Deferasirox in Treating Patients With Iron Overload After Undergoing a Donor Stem Cell Transplant

Open-Label Single-Arm Pilot Study of Deferasirox (Exjade®) in Adult Allogeneic Hematopoietic Stem Cell Transplant Recipients With Transfusional Iron Overload

RATIONALE: Deferasirox may be effective in treating iron overload caused by blood transfusions in patients who have undergone donor stem cell transplant.

PURPOSE: This phase II trial is studying the side effects and how well deferasirox works in treating patients with iron overload after donor stem cell transplant.

Study Overview

• Status: Terminated
• Conditions: Lymphoma; Myelodysplastic Syndromes; Leukemia; Breast Cancer; Iron Overload; Ovarian Cancer; Neuroblastoma; Multiple Myeloma and Plasma Cell Neoplasm
• Intervention / Treatment: Drug: deferasirox

Detailed Description

OBJECTIVES:

Primary

• To evaluate the safety of deferasirox given over 6 months in reducing liver iron concentration in patients with transfusional iron overload after undergoing allogeneic hematopoietic stem cell transplantation.

Secondary

• To evaluate the efficacy of deferasirox in reducing liver iron overload in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral deferasirox once daily for 6 months in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed at 4 weeks.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center at University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed diagnosis of iron overload, defined as serum ferritin > 1,000 ng/mL and liver iron concentration ≥ 5 mg iron/g on tissue proton transverse relaxation rates Magnetic Resonance Imaging (MRI)
• Underwent prior allogeneic hematopoietic stem cell transplantation (HSCT) using either myeloablative or reduced-intensity conditioning at least 12 months ago
• No evidence of relapse or progression of the primary disease for which allogeneic HSCT was performed
• Patients who have become red-cell transfusion independent (i.e., no red cell transfusions within the past 3 months) as well as patients who require red cell transfusions are eligible

• Meets one of the following criteria:

  • Ineligible for phlebotomy (hemoglobin < 11 g/dL, poor intravenous access, or unable to undergo phlebotomy every 4 weeks)
  • Have failed treatment with phlebotomy (serum ferritin > 50% of baseline after 3 months of phlebotomy)
  • Refused phlebotomy
• ECOG performance status of 0-2
• Life expectancy ≥ 6 months
• Adequate renal function defined as serum creatinine < or = 1.6 mg/dL and creatinine clearance of > or = 60 ml/min calculated using the Crockcroft-Gault formula on 2 occasions within 30 days of enrollment
• Sexually active men and women must use an effective method of contraception. Alternatively, women must have undergone clinically documented total hysterectomy and/or oophorectomy, or tubal ligation or be postmenopausal.
• Must be able to give written informed consent.
• Prior therapy with deferoxamine allowed provided it was completed ≥ 12 months ago

Exclusion Criteria:

• Contraindication for performing MRI or inability to undergo MRI because of claustrophobia or weight (>350 pounds).
• Inability to take medications orally.
• Uncontrolled bacterial, viral, or fungal infection
• ANC ≥ 1,000/mm³
• Hemoglobin ≥ 8.0 g/dL
• Platelet count ≥ 50,000/mm³
• Aspartate aminotransferance (AST) and alanine aminotransferase (ALT) ≤ 5 times the upper limit of normal
• Less than 4 weeks since prior and no concurrent systemic investigational drug
• Less than 7 days since prior and no concurrent topical investigational drug. Concurrent non-investigational medications needed to treat concomitant medical conditions are allowed, with the exception of other chelating agents. Concurrent growth factors such as epoetin alfa, darbepoetin alfa, filgrastim (G-CSF), and sargramostim (GM-CSF) allowed. Concurrent irradiated packed red-cell and platelet transfusions allowed as clinically indicated. Concurrent low-doses of vitamin C supplements (≤ 200 mg/day) allowed.
• Concurrent iron supplements or multivitamins with iron.
• Aluminum-containing antacid therapies may not be taken simultaneously with deferasirox, but may be taken 2 hours before or after administration of deferasirox
• On dialysis or status post-renal transplantation
• Pregnant or nursing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Deferasirox Treated; Includes patients that were treated with deferasirox for 6 months.	Drug: deferasirox; 20 mg/kg once daily orally for 6 months; Other Names: Exjade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients Not Completing Treatment	Number of patients who discontinued deferasirox during 6 month daily treatment due to drug related toxicity	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in Liver Iron Concentration After Study Drug	Efficacy as measured by reduction in liver iron concentration (LIC) after 6 months of the study drug compared to baseline (LIC at baseline minus LIC at 6 months). This shows the mean reduction for the 3 subjects treated in this study.	6 Months

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Investigators: Principal Investigator: Linda J. Burns, MD, Masonic Cancer Center, University of Minnesota

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: January 24, 2008
• First Submitted That Met QC Criteria: January 24, 2008
• First Posted (Estimate): January 28, 2008

Study Record Updates

• Last Update Posted (Actual): December 28, 2017
• Last Update Submitted That Met QC Criteria: December 3, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: iron overload
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Glandular and Epithelial; Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Iron Metabolism Disorders; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Myelodysplastic Syndromes; Multiple Myeloma; Neoplasms, Plasma Cell; Iron Overload; Neuroblastoma; Plasmacytoma; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferasirox
• Other Study ID Numbers: CDR0000584690; UMN-2007LS065 (Other Identifier: Masonic Cancer Center, University of Minnesota); UMN-MT2007-11R (Other Identifier: Blood and Marrow Transplantation Program); NOVARTIS-CICL670AUS12 (Other Identifier: Novartis Pharmaceuticals)