Neoplasms

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Leukemia

Leukemia, Myeloid

Neoplasms by Histologic Type

Hematologic Diseases

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Fludarabine

Fludarabine phosphate

Busulfan

Thiotepa

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Immunologic Factors

Alkylating Agents

Antineoplastic Agents, Alkylating

Reduced toxicity conditioning regimen (thiotepa, busulfan, fludarabine and ATG) followed by unrelated cord blood allogeneic stem cell transplant for high risk myeloïd malignancies.

The conditioning regimen will include:

* IV Thiotepa (5 mg/Kg/day for 2 days) (Day -7 and -6)
* IV fludarabine (40 mg/m²/day for 4 days) (from Day-5 to day -2)
* IV Busulfan (Busilvex 130 mg/m2/day for 3 days) (Day-5, -4 and -3)
* IV Anti-thymocyte globuline (Thymogobuline®, 2.5 mg/kg/day for 2 days) (Day-3 and -2)

In patient with co-morbidities and/or older than 60 years, conditioning could be reduced after consulting the coordinator of the study:

* IV Thiotepa (5 mg/Kg/day for 2 days) (Day -6)
* IV fludarabine (40 mg/m²/day for 4 days) (from Day-5 to day -2)
* IV Busulfan (Busilvex 100 mg/m2/day for 3 days) (Day-5, -4 and -3)
* IV Anti-thymocyte globuline (Thymogobuline®, 2.5 mg/kg/day for 2 days) (Day-3 and -2)

IV Thiotepa (5 mg/Kg/day for 2 days) (Day -7 and -6) or IV Thiotepa (5 mg/Kg/day for 2 days) (Day -6)

IV Thiotepa

IV fludarabine (40 mg/m²/day for 4 days) (from Day-5 to day -2)

IV Fludarabine

(Busilvex 130 mg/m2/day for 3 days) (Day-5, -4 and -3) or (Busilvex 100 mg/m2/day for 3 days) (Day-5, -4 and -3)

IV Busulfan

(Thymogobuline®, 2.5 mg/kg/day for 2 days) (Day-3 and -2)

IV Anti-thymocyte globuline

Marie Thérèse RUBIO

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).

Reduced Toxicity Conditioning Prior to Unrelated Cord Cell Transplantation for High Risk Myeloid Malignancies

Cumulative incidence of NRM at 12 months after transplantation : Safety and efficacy of the pre-transplant reduced toxicity conditioning regimen

Incidence of neutrophil engraftment (day and proportion of patients reaching neutrophils \>0.5x109/L); and platelets recovery (day and proportion of patients reaching platelets \> 20 x 109 / L without transfusion) after transplantation

Incidence and severity of acute GVHD (diagnosed and graded as standard criteria)

Incidence and severity of chronic GVHD (diagnosed and graded as standard criteria detailed )

Incidence of disease relapse at one year after transplantation (relapse is defined on the basis of morphologica evidence of leukemic cells in the bone marrow or other sites)

Evaluation of the quality of life (using a french translation of the FACT-BMT (version 4.0)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Reduced Toxicity Conditioning Prior to Unrelated Cord Cell Transplantation for High Risk Myeloid Malignancies	NCT02333838	Leukemia, Myelo...	IV Thiotepa IV Fludarabine IV Busulfan IV Anti-thymocy...	18 Years - 65 Years	Assistance Publique - Hôpitaux de Paris
Reduced Toxicity Conditioning Prior to Unrelated Cord Cell Transplantation for High Risk Myeloid Malignancies	NCT02333838	Leukemia, Myelo...	IV Thiotepa IV Fludarabine IV Busulfan IV Anti-thymocy...	18 Years - 65 Years	Assistance Publique - Hôpitaux de Paris

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