Ofatumumab for Patients With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT01113632
First received: April 28, 2010
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

The risk of immunosuppression deters many patients from receiving fludarabine, while combination chemotherapy regimens are poorly tolerated by elderly or infirm chronic lymphocytic leukemia (CLL) patients. Previous studies by our group and others have shown that rituximab is safe and well tolerated when used as a single agent in patients with CLL. In addition, maintenance therapy with rituximab was well tolerated by CLL patients, with probable prolongation of progression-free survival (Hainsworth et al. 2003). Based on pre clinical and clinical studies indicating possible increased efficacy of ofatumumab in patients with CLL, we wish to develop an antibody-only regimen for older patients and patients who refuse fludarabine-based regimens.


Condition Intervention Phase
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Drug: Ofatumumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Ofatumumab for Older Patients and Patients Who Refuse Fludarabine-Based Regimens With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    To assess the overall response rate of patients with previously untreated CLL or SLL receiving ofatumumab.


Secondary Outcome Measures:
  • To assess the response and PFS [ Time Frame: 18 months ] [ Designated as safety issue: No ]

    To assess the following in patients with previously untreated CLL or SLL receiving ofatumumab:

    • Number of complete responses
    • Number of partial responses
    • Progression-free survival
    • Safety of the treatment regimen
    • Correlation of response based upon pre-treatment biologic features of CLL/SLL cells and innate immune effector cells


Enrollment: 77
Study Start Date: July 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ofatumumab 1000mg
Ofatumumab 300mg IV Day 1 followed by ofatumumab 1000mg weekly for a total of 8 weeks
Drug: Ofatumumab
IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 2000 mg.
Experimental: Ofatumumab 2000mg
Ofatumumab 300mg IV Day 1 followed by ofatumumab 2000mg weekly for a total of 8 weeks
Drug: Ofatumumab
IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 2000 mg.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. CD20+ B-cell chronic lymphocytic leukemia (B-CLL) or small lymphocytic lymphoma according to NCI criteria (see Appendix B).
  2. Previously untreated CLL or small lymphocytic lymphoma (SLL).
  3. Patients must require treatment according to NCI-Working Group guidelines (see Appendix C).
  4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤2 (see Appendix A).
  5. Laboratory values as follows ≤7 days of initiation of treatment:

    • Creatinine <3.0 mg/dL
    • Aspartate amino transferase (AST) or alanine amino transferase (ALT) and alkaline phosphatase (ALP) must be <3 x upper limit of normal (ULN)
    • Total bilirubin <1.5 x the institutional ULN
  6. Patients must be hepatitis B sAg negative. Note: Patients who are HepB sAg negative but are HepB cAb positive (regardless of HepB sAb status) will NOT be allowed.
  7. Women of childbearing potential must have a negative serum pregnancy test performed ≤7 days prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.
  8. Patients ≤ 65 years of age, or patients 18-64 years of age who have declined fludarabine-based regimens, are eligible.
  9. Patient must be accessible for treatment and follow-up.
  10. Patients must be able to understand the nature of this study, give written informed consent prior to study entry, and comply with study requirements.

Exclusion Criteria:

  1. Previous therapy for CLL/SLL. (Patients who have received steroids or IVIG for autoimmune complications of CLL are eligible).
  2. Current active hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease, per assessment by the treating physician).
  3. Active bacterial or viral infection, or infection requiring intravenous antibiotic treatment at the time of accrual.
  4. Central nervous system lymphoma/CLL.
  5. Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (i.e., Richters transformation).
  6. History of other malignancy within 2 years of study entry which could affect compliance with the protocol or interpretation of results. Patients with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix, low grade, early-stage, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ (DCIS) of the breast treated with curative intent, are generally eligible. These cases should be discussed with the study chair or study co-chair prior to enrollment.
  7. Patients who are HepB sAg positive and/or HepB cAb positive.
  8. Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
  9. Any condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
  10. A serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
  11. A major surgical procedure, open biopsy, or significant traumatic injury ≤28 days of beginning treatment, or anticipation of the need for major surgery during the course of the study.
  12. 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. Patients may not receive any other investigational or anti-cancer treatments while participating in this study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01113632

Locations
United States, California
Los Robles
Thousand Oaks, California, United States, 91360
United States, Florida
Florida Cancer Specialists
Ft. Myers, Florida, United States, 34236
Woodlands Medical Specialists
Pensacola, Florida, United States, 32503
United States, Georgia
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
United States, Indiana
Providence Medical Group
Terre Haute, Indiana, United States, 47802
United States, Missouri
St. Louis Cancer Care
Chesterfield, Missouri, United States, 63017
United States, New Hampshire
Portsmouth Regional Hospital
Portsmouth, New Hampshire, United States, 03801
United States, New Jersey
Hematology-Oncology Associates of Northern NJ
Morristown, New Jersey, United States, 07960
United States, Ohio
Oncology Hematology Care
Cincinnati, Ohio, United States, 45242
The Ohio State University
Columbus, Ohio, United States, 43210
United States, South Carolina
South Carolina Oncology Associates
Columbia, South Carolina, United States, 29210
United States, Tennessee
Chattanooga Oncology Hematology Associates
Chattanooga, Tennessee, United States, 37404
Tennessee Oncology
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
SCRI Development Innovations, LLC
GlaxoSmithKline
Investigators
Study Chair: Ian Flinn, M.D. SCRI Development Innovations, LLC
  More Information

No publications provided

Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT01113632     History of Changes
Other Study ID Numbers: SCRI CLL 11
Study First Received: April 28, 2010
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by SCRI Development Innovations, LLC:
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Ofatumumab

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014