Reduced Toxicity Conditioning Prior to Unrelated Cord Cell Transplantation for High Risk Myeloid Malignancies
Status:
Unknown status
Trial end date:
2019-05-01
Target enrollment:
Participant gender:
Summary
Allogeneic cord blood stem cell transplantation is a potentially curative therapy for
patients with haematological malignancies. We have extensive experience with the use of Cord
Blood Transplantation (CBT) in patients with advanced myeloid malignancies. In adults
however, the 40% Non-Relapse Mortality (NRM) rate observed after CBT conditioned with a
myeloablative conditioning has encouraged the development of CBT with Reduced Intensity
Conditioning (RIC). Our previous national CBT protocol (the Minicord French protocol -
NCT00797758) showed that RIC CBT can reduce NRM, but relapse remains the main post-transplant
event (>30% at one year). Thus, the development of reduced toxicity rather than RIC
conditioning for CBT is warranted in order to improve the outcome of such transplants by
limiting NRM and reducing relapse rate. The Fludarabine, ATG and intensified doses of IV
Busulfan (9.6 mg/Kg total dose) regimen is a well-established preparative regimen for
reduced-intensity/toxicity conditioning prior to allogeneic stem cell transplantation using
peripheral blood stem cells mobilized with G-CSF (ClinicalTrials.gov Identifier:
NCT00841724). However, such regimen is likely not sufficient to allow for CB cell
engraftment. Thiotepa is an alkylating and radio-mimetic agent with a large anti-tumor
activity including leukemic cells, the ability to cross the blood-brain barrier and to
improve engraftment of hematopoietic stem cells. This drug has been combined to usual
conditioning regimen without increasing the toxicity but improving the engraftment rate and
potentially reducing the relapse rate. Thus, in the context of adult CBT for high risk
myeloid malignancies, we propose to prospectively evaluate a reduced toxicity conditioning
based on the association of Thiotepa, Fludarabine, IV Busulfan and ATG with the objective to
achieve acceptable NRM rates, and to allow for improved anti-leukemic control based on the
cytotoxic component of the conditioning regimen itself, while waiting for the long term
immune-mediated disease control (GVL effect).