Study Of Efficacy,Safety of Combined Deferasirox and Deferiprone Versus Combined Deferiprone and Desferal In Conditions of Iron Overload

NCT01511848 | Unknown Phase 2 DMC

• 1 other identifier: AinShamsU
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Interventional Allocation: Randomized Endpoint Classification: Safety/Efficacy Study of combined chelation therapy Masking: Open Label Primary Purpose: Treatment of transfusional iron overload Primary Outcome Measures:

• The primary outcome measure is to assess efficacy in lowering serum ferritin level(the change in serum ferritin compared to baseline) with combining DFP and deferasirox compared to combined DFP and DFO in conditions with severe chronic iron overload; showing an up-trend of SF over previous 12 months on single chelator. Secondary Outcome Measures:
• The secondary outcome measure is to determine the number of patients who will develop adverse events in order to assess safety upon administering the drugs in combination (DFP and DFX) compared to the combination of DFO and DFP.

Conditions

Beta-thalassemia Major; Sickle Cell Disease; Iron Hemosiderosis

Keywords

Iron chelation; Iron balance; Secondary iron overload; deferoxamine; deferasirox; Deferiprone; 1- Beta-thalassemia major patients;; Patients with high iron stores; Serum ferritin consistently > 2500 mcg/l and or increasing trend over previous 12 months; Liver iron >14 mg/g dry weight- by R2 MRI; 2- Sickle cell disease; 3- Other causes of transfusional iron hemosiderosis

Outcome Measures

Primary Outcomes (1)

• to assess efficacy of combining DFP and deferasirox compared to combined DFP and DFO in decreasing the serum ferritin level in conditions with severe chronic iron overload.

  • The primary outcome measure is to measure the change in serum ferritin level from baseline in the 2 combination therapy.

  12 months

Secondary Outcomes (1)

• to determine the safety upon administering the drugs in combination (DFP and DFX) compared to the combination of DFO and DFP.

  12 months

Study Arms (2)

arm 1

ACTIVE COMPARATOR

30 Patients will be treated with combined DFP and deferasirox.

Drug: DFP (ferriprox) and deferasirox (ICL 670)

arm 2

ACTIVE COMPARATOR

Patients will be treated for 6 days with a combination of deferoxamine and DFP

Drug: DFP, DFO

Interventions

DFP (ferriprox) and deferasirox (ICL 670) DRUG

Drug: Ferriprox It will be given orally in the morning Other Name: DFP Initial dose 25/mg/kg 3 times/d (better tolerated if started and then built up over 4 weeks). Dose may be increased up to 100mg/kg/day guided by serum ferritin. Agranulocytosis risk 1-2%. Monitor TLC and granulocytic count / 2weeks. Patients need to be continually educated about this risk, know that they must stop DFP if they have a fever or infection. Drug: Deferasirox will be orally administered at a dose of 20 mg/kg once daily at evening for 5 days. Other Name: ICL670

arm 1

DFP, DFO DRUG

Drug: Deferoxamine It will be administered subcutaneously over 8 hours for 5 days at a dose of 40 mg/kg. Other Name: Desferal, DFO Drug: DFP DFP: will be orally administered at a dose of 75mg/kg orally in 3 divided doses for 7 days

arm 2

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subjects with transfusional iron overload secondary to thalassemia major , sickle cell disease showing up-trend in SF aged 6 Years or older, may participate after Approval of Ethical committee giving written informed consent.
• Subjects must have a serum ferritin greater than \>2500 ng/mL, a platelet count greater than 100,000/mm3, and a serum creatinine within the normal range.
• A woman of childbearing potential must have a negative serum pregnancy test at screening. She must use a medically acceptable form of birth control during the study and for 1 month afterward.
• The subjects must also have a level of understanding and willingness to cooperate with the confinement and procedures described in the consent form and scheduled by the study site. In addition, he/she must be able to provide voluntary written informed consent.

You may not qualify if:

• Subjects with a past history of agranulocytosis, history of clinically significant gastrointestinal, renal, hepatic ALT \> 10 times high normal, OR \> 50% increase of serum creatinine from basal value, pulmonary or cardiovascular disease. Patients with a history of tuberculosis, epilepsy, psychosis, glaucoma or any other condition, which in the opinion of the investigators, would jeopardize the safety of the subject or impact the validity of the study results.
• Subjects with HIV positive or have active HCV.
• A history of serious immunologic hypersensitivity to any medication, such as anaphylaxis or angioedema.
• Participation in a previous investigational drug study within the 30 days preceding screening..
• Women who are pregnant, or breast-feeding.
• Current alcohol or drug abuse.
• An inability to adhere to the designated procedures and restrictions of this protocol.
• Subjects receiving warfarin, digoxin, or anti-arrhythmic or anti-seizure medications.
• Subjects with a known allergy to Exjade or DFP that prevents chronic administration.

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Pediatric Hematology clinic, Ain Shams University

Cairo, Egypt

Location

Related Publications (1)

• Elalfy MS, Adly AM, Wali Y, Tony S, Samir A, Elhenawy YI. Efficacy and safety of a novel combination of two oral chelators deferasirox/deferiprone over deferoxamine/deferiprone in severely iron overloaded young beta thalassemia major patients. Eur J Haematol. 2015 Nov;95(5):411-20. doi: 10.1111/ejh.12507. Epub 2015 Mar 27.

  PMID: 25600572 DERIVED

MeSH Terms

Conditions

beta-Thalassemia; Anemia, Sickle Cell

Interventions

Isoflurophate; Deferiprone; Deferasirox; Deferoxamine

Condition Hierarchy (Ancestors)

Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Organofluorophosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Pyridones; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Hydroxamic Acids; Hydroxylamines; Amines; Hydroxy Acids

Study Officials

• Mohsen S. Elalfy, professour

  Ain Shams University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amira A M Adly, Asst. prof.

CONTACT

0105245837; amiradiabetes@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professour of pediatrics

Study Record Dates

• First Submitted: January 6, 2012
• First Posted: January 19, 2012
• Study Start: February 1, 2012
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: February 6, 2012

Record last verified: 2012-02

Locations

EG (1)