Clinical trial NCT01113632: Ofatumumab for Patients With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Keywords: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Ofatumumab
Lead sponsor: SCRI Development Innovations, LLC
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2010-04-30
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 18 months
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: 18 months
measure: Number of Complete Responses
timeFrame: 18 Months
measure: Number of Partial Responses
timeFrame: 18 Months
measure: Safety of the Treatment Regimen
timeFrame: 18 Months
Other outcomes:
Locations:
city: Thousand Oaks
country: United States
facility: Los Robles
state: California
city: Ft. Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Pensacola
country: United States
facility: Woodlands Medical Specialists
state: Florida
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Terre Haute
country: United States
facility: Providence Medical Group
state: Indiana
city: Chesterfield
country: United States
facility: St. Louis Cancer Care
state: Missouri
city: Portsmouth
country: United States
facility: Portsmouth Regional Hospital
state: New Hampshire
city: Morristown
country: United States
facility: Hematology-Oncology Associates of Northern NJ
state: New Jersey
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Columbia
country: United States
facility: South Carolina Oncology Associates
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Oncology Hematology Associates
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
Study officials:
affiliation: SCRI Development Innovations, LLC
name: Ian Flinn, M.D.
role: STUDY_CHAIR
References: