Assessment of Body, Liver and Labile Plasma Iron and Their Association With Outcome and Immunological Recovery in Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) Patients Undergoing Allogeneic Stem Cell Transplantation - ALLIVE (ALLogeneic Iron inVEstigators) Observational Trial (ALLIVE)

Assessment of Body, Liver and Labile Plasma Iron and Their Association With Outcome and Immunological Recovery in MDS or AML Patients Undergoing Allogeneic Stem Cell Transplantation - ALLIVE (ALLogeneic Iron inVEstigators) Observational Trial

The ALLIVE (ALLogeneic Iron inVEstigators) trial aims at quantifying the extent and dynamic change of LPI occurrence during conditioning and at identifying LPI-predictive peri-transplant parameters. Further points of interest are the improvement of systemic iron overload (SIO) diagnostics and the correlation of different SIO parameters with outcome after transplantation. The results of this trial will help to design prospective interventional studies addressing therapeutic options in patients at risk for SIO-associated toxicity during allogeneic stem-cell transplantation (allo-SCT).

Study Overview

• Status: Completed
• Conditions: MDS and AML Prior to Allogeneic SCT
• Intervention / Treatment: Other: No intervention and study treatment

• Study Type: Observational
• Enrollment (Actual): 134

Contacts and Locations

Study Locations

• Germany
  • Baden-Württemberg
    • Mannheim, Baden-Württemberg, Germany, 68167
      • III. Medizinischen Klinik Hämatologie und Internistische Onkologie Universitätsmedizin Mannheim
  • Bayern
    • München, Bayern, Germany, 81675
      • III. Medizinischen Klinik des Klinikums rechts der Isar
  • Hessen
    • Frankfurt, Hessen, Germany, 60590
      • Universitätsklinikum MKII, Hämatologie/Onkologie, Universitäres Zentrum für Tumorerkrankungen
  • Nordrhein-Westfalen
    • Bonn, Nordrhein-Westfalen, Germany, 53127
      • Medizinische Klinik und Poliklinik III Abteilung für Hämatologie und Onkologie Universitätsklinikum Bonn
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Universitätsklinikum Carl Gustav Carus der TU Dresden Medizinische Klinik und Poliklinik I

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Men and women with AML or MDS according to WHO classification.

Description

Inclusion Criteria:

• Age >= 18 years at the time of signing the informed consent form
• Signed informed consent
• Diagnosis of AML or MDS according to WHO classification
• Planned allogeneic stem cell transplantation after reduced intensity or myeloablative conditioning from related or unrelated donors
• At risk for iron toxicity as defined by ferritin >500 ng/ml and/or history of more than 10 RBC transfusions prior to allo-SCT

Exclusion Criteria:

• Claustrophobia or other mental disorders making MRI imaging unbearable for the patient
• Cardiac pacemakers, metal implants splinters or other contraindications for MRI
• More than 1 Human leukocyte antigen (HLA) allele or antigen mismatch between donor and recipient
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
• Patients with a history of chronic drug abuse or another illness which does not allow the patient to assess the nature and/or possible consequences of the study
• Patients who are not likely to follow the trial protocol (lack of willingness to cooperate)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with MDS and AML prior to allogeneic SCT	Other: No intervention and study treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Description of dynamic changes of LPI prior, during and after conditioning for allo-SCT using standard descriptive parameters (Mean or Median and appropriate confidence intervals)	one year

Secondary Outcome Measures

Outcome Measure	Time Frame
• Correlation coefficient of Liver iron concentration (LIC) and duration of detectable LPI during and after conditioning	one year
• Area under the Receiver-Operator-Characteristic (ROC) as well as sensitivity and specificity of specific thresholds of serum ferritin and transfusion history for prediction of LIC	one year
• Association of serum ferritin and LIC with hematopoietic cell transplantation comorbidity index (HCT-CI)	one year
• Time course of LPI, enhanced labile plasma iron (eLPI), directly chelatable iron (DCI) and hepcidin during allo-SCT	one year
• Association of detectable LPI or eLPI during conditioning and occurrence of elevated liver enzymes during in hospital treatment course for allo-SCT	one year
• Cumulative incidence of graft versus host disease (aGvHD) grade 2-4 with respect to serum ferritin >1000 µg/l, transfusion burden >20 units of Red blood cells (RBC), LIC >125 µmol/g, peak value and duration of detectable labile plasma iron above median	one year
• Cumulative incidence of day 100 non-relapse mortality (NRM) with respect to serum ferritin >1000 µg/l, transfusion burden >20 units of RBC, LIC >125 µmol/g and peak value and duration of detectable labile plasma iron above median	one year
• Cumulative incidence of infections with respect to serum ferritin >1000 µg/l, transfusion burden >20 parasitized red blood cell (PRBC), LIC >125 µmol/g and peak value and duration of detectable labile plasma iron above median	one year
• Median change of serum ferritin and LIC 100 days and 1 year after allo-SCT	one year
• Association between immune profile and iron parameters (serum ferritin >1000 µg/l, transfusion burden >20 units RBC, LIC >90 µmol/g and peak value and duration of detectable labile plasma iron above median	one year

Collaborators and Investigators

• Sponsor: GWT-TUD GmbH
• Investigators: Principal Investigator: Martin Wemke, MD, on behalf of GWT

Publications and helpful links

General Publications

• Wermke M, Eckoldt J, Gotze KS, Klein SA, Bug G, de Wreede LC, Kramer M, Stolzel F, von Bonin M, Schetelig J, Laniado M, Plodeck V, Hofmann WK, Ehninger G, Bornhauser M, Wolf D, Theurl I, Platzbecker U. Enhanced labile plasma iron and outcome in acute myeloid leukaemia and myelodysplastic syndrome after allogeneic haemopoietic cell transplantation (ALLIVE): a prospective, multicentre, observational trial. Lancet Haematol. 2018 May;5(5):e201-e210. doi: 10.1016/S2352-3026(18)30036-X. Epub 2018 Apr 5.

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: December 5, 2012
• First Submitted That Met QC Criteria: December 6, 2012
• First Posted (Estimate): December 10, 2012

Study Record Updates

• Last Update Posted (Estimate): December 13, 2016
• Last Update Submitted That Met QC Criteria: December 12, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: AML; MDS; allogeneic SCT
• Other Study ID Numbers: ALLIVE-2012