A Phase II, Open Label, Single Arm, Multicenter Study of Chlorambucil in Japanese Previously Untreated Patients With Chronic Lymphocytic Leukemia

NCT01808326 | Completed Phase 2 Results

• 1 other identifier: 116586
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 6

Brief Summary

This study is an open-label, single arm, phase II study of chlorambucil in subjects with previously untreated CLL. The primary objective is to evaluate the response to chlorambucil in Japanese subjects with previously untreated CLL. Secondary objectives are to evaluate efficacy, safety and pharmacokinetics of chlorambucil in Japanese subjects.

Conditions

Leukaemia, Lymphoblastic

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Best Response of Either Complete Remission (CR), Nodular Partial Remission (nPR), Complete Remission-incomplete (CRi) or Partial Remission (PR), as Assessed by the Investigator, IRC and IRC With CT

  According to the criteria based on the 2008 revision of the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) of the National Cancer Institute-Sponsored Working Group Guidelines (NCI-WG), participants with complete remission (CR), nodular partial remission (nPR), complete remission-incomplete (CRi) and partial remission (PR) were classified as responders, while stable disease (SD) and progressive disease (PD) were classified as non-responders. Participants with unknown or missing responses were considered as non-responders. Assessment was completed by the Investigator, Independent Review Committee (IRC), and IRC with Computed Tomography (CT).

  From the start of treatment until disease progression or death (up to Week 61.1)

Secondary Outcomes (23)

• Number of Participants With the Best Overall Response (OR), as Assessed by the Investigator, IRC and IRC With CT

  From the start of treatment until disease progression or death (up to Week 61.1)

• Progression Free Survival (PFS), as Assessed by the Investigator and the IRC

  From the start of treatment until disease progression or death (up to Week 61.1)

• Overall Survival (OS)

  From the start of treatment until death (up to Week 61.1)

• Time to Response, as Assessed by the IRC

  From the start of treatment until the first response (CR/PR) (up to Week 61.1)

• Duration of Response, as Assessed by the IRC

  From the initial response (CR/PR) until disease progression or death (up to Week 61.1)

Study Arms (1)

chlorambucil

EXPERIMENTAL

chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 treatment cycles

Drug: chlorambucil, tablets

Interventions

chlorambucil, tablets DRUG

2mg tablets, chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 cycles

chlorambucil

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of CLL defined by:Circulating B lymphocytes ≥5,000 /μL AND Flow cytometry confirmation of immunophenotype with CD5, CD19, CD20, and CD23 prior to Visit 2.
• Considered inappropriate for fludarabine-based therapy.
• Active disease and indication for treatment based on the IWCLL updated NCI-WG guidelines defined by presenting at least any one of the following conditions: Evidence of progressive marrow failure as manifested by development or worsening of anemia and/or thrombocytopenia.
• Massive (i.e. at least 6 cm below the left costal margin) or progressive or symptomatic splenomegaly.
• Massive nodes (i.e. at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.
• Progressive lymphocytosis with an increase of more than 50% over a two month period or an lymphocyte doubling time of less than 6 months.
• A minimum of any one of the following disease-related symptoms must be present: a) Unintentional weight loss ≥10% within the previous six months; b) Fevers \>38.0°C for ≥ 2 weeks without evidence of infection; or c) Night sweats for more than 1 month without evidence of infection
• Not been previously treated for CLL (prior autoimmune hemolytic anemia treatment with corticosteroids permitted).
• ECOG Performance Status of 0-2.
• The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period.
• Life expectancy of at least 6 months, in the opinion of the investigator.
• Age ≥ 20 years
• Signed written informed consent prior to performing any study-specific procedures (the results of other procedures predating the informed consent can be used).

You may not qualify if:

• Prior immuno- or chemotherapy for CLL or small lymphocytic lymphoma (SLL) with any agent except corticosteroids used to treat autoimmune hemolytic anemia.
• Previous autologous or allogeneic stem cell transplantation.
• Active autoimmune hemolytic anemia (AIHA) requiring corticosteroid therapy \>100 mg/day equivalent to hydrocortisone, or chemotherapy.
• Known transformation of CLL (e.g. Richter).
• Known CNS involvement of CLL.
• Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C.
• Other past or current malignancy. Subjects who have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible.
• Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to screening, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities.
• History of significant cerebrovascular disease or event with significant symptoms or sequelae.
• Glucocorticoid use, unless given in doses ≤ 100 mg/day hydrocortisone (or equivalent dose of other glucocorticoid) for \<7 days for exacerbations other than CLL (e.g. asthma).
• Known HIV positive.
• Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb and/or HBsAb positive, an HBV DNA test will be performed, and if positive the subject will be excluded.
• Screening laboratory values:
• Creatinine \>2.0 times upper normal limit (unless normal creatinine clearance). Total bilirubin \> 2.0 times upper normal limit (unless due to Gilbert's syndrome).
• Alanine aminotransferase (ALT) \> 3.0 times upper normal limit.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (6)

GSK Investigational Site

Aichi, 466-8650, Japan

Location

GSK Investigational Site

Fukuoka, 811-1395, Japan

Location

GSK Investigational Site

Gunma, 373-8550, Japan

Location

GSK Investigational Site

Miyagi, 980-8574, Japan

Location

GSK Investigational Site

Tokyo, 104-0045, Japan

Location

GSK Investigational Site

Tokyo, 135-8550, Japan

Location

MeSH Terms

Conditions

Leukemia

Interventions

Chlorambucil; Tablets

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2013
• First Posted: March 11, 2013
• Study Start: April 1, 2013
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: June 22, 2015
• Results First Posted: June 22, 2015

Record last verified: 2015-04

Locations

JP (6)