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

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

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).

Study Overview

• Status: Completed
• Conditions: Leukemia, Lymphocytic, Chronic, B-Cell
• Intervention / Treatment: Drug: alemtuzumab

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan, 260-8677
  • Aichi
    • Nagoya, Aichi, Japan, 466-8650
  • Ibaraki
    • Tsukuba, Ibaraki, Japan, 305-8576
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8519
    • Chuo-ku, Tokyo, Japan, 104-0045

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alemtuzumab; 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; Other Names: MabCampath, BAY86-5045, CAMPATH-1H

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: June 9, 2009
• First Submitted That Met QC Criteria: June 17, 2009
• First Posted (Estimate): June 18, 2009

Study Record Updates

• Last Update Posted (Estimate): April 30, 2015
• Last Update Submitted That Met QC Criteria: April 29, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: CLL; Relapsed or Refractory Chronic Lymphocytic Leukemia,
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Antineoplastic Agents; Antineoplastic Agents, Immunological; Alemtuzumab
• Other Study ID Numbers: CAMCLL07709; 14020