Phase I Study of Subcutaneous Ocaratuzumab in Patients With Previously Treated CD20+ B-Cell Malignancies
Ocaratuzumab is a third-generation, fully humanized IgG1 monoclonal antibody (mAb) targeting the CD20 surface marker on normal and malignant B lymphocytes. It has been optimized for an increased binding for CD20 and an enhanced antibody dependent cell medicated cytotoxicity (ADCC) effector function. A previous phase I / II study of intravenously (IV) administered ocaratuzumab in refractory / relapsed follicular lymphoma patients has concluded that ocaratuzumab is safe and well-tolerated at doses up to 375mg / m2 weekly for four weeks. In this proposed phase I study, ocaratuzumab will be administered subcutaneously to patients with previously treated CD20+ B-cell malignancies. Three dose levels (40 mg weekly x 4 doses, 80 mg weekly x 4 doses, and 80 mg weekly x 8 doses) will be investigated for safety, tolerability, pharmacokinetic, and pharmacodynamic analyses.
- Age >18 years;
- Histologically confirmed diagnosis of a CD20+ B-cell malignancy;
- Received at least one prior treatment regimen;historically documented CD20-positivity is acceptable;
- Appropriate for single agent study drug therapy as prescribed by this protocol;
- ECOG performance status 0 to 2;
- Adequate hematopoietic, renal, and hepatic functions defined as:
- Absolute neutrophil count greater than 1000 /mm³
- Platelet count greater than 75,000/mm³
- Hemoglobin greater than 8.5 g/dL
- Serum creatinine ≤ 1.5x upper limit of normal
- AST, ALT, and total bilirubin ≤ 3x upper limit of normal;
- Ability to understand and the willingness to sign a written informed consent document;
- Life expectancy of 6 months or greater.
- Anti-CD20 therapy within 4 weeks of enrollment;
- Systemic chemotherapy or immunotherapy within 14 days of enrollment;
- Chronic systemic steroid therapy defined as prednisone or equivalent 10 mg/day or greater;
- Systemic cytotoxic or immunosuppressive therapy to be administered concomitantly while participating on this study;
- Active infection, chronic or severe infection requiring ongoing antimicrobial therapy.
- Positivity for hepatitis B (defined as HepBs Antigen +), hepatitis C (defined as HepC Antibody +), or HIV; HIV positive patients on antiretroviral therapy will be excluded;
- History of allergic reactions attributed to compounds of similar chemical or biologic composition;
- Significant cardiac disease (New York Heart Association classes III or IV) or unstable angina despite medication;
- Women who are pregnant or breast-feeding;
- Women of child bearing potential who are unwilling to use effective contraception for the duration of the study drug administration and 6 months after final dose of drug is administered;
- Psychiatric illness/social situations that would limit compliance with study requirements;
- Participation in other investigational studies while enrolled on this trial.
Locations & Contacts
Trial Phase & Type
Mentrik Biotech, LLC
Secondary IDs NCI-2013-01989
Clinicaltrials.gov ID NCT01858181