Study of the Outcome of Patients With Acute Myeloblastic Leukemia and Myelodysplastic Syndrome Receiving Iron Chelation Therapy After Allogeneic Hematopoietic Stem Cell Transplantation

NCT03659084 — Unknown, 150 participants, Hospices Civils de Lyon

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Multicenter Prospective Observational Study of the Outcome of Patients With Acute Myeloblastic Leukemia (AML) and Myelodysplastic Syndrome (MDS) Receiving Iron Chelation Therapy (Exjade) After Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)

Registry	NCT03659084, acronym GREFFE
Status	Unknown
Study type	Observational
Enrollment	150 (Estimated)
Sponsor	Hospices Civils de Lyon (Other)
Conditions	Myeloid Leukemia, Myelodysplastic Syndromes
Interventions	EXJADE (Drug)
Dates	start 2016-04-01, primary completion 2018-04-01, completion 2020-04-01 (estimated), first posted 2018-09-06, last updated 2018-09-06
Locations	1 site in France

-Summary

Iron chelation, mostly associated with multiple red blood cell transfusion, is relatively common in patients with hematological malignancies receiving allo-HSCT.

This multicenter prospective observational study is designed to establish the impact of iron chelation on relapse after allo-HSCT in patients with acute myeloid leukemia and myelodysplastic syndrome. The investigators will compare the results obtained in the prospective study to those observed in a historical retrospective cohort of paired patients who did not receive chelation. Given our clinical experience and literature results, the investigators will evaluate the Exjade chelator. Although not demonstrated, the presence of mutations of the HFE gene could play an indirect role on leukemogenesis by promoting overload. It is therefore important to evaluate the status in this patient population.

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+Arms and interventions

EXJADE (Drug): The patient having given his consent, will begin the Exjade at 10 mg / kg per day if the ferritin level reached 1000 ng / ml at 6 months after allograft, for a minimum duration of three months and up to 6 months. The iron parameters will be evaluated at 3, 6, 9, 12, 18 and 24 months after the beginning of the exjade treatment. The evaluation of the disease will be carried out according to the practices of the center. It is recommended to have a washout period of one week between stopping the ciclosporin and the beginning of treatment by exjade.

+Outcome measures

Primary outcomes

Impact of iron chelation on relapse-free survival rate [At 2 years]: Relapse-free survival will be defined as the number of days between the date of diagnosis and the date of death and / or relapse (or censored at the end of follow-up).

Secondary outcomes

Comparison of relapse-free survival after allograft of chelated patients to allografted patients not receiving chelation. [At 2-year]: Matching variables will include disease type (AML or MDS), prognostic factors (cytogenetics, molecular biology, age), donor type / matching, and type of conditioning.
Cumulative incidence of GVHD [3 months, 1 and 2 years]: Acute and chronic GVHD date and maximum grade using international classification
Rate of infection [Through study completion, an average of 4 years]: during the observation period
Hematological toxicity during administration of Exjade [Through study completion, an average of 4 years]: Hemoglobin level; Current average frequency of transfusions
Non-hematological toxicity during administration of Exjade [Through study completion, an average of 4 years]: Ferritinemia
Non-hematological toxicity during administration of Exjade [Through study completion, an average of 4 years]: Transferrin

+Eligibility

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* adults older than 18 years old
* Patients with AML or MDS in complete remission receiving CSH transplantation from a related or unrelated donor and after myeloablative or non-myeloablative conditioning.
* Patients with iron overload defined by at least one ferritinemia> 1000 μg / L in the 6th month after CSH allograft
* Creatinine less than 1.5 x ULN; ALAT and ASAT <2 x ULN
* Patients giving their informed consent (prior to performing any study procedure)

Exclusion Criteria:

* Hypersensitivity to the Exjade
* Association with another iron chelator
* Proteinuria> 1g / 24h
* Acute and chronic hepatitis (B and C viruses); HIV
* Extended corrected QT
* History of ocular toxicity related to iron chelation treatment
* Gastrointestinal Abnormal Absorption of Oral Medications
* Pregnancy and lactation

+Locations (1)

Facility	City	Country	Status
Centre Hospitalier Lyon Sud	Pierre-Bénite	France	Recruiting

+Investigators

Mauricette MICHALLET, MD, Principal investigator, Hospices Civils de Lyon