Clinical Trial: A Study of APO866 for the Treatment of Cutaneous T-cell Lymphoma
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: A Multicenter Open Label Phase II Study of to Assess the Efficacy and Safety of APO866 in the Treatment of Patients With Refractory or Relapsed Cutaneous T-cell Lymphoma
Brief Summary: This phase II study is designed to determine the efficacy and safety of APO866 for the treatment of patients with advanced forms of cutaneous T-cell lymphoma (CTCL). APO866 has shown to induce growth inhibition in cultures of human CTCL cells as well as in animal models with subcutaneously implanted human CTCL tumors. APO866 was considered to be safe and well-tolerated in a phase I study that treated 24 patients with advanced cancer. APO866 is administered by intravenous infusion continuously for 96 hours and that is repeated every 4 weeks. Patients will receive 3 cycles of treatment and the primary efficacy endpoint will be assessed at Week 16. patients will be followed up for 12 months
Detailed Summary:
CTCL is the most frequent occurring cutaneous non-Hodgkin lymphoma characterized by an indolent and protracted course of patches, plaques and tumors. It is highly symptomatic, debilitating, disfiguring and impacting on the patient's quality of life. The treatment strategy for CTCL is based on the exact diagnosis including the stage of disease and aims to preserve cellular immune function, while achieving an anti-tumor effect. Given the nature of the disease and the cumulative and additive toxicities of treatments used, the intensity and duration of long-term therapy is limited.
APO866 is novel drug that induces cell death by specifically inhibiting the biosynthesis of NAD+ from niacinamide, which is essential for the cellular metabolism, protein modification (e.g. PARP mediated DNA repair, sirtuins (histone deacetylation)) and Calcium dependent messenger synthesis. APO866 is not subject to the commonly known mechanisms of MDR. Its activity is cell cycle independent. APO866 exerted high anti-tumor activity on a broad range of different tumor cells derived from both human solid cancers and leukemias in vitro and on large number of human xenografts in nude mice and rats in vivo. Hematologic cancer cells were highly sensitive to APO866. Lymphocytes are the most sensitive normal cells to APO866 resulting to lymphocytopenia and reticulocytopenia in rats, monkeys and cancer patients. Furthermore, APO866 may have anti-angiogenic properties as shown in vivo and in patients.
APO866 has shown to induce, at low nM level, growth inhibition of human Myla CTCL cells as well as in human subcutaneous xenografts of Myla CTCL in Balb-C nude mice.
APO866 was investigated in 24 patients with advanced cancers in a phase I study aiming to determine the DLT and MTD. Treatment was well tolerated an
Sponsor: Onxeo
Current Primary Outcome: The proportion of eligible patients with refractory or relapsed CTCL whom have a complete response or partial response on cutaneous lesions (Tumor Burden Index) and extra-cutaneous disease. [ Time Frame: Week 16 ]
Original Primary Outcome: The proportion of eligible patients with refractory or relapsed CTCL whom have a complete response or partial response on cutaneous lesions (Tumor Burden Index) and extra-cutaneous disease.
Current Secondary Outcome: Safety and tolerability, time to response, duration of overall response, duration of stable disease and time to treatment failure. [ Time Frame: Week 16 ]
Original Secondary Outcome: Safety and tolerability, time to response, duration of overall response, duration of stable disease and time to treatment failure.
Information By: Onxeo
Dates:
Date Received: February 5, 2007
Date Started: February 2007
Date Completion:
Last Updated: July 7, 2015
Last Verified: July 2015
