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

Phase 1

• Conditions: Previously Treated CD20+ B-cell Malignancies
• Interventions: Biological: ocaratuzumab

• Registration Number: NCT01858181
• Lead Sponsor: Mentrik Biotech, LLC

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-05-15
• Study First Submitted QC: 2013-05-20
• Study First Posted: 2013-05-21
• Status Verified: 2014-02
• Last Update Submitted: 2014-02-28
• Last Update Posted: 2014-03-03
• Study Start: 2015-01
• Primary Completion: 2015-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 9

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort 3	ocaratuzumab	SC ocaratuzumab 80 mg weekly x 8 doses
Cohort 1	ocaratuzumab	SC ocaratuzumab 40 mg weekly x 4 doses
Cohort 2	ocaratuzumab	SC ocaratuzumab 80 mg weekly x 4 doses

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

Universtity of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States