Results from a clofarabine-busulfan-containing, reduced-toxicity conditioning regimen prior to allogeneic stem cell transplantation: the phase 2 prospective CLORIC trial.

Abstract

We prospectively evaluated the safety and efficacy of a clofarabine, intravenous busulfan and antithymocyte globulin-based reduced-toxicity conditioning (CloB2A2) regimen before allogeneic stem cell transplantation. Thirty high-risk patients (median age: 59 years; acute myeloid leukemia n=11, acute lymphoblastic leukemia n=13; myelodysplastic syndrome n=5, bi-phenotypic leukemia n=1) were included in this phase 2 study. At time of their transplant, 20 and seven patients were in first and second complete remission, respectively, while three patients with myelodysplastic syndrome were responding to chemotherapy or who had not been previously treated. The CloB2A2 regimen consisted of clofarabine 30 mg/m(2)/day for 4 days, busulfan 3.2 mg/kg/day for 2 days and antithymocyte globulin 2.5 mg/kg/day for 2 days. The median follow-up was 23 months. Engraftment occurred in all patients. The 1-year overall survival, leukemia-free survival, relapse incidence and non-relapse mortality rates were 63±9%, 57±9%, 40±9%, and 3.3±3%, respectively. Comparing patients with acute myeloid leukemia/myelodysplastic syndrome versus those with acute lymphoblastic leukemia/bi-phenotypic leukemia, the 1-year overall and leukemia-free survival rates were 75±10% versus 50±13%, respectively (P=0.07) and 69±12% versus 43±13%, respectively (P=0.08), while the 1-year relapse incidence was 25±11% versus 57±14%, respectively (P=0.05). The CloB2A2 regimen prior to allogeneic stem cell transplantation is feasible, allowing for full engraftment and low toxicity. Disease control appears to be satisfactory, especially in patients with acute myeloid leukemia/myelodysplastic syndrome. The trial was registered at www.clinicaltrials.gov no. NCT00863148.

• Authors: Patrice Chevallier, Myriam Labopin, Gérard Socié, Reza Tabrizi, Sabine Furst, Bruno Lioure, Thierry Guillaume, Jacques Delaunay, Régis Peffault de La Tour, Stéphane Vigouroux, Jean El-Cheikh, Didier Blaise, Mauricette Michallet, Karin Bilger, Noel Milpied, Philippe Moreau, Mohamad Mohty
• Journal: Haematologica (Haematologica) Vol. 99 Issue 9 Pg. 1486-91 (Sep 2014) ISSN: 1592-8721 [Electronic] Italy
• PMID: 24951467 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© Ferrata Storti Foundation.

Chemical References

• Adenine Nucleotides
• Antilymphocyte Serum
• Arabinonucleosides
• Myeloablative Agonists
• Clofarabine
• Busulfan

Topics

• Adenine Nucleotides (therapeutic use)
• Adult
• Aged
• Antilymphocyte Serum (therapeutic use)
• Arabinonucleosides (therapeutic use)
• Busulfan (therapeutic use)
• Clofarabine
• Drug Administration Schedule
• Female
• Graft Survival (immunology)
• Hematopoietic Stem Cell Transplantation
• Humans
• Leukemia, Biphenotypic, Acute (immunology, mortality, pathology, therapy)
• Leukemia, Myeloid, Acute (immunology, mortality, pathology, therapy)
• Male
• Middle Aged
• Myeloablative Agonists (therapeutic use)
• Myelodysplastic Syndromes (immunology, mortality, pathology, therapy)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (immunology, mortality, pathology, therapy)
• Recurrence
• Survival Analysis
• Transplantation Conditioning (methods)
• Transplantation, Homologous