Safety and Anti-Disease Activity of CHR-2797 (Tosedostat) in Elderly and/or Treatment Refractory Patients With Acute Myeloid Leukemia (AML) and Multiple Myeloma (MM)

Multiple Myeloma Clinical Trial

Official title: A Phase I-II Study to Evaluate the Safety, Tolerability and Anti-Disease Activity of the Aminopeptidase Inhibitor, CHR-2797, in Elderly and/or Treatment Refractory Patients With Acute Myeloid Leukemia or Multiple Myeloma

Status Completed

Clinical Trial Summary

This is an open-label, non-randomised, multi-centre phase I-II study of CHR-2797 administered orally once a day. The study involves two distinct phases:

• Phase I: an open-label, dose-escalating phase of the study to explore the safety, tolerability, and pharmacokinetics (PK) of CHR-2797.

• Phase II: the recommended dose level of CHR-2797, as determined in phase I, will be administered to a further cohort of approximately 40 patients to determine whether CHR-2797 has sufficient biological activity against the disease(s) under study.

Clinical Trial Description

This is an open-label, non-randomised, multi-centre phase I-II study of CHR-2797 administered orally once a day. The study involves two distinct phases:

Phase I: an open-label, dose-escalating phase of the study to explore the safety, tolerability, and pharmacokinetics (PK) of CHR-2797. Cohorts of 3-6 patients each will be treated with escalating, once daily, oral doses of CHR-2797 for 84 days (12 weeks), of which the first 28 days constitute the dose finding/ DLT phase. The starting dose will be 60 mg once daily. Doses will be increased in a stepwise fashion by around 40 percent per step until the MTD is reached. The proportion of patients with Multiple Myeloma will be limited to one third: one per cohort of 3 or 2 per cohort of 6. It is anticipated that 24-30 patients will be enrolled in the phase I portion of the trial. A decision will be made with regard to the disease indication to be tested in phase II (either AML/MDS or MM or both), after completion of phase I, or following definition of MTD.

Phase II: the recommended dose as determined in phase I, will be administered for 84 days to a maximum of 40 patients. The primary objective is to determine whether CHR-2797 has sufficient biological activity against the disease(s) under study. A multinomial stopping rule has been included in the design that incorporates objective responses and early progression into a decision to stop or continue this phase I/II trial. An interim assessment will be performed after 15 patients have received the maximum acceptable dose (MAD) dose of CHR-2797 with clearly defined early stopping rules.

There will be a clinical conference at the end of every cohort in the phase I portion of the study, between phase I and II and after the first 15 patients have completed therapy in phase II. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Multiple Myeloma
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Neoplasms, Plasma Cell
• Preleukemia

• NCT number: NCT00689000
• Study type: Interventional
• Source: Chroma Therapeutics
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 2006
• Completion date: December 2007