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)

• ClinicalTrials.gov Identifier: NCT01746147
• Recruitment Status: Completed
• First Posted: December 10, 2012
• Last Update Posted: December 13, 2016
• Sponsor: GWT-TUD GmbH
• Information provided by (Responsible Party): GWT-TUD GmbH

Tracking Information

• First Submitted Date: December 5, 2012
• First Posted Date: December 10, 2012
• Last Update Posted Date: December 13, 2016
• Study Start Date: December 2012
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 6, 2012): 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) [ Time Frame: one year ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 10, 2012)

• • Correlation coefficient of Liver iron concentration (LIC) and duration of detectable LPI during and after conditioning [ Time Frame: 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 [ Time Frame: one year ]
• • Association of serum ferritin and LIC with hematopoietic cell transplantation comorbidity index (HCT-CI) [ Time Frame: one year ]
• • Time course of LPI, enhanced labile plasma iron (eLPI), directly chelatable iron (DCI) and hepcidin during allo-SCT [ Time Frame: one year ]
• • Association of detectable LPI or eLPI during conditioning and occurrence of elevated liver enzymes during in hospital treatment course for allo-SCT [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: one year ]
• • Median change of serum ferritin and LIC 100 days and 1 year after allo-SCT [ Time Frame: 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 [ Time Frame: one year ]

Original Secondary Outcome Measures (submitted: December 6, 2012)

• • Correlation coefficient of LIC and duration of detectable LPI during and after conditioning [ Time Frame: 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 [ Time Frame: one year ]
• • Association of serum ferritin and LIC with hematopoietic cell transplantation comorbidity index (HCT-CI) [ Time Frame: one year ]
• • Time course of LPI, enhanced labile plasma iron (eLPI), directly chelatable iron (DCI) and hepcidin during allo-SCT [ Time Frame: one year ]
• • Association of detectable LPI or eLPI during conditioning and occurrence of elevated liver enzymes during in hospital treatment course for allo-SCT [ Time Frame: one year ]
• • Cumulative incidence of aGvHD grade 2-4 with respect to serum ferritin >1000 µg/l, transfusion burden >20 units of RBC, LIC >125 µmol/g, peak value and duration of detectable labile plasma iron above median [ Time Frame: one year ]
• • Cumulative incidence of day 100 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 [ Time Frame: one year ]
• • Cumulative incidence of infections with respect to serum ferritin >1000 µg/l, transfusion burden >20 PRBC, LIC >125 µmol/g and peak value and duration of detectable labile plasma iron above median [ Time Frame: one year ]
• • Median change of serum ferritin and LIC 100 days and 1 year after allo-SCT [ Time Frame: 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 [ Time Frame: one year ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: 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
• Brief Summary: 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).
• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Case-Only; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Men and women with AML or MDS according to WHO classification.
• Condition: MDS and AML Prior to Allogeneic SCT
• Intervention: Other: No intervention and study treatment

Study Groups/Cohorts

Patients with MDS and AML prior to allogeneic SCT

Intervention: Other: No intervention and study treatment

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 6, 2012): 134
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 2016
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT01746147
• Other Study ID Numbers: ALLIVE-2012
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: GWT-TUD GmbH
• Original Responsible Party: Same as current
• Current Study Sponsor: GWT-TUD GmbH
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Martin Wemke, MD; on behalf of GWT

• PRS Account: GWT-TUD GmbH
• Verification Date: December 2016