NCT01063257

Clofarabine in High Risk Myelodysplastic Syndrome (MDS)

A Phase I/II Multicenter Study of IV Clofarabine in Patients With High-Risk Myelodysplastic Syndrome Who Have Failed Therapy With Azacitidine: the NIDEVOL Study

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 76 (actual)
• Sponsor: Groupe Francophone des Myelodysplasies · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study aims to determine the maximal tolerated dose (MTD) and dose limiting toxicities (DLTs) of low dose IV clofarabine for MDS patients after treatment failure of azacitidine.

Detailed description

The study is an open-label, 3+3 dose-escalation, phase I/II study.The duration of enrollment in the phase I study is 12 months. Fourteen patients will be enrolled at the RD using the selected dosing in each cohort, for an enrollment period of 12 months. Each patient may receive up to 8 courses, every 4 to 8 weeks in a D1-D5 schedule or every other day from D1 to D10. Each patient will be followed for up to 24 months. Primary endpoint of the phase I part: * To determine the maximal tolerated dose (MTD) and dose limiting toxicities (DLTs) of increased doses of IV clofarabine administered either daily from D1 to D5 for a 28 to 56 day-course or every other day from D1 to D10 for a 28 to 56 day-course. Secondary endpoints: * To determine response rates, as defined by the 2006 modified IWG criteria, associated with the two different dosing and scheduling of clofarabine in patients with high-risk MDS or AML patients with less than 30% marrow blasts (RAEB-T in FAB MDS classification), previously treated by azacitidine and without erythroid response after 6 cycles of azacitidine. * To evaluate response duration, time to IPSS progression, and loss of RBC transfusion independence in these patients. * To evaluate hospitalization duration, rates of rehospitalization for non-hematological toxicities, severe bleeding or febrile neutropenia. If treatment is feasible the study will be extended to the phase II part. Study Objectives: Primary endpoint: * To confirm safety and hematological toxicity in 14 additional patients. Secondary endpoints * To evaluate response duration, time to IPSS progression, and loss of RBC transfusion independence in these patients. * To evaluate hospitalization duration, rates of rehospitalization for non hematological toxicities, severe bleeding or febrile neutropenia. * To determine the response rate as defined by the 2006 modified IWG criteria.

Conditions

• Myelodysplastic Syndrome

Interventions

Type	Name	Description
DRUG	Clofarabine	The dosage of Clofarabine will be gradually augmented in a 3+3 design for each following dose level: DL1 - 5mg/m2/d, DL2 - 7.5mg/m2/d, DL3 - 10mg/m2/d, DL4 - 12.5mg/m2/d (This dose may not be reached and is an optional dose level in case the MTD is not reached before and depending on further data from the ongoing MDS Phase IIa oral formulation trial). The DLa will be the following: DL1a - 2.5mg/m2/d, DL2a - 6.5mg/m2/d, DL3a - 8.5mg/m2/d, DL4a - 11.5mg/m2/d (In case of activation of the DL4 step). Dose levels 1a, 2a and 3a will be used for de-escalation.

Timeline

• Start date: 2010-04-01
• Primary completion: 2014-03-01
• Completion: 2014-03-01
• First posted: 2010-02-05
• Last updated: 2014-03-19

Locations

5 sites across 1 country: France