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

Myelodysplastic Syndromes Clinical Trial

— GREFFE  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03659084
• Other study ID #: 2013.812
• Status: Recruiting
• Start date: April 2016
• Est. completion date: April 2020

Study information

• Verified date: September 2018
• Source: Hospices Civils de Lyon
• Contact: Mauricette MICHALLET, MD, PhD
• Phone: 33(0)478862220
• Email: mauricette.michallet[@]lyon.unicancer.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: April 2020
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Myeloid Leukemia
• Preleukemia
• Syndrome

Intervention

Drug:
• EXJADE
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.

Locations

Country	Name	City	State
France	Centre Hospitalier Lyon Sud	Pierre-Bénite

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

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