Clinical trial NCT00923182: A Safety Confirmatory Study of Alemtuzumab in Japanese Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
Official title: A Japanese Phase I Study of Alemtuzumab in Japanese Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia, Lymphocytic, Chronic, B-Cell
Keywords: Relapsed or Refractory Chronic Lymphocytic Leukemia,
CLL
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2009-06-18
Enrollment: 6
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety profile: As measured by physical examinations, vital signs, adverse events, concomitant medications and laboratory tests
timeFrame: Until 24 weeks after end of treatment
Secondary outcomes:
measure: 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
timeFrame: Until 24 weeks after end of treatment
measure: 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
timeFrame: until 24 weeks after end of treatment
measure: 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.
timeFrame: Until 24 weeks after end of treatment
measure: 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
timeFrame: Until 24 weeks after end of treatment
measure: Time to progression: Defined as the time from date of initial treatment to first objective documentation of progressive disease by the investigator
timeFrame: Until 24 weeks after end of treatment
Other outcomes:
Locations:
city: Nagoya
country: Japan
state: Aichi
city: Tsukuba
country: Japan
state: Ibaraki
city: Sendai
country: Japan
state: Miyagi
city: Bunkyo-ku
country: Japan
state: Tokyo
city: Chuo-ku
country: Japan
state: Tokyo
city: Chiba
country: Japan
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Ishizawa K, Fukuhara N, Nakaseko C, Chiba S, Ogura M, Okamoto A, Sunaga Y, Tobinai K. Safety, efficacy and pharmacokinetics of humanized anti-CD52 monoclonal antibody alemtuzumab in Japanese patients with relapsed or refractory B-cell chronic lymphocytic leukemia. Jpn J Clin Oncol. 2017 Jan;47(1):54-60. doi: 10.1093/jjco/hyw146. Epub 2016 Oct 7.