Clofarabine Salvage Therapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia
All patients are scheduled for at least one cycle of induction therapy with CLARA. CLARA
contains clofarabine 40 mg/m2 (1 hr infusion) days 1-5 followed 3 hours after the end of
infusion by intermediate dose cytarabine 1 g/m2 (2 hrs infusion) days 1-5. Patients with
moderate early response (reduced marrow blast count but ≥10% at day 15) or patients with
progressive disease during delayed hematologic recovery (beyond day 42) may receive
re-induction therapy similar to the first cycle induction therapy.
Study treatment comprises up to two cycles of induction therapy and one to two cycles of
consolidation chemotherapy for patients without a donor. Consolidation therapy is reduced by
25% and consists of clofarabine 40 mg/m2 (1 hr infusion) days 1-4 followed 3 hours after the
end of infusion by intermediate dose cytarabine 1 g/m2 (2 hrs infusion) days 1-4.
Patients for whom a donor can be identified may proceed to allogeneic HCT after CLARA I
adopting the concept of allogeneic HCT in aplasia. Patients for whom donor search is more
time consuming should proceed to allogeneic HCT once a donor has been identified.
Patients who have achieved a response after the last cycle of CLARA will receive clofarabine
as part of the conditioning regimen. Clofarabine and melphalan may only be given as
conditioning therapy to patients with HLA-compatible donors with a maximum of one mismatch
refering to the HLA-loci A, -B, -C and -DRB1. Conditioning therapy then contains clofarabine
30 mg/m2 (1 hr IV infusion) days -6 to -3 and melphalan 140 mg/m2 (1 hour IV infusion) on
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Rate of treatment success
Treatment success is defined as a complete remission (CR, CRi or CRchim) at final response assessment after having completed the study treatment. CR and CRi are defined according to standard criteria (ELN). Complete remission by chimerism (CR chim) is defined as a >95% overall donor chimerism assessed by STR-PCR in bone marrow and absence of extramedullary disease together with an absolute neutrophil count >0.5 /nL (500/μL).
To be evaluated 42 days after start of last cycle of chemotherapy containing clofarabine
Johannes Schetelig, MD
Universitätsklinikum Dresden, Med. Klinik und Poliklinik I, Study Alliance Leukemia
Germany: Federal Institute for Drugs and Medical Devices