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

NCT01868477 | Completed Phase 2 Results

• 1 other identifier: CICL670A2421
• Study Type: interventional
• Target: 28
• Locations: 10 countries
• Sites: 30

Brief Summary

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.

Conditions

Low and Int 1-risk Myelodysplastic Syndrome

Keywords

myelodysplastic syndrome; MDS; myelodysplasia; blood disorder; cytopenias; low blood counts; progressive bone marrow failure; adult; ICL570; deferasirox; erythropoietin; erythropoiesis; NF-kB pathway; hematopoiesis.

Outcome Measures

Primary Outcomes (1)

• Difference in Percentage of Patients Achieving Erythroid Response Within 12 Weeks, by Treatment Group (Full Analysis Set)

  Difference in percentage of patients achieving an erythroid response within 12 weeks of treatment between the two arms according to modified IWG 2006 criteria increase in hemoglobin (Hb) ≥ 1.5 g/dL. Erythroid response is defined as the increase in Hb from baseline ≥ 1.5 g/dL. Patients achieving erythroid response at least once within 12 weeks were considered responders

  Baseline up to 12 weeks

Secondary Outcomes (12)

• Absolute Change From Baseline to Post-baseline Value for Hemoglobin(g/dL)(Full Analysis Set)

  Baseline up to 24 weeks

• Summary of Hematologic Improvement in Patients Randomized to EPO+DFX and EPO Alone, Within 24 Weeks of Treatment (Full Analysis Set)

  Baseline up to 24 weeks

• Absolute Change in Hemoglobin Values up to 24 Weeks

  Baseline up to 24 weeks

• Absolute Change in Platelets and Neutrophil Levels up to 24 Weeks

  Baseline up to 24 weeks

• Summary of Erythroid Response in Participants Randomized to EPO Alone at Baseline and Switched to EPO+DFX After 12 Weeks of Treatment (Full Analysis Set)

  Week 13 up to 24 weeks

Study Arms (2)

Erythropoietin alpha

EXPERIMENTAL

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.

Drug: Erythropoietin alpha

Deferasirox + Erythropoietin alpha

EXPERIMENTAL

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.

Drug: Deferasirox DFX, DT; Drug: Deferasirox DFX, FCT

Interventions

Deferasirox DFX, DT DRUG

provided as dispersible tablets for oral use in 125 and 250, 500 mg

Deferasirox + Erythropoietin alpha

Erythropoietin alpha DRUG

Erythropoietin alpha

Deferasirox DFX, FCT DRUG

provided as film-coated tablet for oral use in 90, 180, 360 mg strengths

Deferasirox + Erythropoietin alpha

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (30)

Novartis Investigative Site

Oran, 31000, Algeria

Location

Novartis Investigative Site

Sidi Bel Abbes, 22000, Algeria

Location

Novartis Investigative Site

CABA, Buenos Aires, C1425DND, Argentina

Location

Novartis Investigative Site

La Plata, Buenos Aires, B1900AWT, Argentina

Location

Novartis Investigative Site

Vancouver, British Columbia, V6Z1Y6, Canada

Location

Novartis Investigative Site

Hamilton, Ontario, L8V 5C2, Canada

Location

Novartis Investigative Site

Toronto, Ontario, M4N 3M5, Canada

Location

Novartis Investigative Site

Beijing, Beijing Municipality, 100730, China

Location

Novartis Investigative Site

Guangzhou, Guangdong, 51000, China

Location

Novartis Investigative Site

Nanjing, Jiangsu, China

Location

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

Location

Novartis Investigative Site

Hangzhou, Zhejiang, 310003, China

Location

Novartis Investigative Site

Shanghai, 200025, China

Location

Novartis Investigative Site

Berlin, 12203, Germany

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Düsseldorf, 40225, Germany

Location

Novartis Investigative Site

Lütten Klein, 18107, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

Novartis Investigative Site

Cagliari, CA, 09126, Italy

Location

Novartis Investigative Site

Reggio Calabria, RC, 89124, Italy

Location

Novartis Investigative Site

Roma, RM, 00161, Italy

Location

Novartis Investigative Site

Seoul, Korea, 06351, South Korea

Location

Novartis Investigative Site

Badalona, Catalonia, 08916, Spain

Location

Novartis Investigative Site

Girona, Catalonia, 17007, Spain

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

Location

Novartis Investigative Site

Gothenburg, 413 45, Sweden

Location

Novartis Investigative Site

Linköping, SE-581 85, Sweden

Location

Novartis Investigative Site

Luleå, SE 971 80, Sweden

Location

Novartis Investigative Site

Stockholm, SE-141 86, Sweden

Location

Novartis Investigative Site

Oldham, Lancashire, OL1 2JH, United Kingdom

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts; Hematologic Diseases; Cytopenia

Interventions

Deferasirox; Epoetin Alfa

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hemic and Lymphatic Diseases; Anemia, Refractory; Anemia

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2013
• First Posted: June 4, 2013
• Study Start: January 28, 2014
• Primary Completion: March 22, 2017
• Study Completion: April 5, 2017
• Last Updated: October 31, 2018
• Results First Posted: October 31, 2018

Record last verified: 2018-10

Locations

DE (5); SE (4); AR (2); ES (3); GB (1); AL (2); CA (3); IT (3); KR (1); CN (6)