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

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)

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.

Study Overview

• Status: Unknown
• Conditions: Myelodysplastic Syndromes; Myeloid Leukemia
• Intervention / Treatment: Drug: EXJADE

• Study Type: Observational
• Enrollment (Anticipated): 150

Contacts and Locations

• Study Contact: Name: Mauricette MICHALLET, MD, PhD; Phone Number: 33(0)478862220; Email: mauricette.michallet@lyon.unicancer.fr
• Study Contact Backup: Name: Mohamed ELHAMRI, PhD; Phone Number: 33 (0) 478 86 22 20; Email: mohamed.el-hamri@chu-lyon.fr

Study Locations

• France
  • Pierre-Bénite, France
    • Recruiting
    • Centre Hospitalier Lyon Sud
    • Contact: Mauricette Michallet, MD; Phone Number: +33 0 478 86 22 20; Email: mauricette.michallet@lyon.unicancer.fr
    • Contact: Mohamed ELHAMRI, PhD; Phone Number: +33 0478 86 22 20; Email: mohamed.el-hamri@chu-lyon.fr
    • Principal Investigator: Mauricette Michallet, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with acute leukemia (AML) or Myelodysplastic Syndrome (MDS) and iron overload with ferritinemia ≥ 1000 μg / l, 6 months after CSH allograft.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Cumulative incidence of GVHD	Acute and chronic GVHD date and maximum grade using international classification	3 months, 1 and 2 years
Rate of infection	during the observation period	Through study completion, an average of 4 years
Hematological toxicity during administration of Exjade	Hemoglobin level; Current average frequency of transfusions	Through study completion, an average of 4 years
Non-hematological toxicity during administration of Exjade	Ferritinemia	Through study completion, an average of 4 years
Non-hematological toxicity during administration of Exjade	Transferrin	Through study completion, an average of 4 years

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Mauricette MICHALLET, MD, Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): April 1, 2018
• Study Completion (Anticipated): April 1, 2020

Study Registration Dates

• First Submitted: August 27, 2018
• First Submitted That Met QC Criteria: September 3, 2018
• First Posted (Actual): September 6, 2018

Study Record Updates

• Last Update Posted (Actual): September 6, 2018
• Last Update Submitted That Met QC Criteria: September 3, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Myelodysplastic syndrome; Acute myeloid leukaemia; Iron Chelation Therapy (Exjade); allogeneic Hematopoietic Stem Cell transplantation (Allo-HSCT)
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferasirox
• Other Study ID Numbers: 2013.812

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No