Post Hematopoietic Stem Cell Transplantation

A Phase II, Multi-center, Single-arm, Prospective Study to Evaluate the Safety and Efficacy of Deferasirox in Beta-thalassemia Major Patients After Hematopoietic Stem Cell Transplantation.

This was a prospective, single-arm, multicenter, national, phase II clinical study. The purpose of this Phase II study was to examine the safety and efficacy of deferasirox to decrease iron overload (IOL) in the posttransplant period in patients with beta-thalassemia major.

Study Overview

• Status: Completed
• Conditions: Iron Overload After Hematopoietic Stem Cell Transplantation (HSCT) in Patients With Beta-thalassemia Major
• Intervention / Treatment: Drug: ICL670

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 4

Contacts and Locations

Study Locations

• Turkey
  • Ankara, Turkey, 06100
    • Novartis Investigative Site
  • Ankara, Turkey, 06500
    • Novartis Investigative Site
  • Antalya, Turkey, 07070
    • Novartis Investigative Site
  • Antalya, Turkey, 07000
    • Novartis Investigative Site
  • Istanbul, Turkey
    • Novartis Investigative Site
  • Izmir, Turkey, 35040
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Patients who had hematopoietic stem cell transplantation (HSCT) for beta-thalassemia major
• hematopoietic stem cell transplantation (HSCT) was performed minimum 6 months and maximum 2 years ago
• The washout period after the immunosuppressive therapy should be at least 3 months.
• Signifacant IOL should be present including:

A. Serum ferritin >1000 μg/L or B. cardiac MRI <20 ms or C. liver iron concentration ≥ 5 mg/g dry weight measured by R2* MRI

Exclusion Criteria

• Patients who had any contraindication for treatment with deferasirox according to the prescribing information

  •Patients who depended on transfusion

• Patients with clinical symptoms of cardiac dysfunction (shortness of breath at rest or exertion, orthopnea, exercise intolerance, lower extremity edema, arrhythmias)
• Patients who were experiencing severe complication of HSCT e.g. acute Graft-versus host disease (GVHD)
• Significant proteinuria / Increase in serum creatinine

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: ICL670; Oral dose of ICL670 at 10 mg/kg daily	Drug: ICL670; Oral dose of ICL670 at 10 mg/kg daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events, Serious Adverse Events and Deaths as a Measure of Safety and Tolerability	To determine the safety; incidence, type and severity of adverse events including renal, hepatic, biochemistry and hematologic parameters of deferasirox in the treatment of iron overload after hematopoietic stem cell transplantation (HSCT) in patients with beta-thalassemia major in 12 months period	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Serum Ferritin Level.	Blood samples were collected and serum levels were assessed at study baseline (BL) and at 12 months.	Baseline, 12 Months
Change in the Further Parameters of Iron Overload (Liver Iron Concentration by Magnetic Resonance Imaging (MRI Examination)	Liver Iron Concentration (LIC) values between 3 and 7 mg Fe / g dry weight are indicative of mild iron deposition, while values between 7 and 15 mg Fe / g dry weight are indicative of moderate iron deposition which have been associated with liver disease. Values >15 mg Fe/g dry weight are indicative of severe iron deposition which is associated with progressive liver fibrosis, increased morbidity and mortality	Baseline, 12 month
The Percentage of Patients Reaching Serum Ferritin Levels Lower Than 500 μg/L	Serum Ferritin values between 1000-2500 μg/L are indicative of mild to moderate iron overload while values >2500 μg/L are indicative of severe iron overload and levels constantly higher than 2500 μg/L has been shown to to increase the risk of cardiac complications and endocrine disease. Maintaining levels <1000 μg/L is associated with increased survival and less morbidity.	Week 28 and Week 52
Change in the Further Parameters of Iron Overload (Cardiac Iron Concentration by Magnetic Resonance Imaging (MRI Examination)	Cardiac MRI values between 10 to 20 milliseconds (ms) are indicative of moderate cardiac iron deposition associated with declining left ventricular ejection fraction and arrhythmias while values <10 ms are indicative of deposition sufficient to risk cardiac decompensation and associated with overt heart failure and mortality.	Baseline, 12 month

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Yesilipek MA, Karasu G, Kaya Z, Kuskonmaz BB, Uygun V, Dag I, Ozudogru O, Ertem M. A Phase II, Multicenter, Single-Arm Study to Evaluate the Safety and Efficacy of Deferasirox after Hematopoietic Stem Cell Transplantation in Children with beta-Thalassemia Major. Biol Blood Marrow Transplant. 2018 Mar;24(3):613-618. doi: 10.1016/j.bbmt.2017.11.006. Epub 2017 Nov 16.

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: May 30, 2012
• First Submitted That Met QC Criteria: June 1, 2012
• First Posted (Estimate): June 4, 2012

Study Record Updates

• Last Update Posted (Estimate): October 24, 2016
• Last Update Submitted That Met QC Criteria: September 12, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: hematopoietic stem cell transplantation, beta-thalassemia major, deferasirox, iron overload
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Iron Metabolism Disorders; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Iron Overload; Thalassemia; beta-Thalassemia; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferasirox
• Other Study ID Numbers: CICL670ATR04