Evaluating Low-dose Deferasirox (DFX) in Patients With Low-risk MDS Resistant or Relapsing After ESA Agents (LODEFI)

Phase II Trial Evaluating Low-dose Deferasirox (DFX) in Patients With Low-risk (MDS) Myelodysplastic Syndrome Resistant or Relapsing After ESA Agents (LODEFI)

Patients with low-risk MDS verifying the eligibility criteria may be included in the study.

Study Overview

• Status: Recruiting
• Conditions: Myelodysplasia
• Intervention / Treatment: Drug: Deferasirox

Detailed Description

Patients will receive the number of DFX tablets (Exjade, cp film-coated, 90mg or 360mg), in relation to their body weight to be closer to 3.5mg / kg / d for 12 months.

At one month and six months of treatment, the residual plasma levels of DFX will be measured in patients (sent to the Bordeaux laboratory of Biochemistry, Pr Molimard) to allow the dosage to be adjusted (plasma objective of 3 μM).

At inclusion (J1) and at 6 months of treatment, a dosage of NTBI and hepcidine will be performed.

If patients become transfusion-dependent (≥) 2 packed red cells (RBP) per 2-month period evaluated over 6 months, they will stop low-dose DFX and go out of protocol to receive DFX at 20mg / kg (according to EMEA authorization) for iron chelation.

• Study Type: Interventional
• Enrollment (Anticipated): 39
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sophie Park; Phone Number: 0476762777; Email: Spark@chu-grenoble.fr
• Study Contact Backup: Name: Valérie Rolland; Phone Number: 0476765096; Email: VRolland-neyret@chu-grenoble.fr

Study Locations

• France
  • Grenoble, France, 38043
    • Recruiting
    • CHU de Grenoble Alpes
    • Contact: Sophie PARK; Phone Number: 04 76 76 27 77; Email: SPark@chu-grenoble.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with MDS according to WHO 2008 criteria (refractory anemia with multilineage dysplasia, RA (refractory anemia), refractory anemia with ringed sideroblasts (RARS) including CMML-1 (chronic myelomonocytic leukemia) type 1 with <10% blasts)
2. low risk (IPSS-R very low, low and intermediate)
3. in primary or secondary failure after erythropoiesis stimulating agents (ESAs), (either epoetins (≥60,000 units / week), or darbepoetin (≥250 μg / week), administered for at least 12 weeks, as defined by the IWG criteria 2006 (no erythroid response at 12 weeks, or more than 15g / l decrease in Hb after response to ESAs) PS: Patients with low transfusion of less than (<) 4RBP assessed over 4 months (RBP administered for patients with Hb ≤ 9g / dl) will be accepted)
4. age ≥ 18 years
5. ECOG ≤2
6. informed consent dated and signed
7. affiliated to a social security scheme
8. Women and men of childbearing potential must have effective contraception throughout the duration of the study and up to 4 days after the last administration of deferasirox

Exclusion Criteria:

1. Transfusion dependent patient (≥) 2 red blood cells (RBP) per 2-month period evaluated over 4 months between M-4 and M0
2. Patients with high-risk MDS (based on IPSS-R) and patients with other hematologic and non-haematological malignancies who should not benefit from chelation therapy due to rapid progression of their disease
3. Ferritin <200 ng / ml
4. Iron overload: ferritin> 1000 ng / ml
5. Creatinine clearance according to MDRD ≤60 ml / min
6. 5q- deletion to karyotype
7. Patient eligible for allograft
8. Patient participating in another interventional clinical study or exclusion period from another study
9. History of cancer treated or untreated for less than 5 years, whether or not there are signs of relapse or metastases, with the exception of basocellular cancers.
10. Persons referred to in Articles L1121-5 to L1121-8 of the CSP: pregnant woman, parturient, mother who is breastfeeding, person deprived of liberty by judicial or administrative decision, person subject to a legal protection measure, can not not be included in clinical trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Deferasirox; efficacy of 3.5mg/kg/day	Drug: Deferasirox; iron chelation; Other Names: exjade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients without transfusion-dependence at 12 months.	Percentage of patients without transfusion-dependence at 12 months.	12 months

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Collaborators: Novartis
• Investigators: Principal Investigator: Sophie Park, University Hospital, Grenoble

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2018
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: December 22, 2017
• First Submitted That Met QC Criteria: December 22, 2017
• First Posted (Actual): January 2, 2018

Study Record Updates

• Last Update Posted (Actual): May 20, 2022
• Last Update Submitted That Met QC Criteria: May 19, 2022
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: safety; efficacy
• Additional Relevant MeSH Terms: Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Preleukemia; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferasirox
• Other Study ID Numbers: 38RC17.064

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: e crf

Drug and device information, study documents

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