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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01563055
First received: March 15, 2012
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

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).


Condition Intervention Phase
Leukaemia, Lymphocytic, Chronic
Drug: chlorambucil, tablets
Drug: ofatumumab (GSK1841157) infusion
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II, Open-label Study of Ofatumumab Added to Chlorambucil in Previously Untreated Japanese Patients With Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Tolerability [ Time Frame: Up to Week 4 ] [ Designated as safety issue: No ]
    Number of subjects who develop toxicity requiring discontinuation from study treatment during Cycle 1

  • Overall response rate (ORR) [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete remission (CR) rate [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  • Progression free survival (PFS) [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  • Time to response and Duration of response [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  • Time to next therapy [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  • Improvement of ECOG performance status [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  • Improvement in B-symptoms/constitutional symptoms/fatigue [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  • Incidence and severity of AEs and SAEs [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  • Incidence of autoimmune hemolytic anemia (AIHA) [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  • Development of Human anti-human antibody (HAHA) [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  • Incidences of and patients with grade 3 and 4 infections and myelosuppression (anemia, neutropenia, thrombocytopenia) [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  • Change in IgG, IgA, IgM quantities [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  • Minimal Residual Disease (MRD) [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  • Change in B-cell counts (CD5+CD19+ and CD5+CD19-) [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  • Prognostic and biological markers correlating with clinical response including β2 microglobulin and Complement CH50 [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  • Pharmacokinetics of ofatumumab and chlorambucil [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
    PK blood samples of ofatumumab will be collected at Day 1, 8 and 15 in Cycle 1, Day1 and 15 in Cycle 2, Day 1 and 15 in Cycle 3, Day1 in Cycle 4, Day 1 in Cycle 5, 6, 9 and 12, and Day 1, 85 and 169 in follow-up period. PK blood samples of chlorambucil will be collected at Day 1 and 4 in Cycle 1, and at Day 1 in Cycle 3.


Estimated Enrollment: 10
Study Start Date: April 2012
Estimated Study Completion Date: November 2014
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ofatumumab + chlorambucil
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
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
Drug: ofatumumab (GSK1841157) infusion
iv infusion; dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days;

Detailed Description:

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). Ofatumumab will be infused intravenously at Day 1 (300 mg) and Day 8 (1000 mg) in the first 28-day cycle, followed by infusions of 1000 mg at the first day of each 28-day cycle. Chlorambucil will be given 10 mg/m2 at Day 1-7 in each 28-day cycle.

The primary objectives are to evaluate tolerability and overall response rate (ORR) of ofatumumab with chlorambucil for previously untreated (frontline) CLL.

Secondary objectives include to evaluate complete remission (CR) rate, progression free survival (PFS), overall survival (OS), time to response, duration of response, time to next therapy, incidence and severity of adverse events and serious adverse events, incidences of grade 3 and 4 infections and myelosuppression (anemia, neutropenia, thrombocytopenia), and pharmacokinetics of ofatumumab and chlorambucil.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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.

  • Previous treatment or known or suspected hypersensitivity to ofatumumab that in the opinion of the investigator or medical monitor is a contraindication to their participation in the present study.
  • Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to Visit 1, whichever is longer, treatment with any anti-CD20 monoclonal antibody within 3 months of Visit 1, or participation in any other interventional clinical study. Note: Participation in any other interventional clinical study after disease progression during post PD-follow-up is permitted.
  • Known or suspected inability to comply with study protocol.
  • Lactating women, women with a positive pregnancy test at Visit 1 or women (of childbearing potential) as well as men with partners of childbearing potential, who are not willing to use adequate contraception from study start through one year following last treatment dose. Adequate contraception is defined as oral hormonal birth control, intrauterine device, male partner sterilization (if male partner is sole partner for that subject) and the double barrier method (condom or occlusive cap plus spermicidal agent).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01563055

Locations
Japan
GSK Investigational Site
Aichi, Japan, 466-8650
GSK Investigational Site
Hokkaido, Japan, 060-8543
GSK Investigational Site
Kanagawa, Japan, 259-1143
GSK Investigational Site
Kyoto, Japan, 602-8566
GSK Investigational Site
Tokyo, Japan, 135-8550
GSK Investigational Site
Tokyo, Japan, 104-0045
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01563055     History of Changes
Other Study ID Numbers: 115601
Study First Received: March 15, 2012
Last Updated: July 7, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Chlorambucil
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014