Iron Overload in Patients Undergoing Donor Stem Cell Transplant

Iron Overload in Allogeneic Hematopoietic Cell Transplantation

RATIONALE: Learning about the effect of excess iron in the liver of patients undergoing donor stem cell transplant may help doctors plan treatment.

PURPOSE: This study is investigating the effects of iron overload in patients undergoing donor stem cell transplant.

Study Overview

• Status: Completed
• Conditions: Cancer; Hematopoietic Stem Cell Transplantation; Allogeneic Hematopoietic Cell Transplantation
• Intervention / Treatment: Procedure: magnetic resonance imaging; Procedure: Serum ferritin

Detailed Description

OBJECTIVES:

Primary

• Determine the impact of pre-transplant iron overload (defined as liver iron concentration [LIC] above normal [> 1.8 mg/g] on an MRI of the liver measuring tissue proton transverse relaxation rates [R2 MRI]) on the probability of 1-year overall survival of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT).

Secondary

• Determine the impact of pre-transplant iron overload on the composite endpoint of non-relapse mortality and complications (e.g., serious infections, hepatic veno-occlusive disease, or organ failure) within 1 year after allogeneic HSCT.
• Determine the impact of pre-transplant iron overload on the 1-year cumulative incidence of acute or chronic graft-vs-host disease in patients with acute leukemia or myelodysplastic syndromes undergoing allogeneic HSCT.
• Determine the impact of pre-transplant iron overload on the 1-year probability of overall survival and non-relapse mortality in patients undergoing allogeneic HSCT.
• Determine the prevalence of pre-transplant iron overload in adult patients undergoing allogeneic HSCT.
• Determine the correlation between pre-transplant ferritin levels and LIC on R2 MRI.
• Compare the longitudinal measures of serum ferritin levels after allogeneic HSCT in patients with iron overload vs those without iron overload.
• Estimate the cumulative incidence of iron overload at 1 year after allogeneic HSCT.

OUTLINE: Patients undergo blood sample collection to measure serum ferritin levels at baseline (pre-transplant) and then at 3, 6, 9, and 12 months after transplant. Patients with serum ferritin > 500 ng/mL also undergo an R2 MRI at baseline (pre-transplant) and at 12 months after transplant to determine liver iron concentration. Patients with serum ferritin > 500 ng/mL at 12 months after transplant also undergo an R2 MRI.

• Study Type: Observational
• Enrollment (Actual): 112

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Children's Hospital - Fairview

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Allogeneic Hematopoietic Cell Transplantation

Description

Inclusion Criteria:

• Planning to undergo allogeneic hematopoietic stem cell transplantation using either myeloablative or reduced-intensity conditioning

  • Any diagnosis allowed
• Not pregnant
• Weight ≤ 350 lbs
• Must be able to give written informed consent indicating the investigational nature of the study and its potential risks.

Exclusion Criteria:

• Claustrophobia
• Other contraindication for MRI (e.g., cardiac pacemaker, implanted cardiac defibrillator, aneurysm clips, carotid artery vascular clamp, neurostimulator, insulin or infusion pump, or implanted drug infusion device)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Without Iron Overload; Patients entering study without pre-HSCT iron-overload. Iron overload will be defined as liver ion concentration (LIC above normal (>1.8 mg/g) on R2 magnetic resonance imaging (MRI) of the liver.	Procedure: magnetic resonance imaging; MRI of the liver will be performed within 30 days prior to HSCT (day 0) and can be done during receipt of conditioning regimen chemotherapy and/or radiation therapy. MRI will also be performed in selected patients at 1 year post-HSCT. This MRI will be done within ± 30 days of their 1-year post-transplant followup date. The R2 MRI is a specific MRI technique and cannot be used for the purpose of general diagnostic imaging. In our study, this modality is being used specifically for the estimation of LIC.; Other Names: R2 MRI; Procedure: Serum ferritin; Blood samples will be taken pre-transplant, 3, 6, 9 and 12 months post-transplant
With Iron-Overload; Patients entering study with pre-HSCT iron-overload. Iron overload will be defined as liver ion concentration (LIC above normal (>1.8 mg/g) on R2 magnetic resonance imaging (MRI) of the liver.	Procedure: magnetic resonance imaging; MRI of the liver will be performed within 30 days prior to HSCT (day 0) and can be done during receipt of conditioning regimen chemotherapy and/or radiation therapy. MRI will also be performed in selected patients at 1 year post-HSCT. This MRI will be done within ± 30 days of their 1-year post-transplant followup date. The R2 MRI is a specific MRI technique and cannot be used for the purpose of general diagnostic imaging. In our study, this modality is being used specifically for the estimation of LIC.; Other Names: R2 MRI; Procedure: Serum ferritin; Blood samples will be taken pre-transplant, 3, 6, 9 and 12 months post-transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Number of patients alive at 1 year.	1 Year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of non-relapse mortality	Number of patients who died due to serious infections, hepatic venous occlusive disorder (VOD) or organ failure within one year of transplant.	Up to 1 Year
Acute and chronic graft-vs-host disease	Number of patients who had acute and chronic graft versus host disease through 1 year after transplant.	1 Year Post Transplant
Overall survival and non-relapse mortality	Number of patients who were alive and did not have any non-relapse mortality events at 1 year post transplant. Determine the impact of pre-transplant iron-overload on 1-year probability of overall survival and of non-relapse mortality in allogeneic HSCT recipients with acute leukemia and myelodysplastic syndrome.	1 Year Post Transplant
Number of Patients with Iron Overload	Prevalence of iron overload in patients being considered for allogeneic HSCT	Baseline
Ferritin levels and Liver Iron Concentration	Correlation between pre-transplant and post-transplant ferritin levels and liver iron concentration on an MRI of the liver measuring tissue proton transverse relaxation rates (R2 MRI)	Baseline, and 3, 6, 9, and 12 Months Post Transplant
Longitudinal averages of serum ferritin levels	Compare the longitudinal measures of serum ferritin between the no iron-overload and iron-overload groups.	Post Transplant
Incidence of iron overload	Compare the longitudinal measures of serum ferritin between the no iron-overload and iron-overload groups.	1 Year Post Transplant

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (ACTUAL): June 1, 2012
• Study Completion (ACTUAL): June 1, 2012

Study Registration Dates

• First Submitted: April 24, 2009
• First Submitted That Met QC Criteria: April 24, 2009
• First Posted (ESTIMATE): April 27, 2009

Study Record Updates

• Last Update Posted (ACTUAL): December 2, 2017
• Last Update Submitted That Met QC Criteria: November 29, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: iron overload
• Additional Relevant MeSH Terms: Metabolic Diseases; Iron Metabolism Disorders; Iron Overload
• Other Study ID Numbers: 2008NTLS103; 0807M41481 (OTHER: IRB, University of Minnesota); CICL670AUS28T (OTHER: Novartis Pharmaceuticals)