Clofarabine Salvage Therapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) (BRIDGE)
In relapsed or refractory AML allogeneic HCT is considered to be the only treatment by which long-term disease-free survival can be achieved. Despite this favorable prospect, even in younger patients with relapsed AML only about 40% of the patients reach allogeneic HCT. A number of factors contribute to this low rate of transplantation, among them moderate activity of the salvage regimens and accumulating toxicities which prevent from transplantation; Prospective clinical trials in this indication usually focus either on the rate of CR achieved after a defined number of cycles of salvage therapy or on transplantation modalities. The consequent integration of salvage therapy into a transplant strategy accounting for the time-dependent process of donor search has not been studied so far.
The objective of this study is to evaluate the safety and efficacy of clofarabine salvage therapy prior to allogeneic HCT.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Clofarabine Salvage Therapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia|
- Rate of treatment success [ Time Frame: To be evaluated 42 days after start of last cycle of chemotherapy containing clofarabine ] [ Designated as safety issue: No ]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).
- Rate of transplantation [ Time Frame: see evaluation of primary endpoint ] [ Designated as safety issue: No ]Rate of patients who finally proceeded to allogeneic HCT after bridging therapy with Clofarabine
- Adverse drug reactions [ Time Frame: see evaluation of primary endpoint ] [ Designated as safety issue: Yes ]Rate of adverse drug reactions.
- Treatment failure [ Time Frame: see evaluation of primary endpoint ] [ Designated as safety issue: Yes ]Cause specific analysis of treatment failure
|Study Start Date:||March 2011|
|Study Completion Date:||December 2013|
|Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Experimental: Single Arm
Induction therapy with clofarabine/cytarabine. Post-remission therapy with either allogeneic HCT after conditioning with clofarabine/melphalan if a donor is available, or clofarabine/cytarabine if no donor is available
Induction and consolidation therapy / conditioning therapy with Clofarabine
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 day -2.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01295307
|HELIOS Klinikum Bad Saarow|
|Bad Saarow, Germany|
|Klinikum Chemnitz gGmbH|
|University Hospital Carl Gustav Carus|
|Dresden, Germany, 01307|
|Klinikum der J. W. Goethe-Universität|
|Frankfurt am Main, Germany|
|Klinikum Mannheim GmbH|
|Klinikum Nürnberg Nord|
|Principal Investigator:||Johannes Schetelig, MD||Universitätsklinikum Dresden, Med. Klinik und Poliklinik I, Study Alliance Leukemia|