A Phase I/II Study to Assess the Safety and Tolerability of APO866 for the Treatment of Refractory B-CLL

• Status: Completed
• Trial end date: 2009-04-01
• Target enrollment: 0
• Participant gender: All

Summary

This phase I/II study is designed to determine the safety and tolerability of APO866 for the treatment of refractory B-CLL not amenable to aHSCT. APO866 has shown to induce growth inhibition in cultures of a wide variety of human hematological malignant cells as well as in models with subcutaneously implanted human 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 is repeated every 4 weeks. In this study patients will receive only one cycle of treatment and the study endpoints will be evaluated 4 weeks after the start of infusion. Patients will be followed up for 12 weeks for safety.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Onxeo

Criteria

Inclusion Criteria:

• Immunophenotypic (monoclonal population of mature CD5+, CD19+, CD23+) confirmed diagnosis of B-CLL

• Diagnosis of progressive symptomatic B-CLL requiring therapy (Revised NCI-sponsored Working Group guidelines for CLL

• Relapsed or refractory disease or intolerant to ≥ 2 prior systemic therapy. (containing either a purine analog or an alkylating agent). Patient is not amenable to aHSCT

• ECOG Performance Status < 2

• Age > 18 years, of either sex

• Female patients with childbearing potential must be using a hormonal contraceptive, intra uterine device, diaphragm with spermicide or condom with spermicide for the duration of the study. Women of childbearing potential must have a negative serum or urinary hCG pregnancy test within 7 days prior to Study Day 1 (SD1)

• Male patients, who are not surgically sterile, must use a condom with spermicide for the duration of the study and 3 months thereafter

• Have given written informed consent, prior to any study related procedure not part of the patient's normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.

Exclusion Criteria:

• Have participated in any other investigational study or received an experimental therapeutic procedure considered to interfere with the study in the 4 weeks preceding SD1

• Use of prohibited medication due to CYP3A4 metabolism of APO866, as specified in Section 6.6.2. concomitant use of these drugs will not be allowed during the study

• Uncontrolled medical conditions, requiring surgical or pharmacological treatment (exceptions must be approved by the Medical Responsible of the study)

• Active infection requiring systemic antibiotics

• Serious concomitant disease (e.g. significant cardiac disease)

• History of second cancer that was treated with curative intent and in complete remission for < 5 years, with the exception of basal cell carcinoma or cervical cancer in situ

• Inadequate bone marrow function: platelets < 75x10^9/L without transfusion in the preceding 2 weeks, ANC < 1,0x10^9/L without growth factor support, abnormal coagulation APTT and PT

• Platelet-refractory state due to platelet alloimmunization

• Inadequate liver function: total bilirubin > 1.5x upper limit of normal values (ULN), AST, ALT, or alkaline phosphatase > 2.5x ULN

• Inadequate renal function: serum creatinine > 1.5x ULN

• Retinopathy, history of retinal laser surgery, or an ERG < 50% of normal

• Pregnant or lactating female

• Known allergy to reagents in the study drug (APO866 or propylene glycol).