Phase I Study of Subcutaneous Ocaratuzumab in Patients With Previously Treated CD20+ B-Cell Malignancies

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I Study of Subcutaneous Ocaratuzumab (Fab- and Fc-engineered Anti-CD20 Monoclonal Antibody) in Patients With Previously Treated CD20+ B-Cell Malignancies

Conditions
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Previously Treated CD20+ B-cell Malignancies

Intervention / Treatment
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* Biological: ocaratuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>SC ocaratuzumab 40 mg weekly x 4 doses | Biological: ocaratuzumab<br> <br> * Other names: AME-133v, LY2469298;|
| Experimental: Cohort 2<br>SC ocaratuzumab 80 mg weekly x 4 doses | Biological: ocaratuzumab<br> <br> * Other names: AME-133v, LY2469298;|
| Experimental: Cohort 3<br>SC ocaratuzumab 80 mg weekly x 8 doses | Biological: ocaratuzumab<br> <br> * Other names: AME-133v, LY2469298;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters following SC ocaratuzumab administration such as area under the curve, maximum serum drug concentration, and elimination half life |  | Every office visit throughout the study for up to 12 months | 
| Pharmacodynamic profile of B-cell depletion and re-population as measured by CD19+ peripheral blood B lymphocyte count |  | Baseline, day 1 and 8, 1 mon, 3 mon, 6 mon, and 12 mon post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of SC ocaratuzumab administration as described by the incidence of adverse events such as local injection site reactions or laboratory abnormalities |  | Every office visit throughout the study for up to 12 months | 
| Immunogenicity as measured by the incidence, titre of human anti-human antibody (HAHA) immune response |  | Baseline, 1 mon, 2 mon, 3 mon, 6 mon, and 12 mon post-treatment |