A Safety Confirmatory Study of Alemtuzumab in Japanese Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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The primary objective of this study is to confirm the safety profile of alemtuzumab 30 mg (the US/European Union (EU) approved dose) in Japanese patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL).

Detailed Description
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NOTE: This study was previously posted by Bayer. In December 2009, this study was acquired by Genzyme Corporation. Genzyme Japan K.K. is the sponsor of the trial.

Official Title
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A Japanese Phase I Study of Alemtuzumab in Japanese Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

Conditions
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Leukemia, Lymphocytic, Chronic, B-Cell

Intervention / Treatment
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* Drug: alemtuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: B-cell Chronic Lymphocytic Leukemia (B-CLL) according to the 1996 National Cancer Institute-sponsored Working Group (NCI-WG) Criteria One or more, but <= 3 previous treatment regimens for Chronic Lymphocytic Leukemia (CLL) Patient requires treatment for CLL (Rai stage III and IV disease or stage 0 to II disease with evidence of progression) Adequate bone marrow, liver and renal function More than 4 weeks since prior chemotherapy or chemoimmunotherapy, including investigational agents, for the treatment of CLL. Patient must have recovered from the acute side effects incurred as a result of previous therapy World Health Organization (WHO) Performance Status (PS) 0,1 Life expectancy of at least 24 weeks Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and 2 weeks after the completion of trial Written informed consent Exclusion Criteria: Known human immunodeficiency virus (HIV) seropositivity 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]) Active uncontrolled infection Recent documented history (within 2 years) of active tuberculosis (TB), current active TB infection, currently receiving anti-tuberculous medication (e.g., isoniazid, rifampin, streptomycin, pyrazinamide, or others) Positive cytomegalovirus (CMV) by Polymerase Chain Reaction (PCR) assay Transformation to aggressive lymphoma (e.g., Richter's syndrome) Past history of anaphylaxis following exposure to humanized monoclonal antibodies Previous treatment with alemtuzumab Previous hematopoietic stem cell transplant Pregnant or breast-feeding patients Central nervous system (CNS) involvement with CLL Other severe, concurrent diseases (e.g., cardiac or pulmonary disease), mental disorders, or major organ malfunction (e.g., liver, kidney) that could interfere with the patient's ability to participate in the study Medical condition requiring chronic use of oral corticosteroids at a dose higher than physiologic replacement. Active malignancy, other than CLL, which needs therapy with anti-cancer drug(s) Autoimmune anemia and/or thrombocytopenia Small lymphocytic lymphoma

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alemtuzumab<br>The starting dose of alemtuzumab was 3 mg. The dose was gradually escalated on a daily basis (3 mg, 10 mg, and then 30 mg) until the patient tolerated a dose of 30 mg IV infusion over 2 hours. All subsequent doses of alemtuzumab were 30 mg IV 3 times a week (every other day). | Drug: alemtuzumab<br> <br> * Other names: MabCampath, BAY86-5045, CAMPATH-1H;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety profile: As measured by physical examinations, vital signs, adverse events, concomitant medications and laboratory tests |  | Until 24 weeks after end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate: Defined as the proportion of patients who achieved complete remission (CR) or partial remission (PR) as the best response according to the investigator's determination using the NCIWG response criteria |  | Until 24 weeks after end of treatment | 
| Pharmacokinetic profiles: Area under the serum concentration vs time curve over the dosing interval, Maximum drug concentration in serum, terminal elimination half-life following the last dose, total body clearance and volume of distribution |  | until 24 weeks after end of treatment | 
| Time to response: Defined as the time from date of initial treatment until first objective documentation of response (CR or PR) as determined by the investigator. | If a patient achieves PR before CR, the onset date of PR will be used in the calculation | Until 24 weeks after end of treatment | 
| Duration of response: Defined as the time from first objective documentation of response (CR or PR) by the investigator to first objective documentation of progressive disease by the investigator |  | Until 24 weeks after end of treatment | 
| Time to progression: Defined as the time from date of initial treatment to first objective documentation of progressive disease by the investigator |  | Until 24 weeks after end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLL, Relapsed or Refractory Chronic Lymphocytic Leukemia,