A Phase I/II, a Single Arm, Open-label Study of Ofatumumab (GSK1841157) in Patients With Previously Treated Chronic Lymphocytic Leukemia

NCT01077622 | Completed Phase 2 Results

• 1 other identifier: 112758
• Study Type: interventional
• Target: 10
• Locations: 2 countries
• Sites: 7

Brief Summary

Ofatumumab is an IgG1κ fully human monoclonal antibody (mAb) that specifically recognizes an epitope on the human differentiation antigen CD20 molecule. In vitro and in vivo studies demonstrated that ofatumumab depletes CD20 positive (CD20+) B cells through complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC), which results in the antitumour effect. This is an open-label study to evaluate safety, tolerability, efficacy and PK profile of ofatumumab monotherapy in chronic lymphocytic leukemia (CLL) patients. Ofatumumab will be administered intravenously at the first dose of 300mg followed by 7 weekly infusions of 2000mg, followed by 4 infusions of 2000mg at every 4 weeks. Primary objective of the study (Part A) is to evaluate tolerability, and the study (Part B) is to assess overall response rate in CLL population. 10 subjects will be enrolled into this study. Subjects will be followed for 48 weeks.

Conditions

Leukaemia, Lymphocytic, Chronic

Outcome Measures

Primary Outcomes (2)

• Number of Participants With a Dose-limiting Toxicity (DLT)

  A DLT was defined as the following toxicological findings, according to the Common Terminology Criteria for Adverse Events (AE) v3.0: any treatment-related Grade (G) \>=3 non-hematotoxic AE, occurrence of G3 infusion reaction (treatment-related AE) at the day of infusion in a participant who received pre-medication or appropriate management during infusion (glucocorticoid) (the severity of the AE must have remained as \>= G3 until the next day); and any of following: \>= G4 hematotoxic treatment-related AEs (neutropenia lasting 7 days or more, febrile neutropenia).

  Up to Week 8

• Percentage of Participants (Par.) With Objective Response (OR), Defined as Complete Remission (CR), CR Incomplete (CRi), Partial Remission (PR), and Nodular PR (nPR) as Assessed by a Safety and Evaluation Review Committee (SERC) and the Investigator

  Par. were evaluated in accordance with the National Cancer Institute-sponsored Working Group. CR: no lymphadenopathy (Ly)/hepatomegaly/splenomegaly/constitutional symptoms; neutrophils \>=1.5\*10\^9/liter (L), platelets \>100\*10\^9/L, hemoglobin \>11.0 grams/deciliter, lymphocytes (LC) \<4.0\*10\^9/L, bone marrow (BM) sample must be normocellular for age, \<30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to chronic lymphocytic leukemia but related to drug toxicity. PR: \>=50% decrease in LC, Ly, size of liver and spleen, etc. nPR: nodules in BM.

  Up to Week 48

Secondary Outcomes (40)

• Progression-free Survival (PFS) as Assessed by a SERC

  Up to Week 48

• Duration of Response as Assessed by a SERC

  Up to Week 48

• Overall Survival

  Up to Week 48

• Time to Response as Assessed by a SERC

  Up to Week 48

• Time to Next Chronic Lymphocytic Leukemia (CLL) Therapy as Assessed by a SERC

  Up to Week 48

Other Outcomes (1)

• Serum Hemolytic Complement Titer at Weeks 36 and 48: CH50

  Weeks 36 and 48

Study Arms (1)

2000 mg dose

EXPERIMENTAL

ofatumumab , 300mg followed by 7 weekly infusions 2000 mg, followed by 4 monthly infusions 2000mg

Drug: ofatumumab 100 mg, 1000 mg / vial

Interventions

ofatumumab 100 mg, 1000 mg / vial DRUG

ofatumumab , 300mg followed by 7 weekly infusions 2000 mg, followed by 4 monthly infusions 2000mg

2000 mg dose

Eligibility Criteria

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

You may qualify if:

• Subjects eligible for enrolment in the study must meet all of the following criteria at the time of screening:
• Patients who gave consent to this study participation and signed into informed consent form.
• Previously treated(Patients who received at least one prior CLL therapy and have either relapsed or have refractory disease, both requiring therapy.) CLL with at least 5 x 109 B lymphocytes/ L (5000/μL). The diagnosis of CLL requires CD5, CD19, CD20 and CD23 positivity, according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines \[Hallek, 2008\].
• Laboratory test values meet the following criteria which indicate that patients have sufficient physiological functions;
• Neutrophils:1≥ 500 /mm3 ALT ≤ 2.5 times upper local normal limit Creatinine ≤ 1.5 times upper local normal limit Total bilirubin≤ 1.5 times upper local normal limit
• :Patients should not receive any hematopoietic cytokine such as G-CSF preparations within 1 week before screening laboratory test for neutrophil counting.
• \- Patients who passed the following periods from the last anti-cancer treatments at the time of screening: At least 4 weeks after anti-cancer chemotherapy. At least 4 weeks after anti-cancer radiotherapy. At least 4 weeks after glucocorticoids treatment for CLL unless ≤ 10 mg of prednisolone /day.
• At least 12 weeks after radio-immunotherapy and/or antibody therapy.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2.
• Life expectancy more than 24 weeks after screening test.
• Aged ≥ 20 (at the time of signing informed consent).
• 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:

• Active malignancy which needs therapy with anti-cancer drug, except for CLL.
• Known Richter's transformation.
• Previous autologous stem cell transplantation, within 24 weeks prior to screening.
• Previous allogenic stem cell transplantation.
• Known CNS involvement.
• History of significant cerebrovascular disease.
• Current cardiac disease requiring medical treatment (e.g. atrial flutter treated with acetylsalicylic acid and beta blocking agents).
• Chronic or active infectious disease requiring systemic (intravenous or oral) treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis and tuberculosis.
• Suspected/known immediate or delayed hypersensitivity to components of ofatumumab.
• Patients previously treated with ofatumumab.
• Positive serology test for any of HBsAg, anti-HBcAb or anti-HCVAb. If only anti-HBcAb results is positive, HBV-DNA test will be performed. If HBV-DNA results in negative, the patient is eligible.
• HIV positivity.
• Pregnant or lactating women.
• Women of childbearing potential not willing to use adequate contraception during the study and one year after the last dose of ofatumumab, and male patients not willing to use adequate contraception during the study. Adequate contraception is defined as follows but not limited to; Abstinence. Oral Contraceptive (exclude oral progesterone alone). Intrauterine device (IUD) or intrauterine system (IUS). Male partner sterilization. Double barrier method: condom or occlusive cap (diaphragm or cervical / vault caps) plus spermicidal agent (gel / film) etc.
• Use of an investigational drug within 4 weeks prior to screening.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (7)

GSK Investigational Site

Aichi, 466-8650, Japan

Location

GSK Investigational Site

Kanagawa, 259-1143, Japan

Location

GSK Investigational Site

Nagasaki, 852-8501, Japan

Location

GSK Investigational Site

Tokyo, 104-0045, Japan

Location

GSK Investigational Site

Tokyo, 135-8550, Japan

Location

GSK Investigational Site

Seoul, 110-744, South Korea

Location

GSK Investigational Site

Seoul, 138-736, South Korea

Location

MeSH Terms

Conditions

Leukemia, B-Cell

Interventions

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

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 25, 2010
• First Posted: March 1, 2010
• Study Start: September 1, 2009
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: May 30, 2017
• Results First Posted: January 27, 2012

Record last verified: 2013-10

Locations

JP (5); KR (2)