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

Myelodysplasia Clinical Trial

— LODEFI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03387475
• Other study ID #: 38RC17.064
• Status: Recruiting
• Phase: Phase 2
• Start date: February 20, 2018
• Est. completion date: December 31, 2024

Study information

• Verified date: September 2021
• Source: University Hospital, Grenoble
• Contact: Sophie Park
• Phone: 0476762777
• Email: Spark[@]chu-grenoble.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 39
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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.

Related Conditions & MeSH terms

• Myelodysplasia
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• Deferasirox
iron chelation

Locations

Country	Name	City	State
France	CHU de GRENOBLE ALPES	Grenoble

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Grenoble	Novartis

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients without transfusion-dependence at 12 months.	Percentage of patients without transfusion-dependence at 12 months.	12 months