Previously Treated CD20+ B-cell Malignancies Clinical Trial
Official title:
A Phase I Study of Subcutaneous Ocaratuzumab (Fab- and Fc-engineered Anti-CD20 Monoclonal Antibody) in Patients With Previously Treated CD20+ B-Cell Malignancies
| Verified date | February 2014 |
| Source | Mentrik Biotech, LLC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | United States: Food and Drug Administration |
| Study type | Interventional |
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.
| Status | Not yet recruiting |
| Enrollment | 9 |
| Est. completion date | |
| Est. primary completion date | December 2015 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
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. |
Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United States | Universtity of Texas Southwestern Medical Center | Dallas | Texas |
| Lead Sponsor | Collaborator |
|---|---|
| Mentrik Biotech, LLC |
United States,
Forero-Torres A, de Vos S, Pohlman BL, Pashkevich M, Cronier DM, Dang NH, Carpenter SP, Allan BW, Nelson JG, Slapak CA, Smith MR, Link BK, Wooldridge JE, Ganjoo KN. Results of a phase 1 study of AME-133v (LY2469298), an Fc-engineered humanized monoclonal anti-CD20 antibody, in Fc?RIIIa-genotyped patients with previously treated follicular lymphoma. Clin Cancer Res. 2012 Mar 1;18(5):1395-403. doi: 10.1158/1078-0432.CCR-11-0850. Epub 2012 Jan 5. — View Citation
Tobinai K, Ogura M, Kobayashi Y, Uchida T, Watanabe T, Oyama T, Maruyama D, Suzuki T, Mori M, Kasai M, Cronier D, Wooldridge JE, Koshiji M. Phase I study of LY2469298, an Fc-engineered humanized anti-CD20 antibody, in patients with relapsed or refractory follicular lymphoma. Cancer Sci. 2011 Feb;102(2):432-8. doi: 10.1111/j.1349-7006.2010.01809.x. Epub 2011 Jan 12. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | No | |
| Primary | 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 | No | |
| Secondary | 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 | Yes | |
| Secondary | 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 | Yes |