Rituximab Plus CAMPATH in Patients With Relapsed/Refractory Low-Grade or Follicular, CD20-positive, B-cell NHL

Phase I/II Study of Rituximab Plus CAMPATH in Patients With Previously Treated Relapsed or Refractory Low-Grade Follicular, CD20-positive, B-cell Non-Hodgkin's Lymphoma

The purpose of this study is to determine the optimal dose of subcutaneous CAMPATH when used in combination with rituximab for patients with relapsing or refractory, low-grade or follicular, CD-20-positive, B-Cell non-Hodgkin's Lymphoma. Safety will be the primary objective of phase I, while the primary objective of phase II will be to determine overall response.

This study is being conducted in 2 parts. Phase I will involve dose escalation of subcutaneous CAMPATH (SQ) given 3 times per week in combination with weekly doses of rituximab (375mg/m2) for a maximum of 8 weeks in order to determine the maximum tolerated dose (MTD). In Phase II patients will be treated with SQ CAMPATH at the MTD plus weekly rituximab (375mg/m2)for a maximum of 8 weeks with primary objective of defining Overall Response (OR) to this combination.

Inclusion Criteria:

• For the Phase I portion of the study, patients must have pathologically confirmed diagnosis of low-grade or follicular, CD20-positive, B-cell, non-Hodgkin's lymphoma that has relapsed or is refractory. For the Phase II portion of the study, patients must have a pathologically confirmed diagnosis of low-grade or follicular, CD20-positive, B-cell, non-Hodgkin's lymphoma (Follicular, predominantly small cleaved or follicular, mixed small cleaved and large cell, International Working Formulation classification B or C or REAL classification follicular center grade 1,2) that has relapsed or is refractory.
• Previously treated with at least one anti-cancer regimen for NHL
• Measurable disease (lesions that can be accurately measured in 2 dimensions by CT scan with a greatest transverse diameter of >/= to 2cm or palpable lesions with both diameters of 2cm or more)
• Life expectancy of at least 12 weeks
• WHO performance status or 0 or 1
• Adequate marrow and organ function (as defined in the protocol)
• Completed major surgery, radiotherapy, chemotherapy, immunotherapy or biotherapy/targeted therapies at least 4 weeks prior to study entry (6 weeks if treated with a nitrosourea or mitomycin). Patients must have recovered from all prior treatment toxicity to Grade 1 or less, exclusive of alopecia.

Exclusion Criteria:

• Prior combination therapy with rituximab and CAMPATH; prior therapy with either agent alone is permitted
• A history of a T-cell lymphoma
• Known AIDS-related HIV-positive lymphoma
• For the Phase II portion of the study (once MTD has been determined), bulky disease, ie, any single mass >10cm or circulating malignant cells of 25,000/uL or more
• Prior autologous bone marrow or stem cell transplant within 6 months of study entry
• Prior allogeneic bone marrow transplant or organ transplant
• Prior radiotherapy to the only site of measurable disease
• Medical condition requiring chronic use of oral, high-dose corticosteroids
• Use of investigational agents within 30 days of study enrollment
• Past history of anaphylaxis following exposure to humanized monoclonal antibodies
• Known, active, infection, including HIV positive
• Diagnosis of another malignancy within the previous five (5) years, unless the probability of recurrence of the prior malignancy is < 5%. Patients with curatively treated early stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin, cervical intraepithelial neoplasia (CIN), and patients with a history of malignant tumor in the past that have been disease-free for at least 5 years
• Active central nervous system (CNS) involvement with lymphoma
• Pregnant or nursing women
• Any significant concurrent disease or illness that would, in the opinion of the investigator, compromise patient safety or compliance, or interfere with the interpretation of study results
• Active hepatitis or a history of prior viral hepatitis B or C, or positive hepatitis B serologies without prior immunization