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
Overview
- Phase
- Phase 2
- Intervention
- Ofatumumab
- Conditions
- Chronic Lymphocytic Leukemia
- Sponsor
- SCRI Development Innovations, LLC
- Enrollment
- 77
- Locations
- 13
- Primary Endpoint
- Overall Response Rate (ORR)
- Status
- Completed
- Last Updated
- 9 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •CD20+ B-cell chronic lymphocytic leukemia (B-CLL) or small lymphocytic lymphoma according to NCI criteria (see Appendix B).
- •Previously untreated CLL or small lymphocytic lymphoma (SLL).
- •Patients must require treatment according to NCI-Working Group guidelines (see Appendix C).
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤2 (see Appendix A).
- •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
- •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.
- •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.
Exclusion Criteria
- •Previous therapy for CLL/SLL. (Patients who have received steroids or IVIG for autoimmune complications of CLL are eligible).
- •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).
- •Active bacterial or viral infection, or infection requiring intravenous antibiotic treatment at the time of accrual.
- •Central nervous system lymphoma/CLL.
- •Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (i.e., Richters transformation).
- •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.
- •Patients who are HepB sAg positive and/or HepB cAb positive.
- •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.
- •Any condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
- •A serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
Arms & Interventions
Ofatumumab 1000mg
Ofatumumab 300mg IV Day 1 followed by ofatumumab 1000mg weekly for a total of 8 weeks
Intervention: Ofatumumab
Ofatumumab 2000mg
Ofatumumab 300mg IV Day 1 followed by ofatumumab 2000mg weekly for a total of 8 weeks
Intervention: Ofatumumab
Outcomes
Primary Outcomes
Overall Response Rate (ORR)
Time Frame: 18 months
The Number of Patients Who Experience an Objective Benefit From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Secondary Outcomes
- Number of Complete Responses(18 Months)
- Safety of the Treatment Regimen(18 Months)
- Number of Partial Responses(18 Months)
- Progression-free Survival (PFS)(18 months)