Combination Study of Deferasirox and Erythropoietin in Patients With Low- and Int-1-risk Myelodysplastic Syndrome.

Novartis

Status and phase: Completed; Phase 2

Conditions: Low and Int 1-risk Myelodysplastic Syndrome

Treatments: Drug: Erythropoietin alpha; Drug: Deferasirox DFX, DT; Drug: Deferasirox DFX, FCT

Study type: Interventional

Funder types: Industry

Identifiers

NCT01868477

CICL670A2421

Details and patient eligibility

About

The primary purpose of this trial was is to assess the effect of treatment with deferasirox combined with erythropoietin vs. erythropoietin alone on erythropoiesis in patients with low- and int-1-risk myelodysplastic syndrome. The addition of deferasirox to erythropoietin can lead to a potential synergism with the reduction of reactive oxygen species, through both the NF-kB pathway and the control of free toxic iron. This may create a better environment in the bone marrow for a better response with erythropoietin.

This study was designed to test in a prospective way the combination of deferasirox with erythropoietin in terms of their effect on hematopoiesis.

Full description

This study did not meet the original enrollment objective of 60 patients and was terminated without extending enrollment past original planned LPFV of 31-Oct-2016.

Enrollment: 28 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Patients who had low- and Int-1-risk myelodysplastic syndrome
• Documented diagnosis of the following:

Myelodysplastic syndrome that lasted ≥ 3 months and < 3 years Disease must not have been secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases

• A hemoglobin < 10 g/dL and ≥ 8 g/dL
• History of transfusions < 10 RBC units and must not have been RBC transfusion dependent
• 300 ng/mL < serum ferritin < 1,500 ng/mL (Values within 10% difference above 1500 ng/ml or 10% difference below 300 ng/ml could have been accepted at the investigator's discretion.
• Endogenous erythropoietin levels < 500 units/L
• Serum creatinine ≤ 1.5 times upper limit of normal (ULN)
• Creatinine clearance above the concentration limit in locally approved prescribing information (PI). Patients with creatinine clearance between 40 and less than 60 mL/min, who did not present with additional risk factors that might impair renal function, were eligible at the discretion of the investigator

Key Exclusion Criteria:

• Patients who had MDS with isolated del(5q)
• Patients who had received prior EPO treatment or other recombinant growth factors regardless of the outcome (Patient who had received prior EPO treatment or other recombinant growth factors for less than 4 weeks and not within 3 months before screening without a documented response are allowed)
• Patients who had received steroids or immunosuppressive therapy for the improvement of hematological parameters (stable steroid treatment for adrenal failure or chronic medical conditions, and intermittent dexamethasone as antiemetics were allowed).
• B12 and folate deficient patients with and without clinical symptoms (patients were rescreened after successful therapy of B12 and folate deficiency)
• Uncontrolled seizures or uncontrolled hypertension

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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28 participants in 2 patient groups

Erythropoietin alpha

Experimental group

Description:

Patients will receive erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement is inadequate, dose will be escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement in inadequate, patients will be switched to the combination arm. At any time when erythroid response is achieved, erythropoietin treatment will be stopped until end of study.

Treatment:

Drug: Erythropoietin alpha

Deferasirox + Erythropoietin alpha

Experimental group

Description:

Patients will receive deferasirox dispersible tablet (DT) 10 mg/kg/day or deferasirox film-coated tablet (FCT) 7 mg/kg/day in combination with erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement is inadequate, erythropoietin dose will be escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement in inadequate, patients will be discontinued from the study. At any time when erythroid response is achieved, erythropoietin treatment will be stopped until end of study. Patients will continue deferasirox treatment.

Treatment:

Drug: Deferasirox DFX, FCT

Drug: Deferasirox DFX, DT