1/86 (1.2%)
Tonsillar disorder	1/86 (1.2%)
Vasomotor rhinitis	1/86 (1.2%)
Skin and subcutaneous tissue disorders
Blister	1/86 (1.2%)
Dermatitis allergic	1/86 (1.2%)
Dry skin	3/86 (3.5%)
Ecchymosis	1/86 (1.2%)
Eczema	1/86 (1.2%)
Erythema	9/86 (10.5%)
Hyperhidrosis	3/86 (3.5%)
Night sweats	12/86 (14%)
Petechiae	3/86 (3.5%)
Pityriasis rosea	1/86 (1.2%)
Pruritus	11/86 (12.8%)
Pruritus generalised	1/86 (1.2%)
Rash	8/86 (9.3%)
Rash generalised	1/86 (1.2%)
Rash maculo-papular	1/86 (1.2%)
Skin reaction	2/86 (2.3%)
Urticaria	3/86 (3.5%)
Vascular disorders
Haematoma	1/86 (1.2%)
Hypertension	4/86 (4.7%)
Hypotension	6/86 (7%)
Orthostatic hypotension	3/86 (3.5%)
Phlebitis	1/86 (1.2%)

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 an independent multi-investigator publication (in which the PI can participate) 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.