NCT01813838

GFM-Acadesine: A Phase I-II Trial of Acadesine

A Phase I-II Trial of Acadesine in IPSS High and Int-2 SMD, LAM With 20-30% Marrow Blasts and CMML Type 2 Not Responding to Azacitidine or Decitabine for at Least 6 Courses or Relapsing After a Response

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: Groupe Francophone des Myelodysplasies · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

A phase I-II trial of Acadesine in IPSS high and int 2 myelodysplastic syndromes, acute myeloid leukemia with 20-30% marrow blasts and chronic myelomonocytic leukemia type 2 not responding to Azacitidine or Decitabine for at least 6 courses or relapsing after a response: Patients will receive 6 treatment cycles unless disease progression, transformation, or unacceptable toxicity occurs, or the patient refuses to continue participating in the study. Efficacy will be assessed at the end of the 2nd, 4th and 6th cycles. After 6 cycles, patients demonstrating a response (CR, PR, marrow CR, or HI) will be able to continue with cycles of Acadesine (at the same dose as in the preceding cycles, depending on their cohort) until progression.

Detailed description

Primary objectives Phase I: To determine the maximal tolerated dose (MTD) and dose limiting toxicities (DLTs) of increasing doses of IV Acadesine administered on D1, D3, D5, D8, D10 and D12 of 28 to 56 day-courses Phase II: To confirm safety and hematological toxicity in 18 additional patients Secondary objectives: Phase I: * To determine response rates, as defined by the 2006 modified IWG criteria, * 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. Phase II: To determine * response rate as defined by the 2006 modified IWG criteria * toxicity profile and safety * response duration * rate of progression to AML * overall survival

Conditions

• SMD

Interventions

Type	Name	Description
DRUG	ACADESINE 140mg/kg/d	3 patients will be included at the initial dose of 140mg/kg/d. In absence of toxicity, 3 additional patients will be included at the higher dosage. In case of 1/3 toxicity, 3 additionnal patients will be included at the same dose level, currently 140mg/kg/d. In case of toxicity in 2 or more patients, the dose of acadesine will be reduced at the the dose of 85mg/kg/d
DRUG	ACADESINE 210mg/kg/d	3 patients will be included at the dose of 210mg/kg/d. In absence of toxicity, 3 additional patients will be included at the higher dosage. In case of 1/3 toxicity, 3 additionnal patients will be included at the same dose level, currently 210mg/kg/d. In case of toxicity in 2 or more patients, the dose of acadesine will be reduced at the the dose of 140mg/kg/d
DRUG	ACADESINE 315mg/kg/d	3 patients will be included at the dose of 315mg/kg/d. In case of 1/3 toxicity, 3 additionnal patients will be included at the same dose level, currently 315mg/kg/d. In case of toxicity in 2 or more patients, the dose of acadesine will be reduced at the the dose of 210mg/kg/d

Timeline

• Start date: 2013-06-01
• Primary completion: 2013-06-01
• Completion: 2015-06-01
• First posted: 2013-03-19
• Last updated: 2016-11-08

Locations

17 sites across 1 country: France