A Phase I/II, Open-label Study of Ofatumumab Added to Chlorambucil in Previously Untreated Japanese Patients With Chronic Lymphocytic Leukemia

NCT01563055 | Completed Phase 2 Results

• 1 other identifier: 115601
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 6

Brief Summary

This is an open-label study to evaluate tolerability, safety, efficacy and pharmacokinetic profile of ofatumumab in combination with chlorambucil in Japanese patients with previously untreated Chronic Lymphocytic Leukemia (CLL).

Conditions

Leukaemia, Lymphocytic, Chronic

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Developed Toxicity Requiring Discontinuation From Study Treatment During Cycle 1

  Tolerability of ofatumumab in combination with chlorambucil was evaluated based on the number of participants who developed toxicity requiring discontinuation from study treatment during Cycle 1. The treatment was considered tolerable when 0 of 3 participants, or \<=2 of 6 participants developed toxicity which required discontinuation of study treatment during Cycle 1. The toxicity requiring discontinuation was determined based on the pre-defined withdrawal criteria.

  From start of treatment through Cycle 1 (Week 4)

• Number of Participants With Overall Response, as Assessed by the Independent Review Committee (IRC) With CT, IRC and Investigator

  Response evaluated as per International Workshop for Chronic Lymphocytic Leukemia (IWCLL) National Cancer Institute-sponsored Working Group (NCI-WG) Guidelines, 2008. Overall response rate (ORR) is defined as percentage of par. achieving complete remission (CR), nodular partial remission (nPR), CR-incomplete (CRi) or PR. CR (\>=2 months after last treatment): lymphocytes (LC) \<4000 per microliter (μL), no lymphadenopathy (Ly)\>1.5 cm/hepatomegaly/splenomegaly/constitutional symptoms; neutrophils (N)\>1500/µL, platelets (PL)\>100,000/µL, hemoglobin (Hb)\>11 grams/deciliter (g/dL), bone marrow (BM) sample must be normocellular for age,\<30% LC, no lymphoid nodule (LN). PR:\>=50% decrease in LC, Ly, size of liver and spleen; and at least one of these: N\>1500/μL, PL\>100,000/µL or 50% improvement over Baseline (BL), Hb\>11 g/dL or 50% improvement over BL. nPR: persistent nodules BM. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity.

  From start of treatment until disease progression or death (up to Week 62.3)

Secondary Outcomes (53)

• Number of Participants With CR, as Assessed by the IRC, IRC With CT, and the Investigator

  From start of treatment until disease progression or death (up to Week 62.3)

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

  From start of treatment until disease progression or death (up to Week 62.3)

• Overall Survival

  From start of treatment until death (up to Week 62.3

• Time to Response, as Assessed by the IRC

  From start of treatment until the first response (CR/CRi/nPR/PR) (up to Week 62.3)

• Duration of Response, as Assessed by the IRC

  From initial response (CR/CRi/nPR/PR) until disease progression or death (up to Week 62.3)

Study Arms (1)

ofatumumab + chlorambucil

EXPERIMENTAL

ofatumumab dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days; 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; Drug: ofatumumab (GSK1841157) infusion

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

ofatumumab + chlorambucil

ofatumumab (GSK1841157) infusion DRUG

iv infusion; dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days;

ofatumumab + 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 modified 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 degree 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 permitted).
• ECOG Performance Status of 0-2.
• 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.
• Patients possible to stay at the trial site for at least two days (the day of the first infusion and a subsequent day).

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 (Visit 1), 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 transaminase (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

Hokkaido, 060-8543, Japan

Location

GSK Investigational Site

Kanagawa, 259-1143, Japan

Location

GSK Investigational Site

Kyoto, 602-8566, Japan

Location

GSK Investigational Site

Tokyo, 104-0045, Japan

Location

GSK Investigational Site

Tokyo, 135-8550, Japan

Location

MeSH Terms

Conditions

Leukemia, B-Cell

Interventions

Chlorambucil; Tablets; ofatumumab

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System 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: March 15, 2012
• First Posted: March 26, 2012
• Study Start: April 1, 2012
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: August 10, 2015
• Results First Posted: August 10, 2015

Record last verified: 2015-07

Locations

JP (6)