Imaging of Chemotherapy-induced Morphological and Functional Lung Changes in Childhood ALL and HD (MinimALL)

iMagINg of Chemotherapy-Induced Morphological and Functional Lung Changes in Childhood Acute Lymphoblastic Leukemia and Hodgkin's Disease

With increasing cure rates of childhood cancer there is growing recognition of late effects of treatments. However, there is a lack of non-invasive and child-friendly procedures that can indicate possible late damage. This study uses morphologic and free-breathing phase-resolved functional low-field (PREFUL) magnetic resonance imaging (MRI) to identify persistent pulmonary toxicity after treatment for childhood acute lymphoblastic leukemia (ALL), Hodgkin's disease (HD) and allogeneic stem cell transplantation. Furthermore, cardiopulmonary testing is performed by means of a pulmonary function test, echocardiography with strain analysis and spiroergometry.

Study Overview

• Status: Recruiting
• Conditions: Hodgkin Disease; Acute Lymphoblastic Leukemia; Allogeneic Stem Cell Transplantation
• Intervention / Treatment: Diagnostic test: Low-field magnetic resonance imaging; Diagnostic test: Cardiopulmonary testing; Diagnostic test: Pulmonary testing; Diagnostic test: Blood sample

Detailed Description

With increasing cure rates of childhood cancer there is growing recognition of late effects of treatments. However, there is a lack of non-invasive and child-friendly procedures that can indicate possible late damage.

This study uses morphologic and free-breathing phase-resolved functional low-field (PREFUL) magnetic resonance imaging (MRI) to identify persistent pulmonary toxicity after treatment for childhood acute lymphoblastic leukemia (ALL), Hodgkin's disease (HD) and allogeneic stem cell transplantation. The examination in the new 0.55 T MRI system does not differ in procedure and especially with regard to contraindications for an MRI examination from an examination in routinely used 1.5 or 3T devices. There is no intravenous administration of contrast medium. This method has already yielded relevant results in a previous study on the frequency of lung parenchymal changes in pediatric and adolescent patients with past SARS-CoV-2 infection detected by PCR. In addition, study participants will undergo cardiopilmonary testing by spirometry, spiroergometry and echocardiography with strain analysis to assess cardiac and pulmonary performance. For the individual patient, the duration of study participation is 120 minutes. This includes approximately 30 minutes for education and consent of study participants/parents/guardians, 30 minutes for lung function test and MRI, and 30 minutes for cardiopulmonary testing.

The purpose of this study is to assess early posttherapeutic changes as well as possible persistent pulmonary toxicity and change in cardiopulmonary performance.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Axel Karow, MD; Phone Number: 33118 +49913185; Email: axel.karow@uk-erlangen.de
• Study Contact Backup: Name: Alexander Dierl, MD; Phone Number: 33118 +49913185; Email: alexander.dierl@uk-erlangen.de

Study Locations

• Germany
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • Recruiting
      • Department of Pediatrics and Adolescent Medicine
      • Contact: Ferdinand Knieling, MD; Phone Number: +49 9131 8533118; Email: ferdinand.knieling@uk-erlangen.de
      • Contact: Axel Karow, MD; Phone Number: +49 9131 8533118; Email: axel.karow@uk-erlangen.de
      • Sub-Investigator: Alexander Dierl, MD
      • Sub-Investigator: Maximilian Hinsen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Study arm: "Early therapeutic effects"

Inclusion Criteria:

• Diagnosed acute lymphatic leukemia or Hodgkin's disease (HD)
• Completed induction therapy or radiotherapy

Exclusion Criteria:

• Pregnancy, Lactation
• Known pleural or pericardial effusion
• Critical condition (requiring respiratory support, ventilation, oxygen, shock, symptomatic heart failure)
• Marked thoracic deformities/malformations
• Previous lung surgery
• Injuries that do not allow physical stress diagnostics
• Rejection of MRI imaging
• General contraindications for MRI examinations (e.g. electrical implants such as cardiac pacemakers or perfusion pumps, etc.)

Study arm: "Late therapeutic effects"

Inclusion Criteria:

• Diagnosed acute lymphatic leukemia or Hodgkin's disease (HD)
• Completed intensive therapy or radiotherapy

Exclusion Criteria:

• Pregnancy, Lactation
• Known pleural or pericardial effusion
• Critical condition (requiring respiratory support, ventilation, oxygen, shock, symptomatic heart failure)
• Marked thoracic deformities/malformations
• Previous lung surgery
• Injuries that do not allow physical stress diagnostics
• Rejection of MRI imaging
• General contraindications for MRI examinations (e.g. electrical implants such as cardiac pacemakers or perfusion pumps, etc.)

Study arm: "Effects of hematopoietic stem cell transplantation"

Inclusion Criteria:

• Diagnosed acute lymphatic leukemia
• Completed hematopoietic stem cell transplantation

Exclusion Criteria:

• Pregnancy, Lactation
• Known pleural or pericardial effusion
• Critical condition (requiring respiratory support, ventilation, oxygen, shock, symptomatic heart failure)
• Marked thoracic deformities/malformations
• Previous lung surgery
• Injuries that do not allow physical stress diagnostics
• Rejection of MRI imaging
• General contraindications for MRI examinations (e.g. electrical implants such as cardiac pacemakers or perfusion pumps, etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early therapeutic effects; Diagnosed acute lymphatic leukemia or Hodgkin's disease (HD) and completed induction therapy or radiotherapy, from 5 years to <18 years	Diagnostic test: Low-field magnetic resonance imaging; Imaging of lung parenchyma and function by LF-MRI; Diagnostic test: Cardiopulmonary testing; Myocardial function (Strain-Analysis by echocardiography) and spiroergometry, capillary blood gases and lactate; Diagnostic test: Pulmonary testing; Lung function (VC%, FEV1%); Diagnostic test: Blood sample; Standard procedures/parameters routinely available in follow-up care after oncological treatment
Experimental: Late therapeutic effects; Diagnosed acute lymphatic leukemia or Hodgkin's disease (HD) and completed intensive therapy or radiotherapy, Patient in follow-up care, from 5 years to <18 years	Diagnostic test: Low-field magnetic resonance imaging; Imaging of lung parenchyma and function by LF-MRI; Diagnostic test: Cardiopulmonary testing; Myocardial function (Strain-Analysis by echocardiography) and spiroergometry, capillary blood gases and lactate; Diagnostic test: Pulmonary testing; Lung function (VC%, FEV1%); Diagnostic test: Blood sample; Standard procedures/parameters routinely available in follow-up care after oncological treatment
Experimental: Effects of hematopoietic stem cell transplantation; Diagnosed acute lymphatic leukemia, completed hematopoietic stem cell transplantation, from 5 years to <18 years	Diagnostic test: Low-field magnetic resonance imaging; Imaging of lung parenchyma and function by LF-MRI; Diagnostic test: Cardiopulmonary testing; Myocardial function (Strain-Analysis by echocardiography) and spiroergometry, capillary blood gases and lactate; Diagnostic test: Pulmonary testing; Lung function (VC%, FEV1%); Diagnostic test: Blood sample; Standard procedures/parameters routinely available in follow-up care after oncological treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morphologic lung assessment (LF-MRI)	Morphologic changes in lung parenchyma	Single time point (1 day)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional lung assessment (LF-MRI)	Change in functional lung parameters	Single time point (1 day)
Cardiopulmonary testing (VO2)	Oxygen uptake	Single time point (1 day)
Cardiopulmonary testing (VO2max)	Peak oxygen uptake	Single time point (1 day)
Cardiopulmonary testing (RER)	Respiratory exchange ratio	Single time point (1 day)
Cardiopulmonary testing (VT2)	Ventilatory anaerobic threshold	Single time point (1 day)
Cardiopulmonary testing (VCO2)	Carbon dioxide output	Single time point (1 day)
Cardiopulmonary testing (HR)	Heart rate	Single time point (1 day)
Cardiopulmonary testing (HRR)	Heart Rate Reserve	Single time point (1 day)
Cardiopulmonary testing (Breath rate at VAT)	Breath rate at VAT	Single time point (1 day)
Cardiopulmonary testing (BRR)	Breath rate reserve	Single time point (1 day)
Cardiopulmonary testing (VE)	Minute Ventilation	Single time point (1 day)
Cardiopulmonary testing (O2-Pulse)	O2-Pulse	Single time point (1 day)
Cardiopulmonary testing (HRV)	Heart rate variability	Single time point (1 day)
Cardiopulmonary testing (Borg-Scale)	Exercise capacity (Borg-Scale)	Single time point (1 day)
Cardiopulmonary testing (VO2)	Capillary blood gases and lactate	Single time point (1 day)
Cardiopulmonary testing (Strain-Analysis)	Strain-Analysis by echocardiography	Single time point (1 day)
Pulmonary test (Lung function)	Lung function (VC%, FEV1%)	Single time point (1 day)
Blood sample (Blood count)	Blood Count	Single time point (1 day)
Blood sample (Enterocytes)	Concentration of Enterocytes	Single time point (1 day)
Blood sample (Liver enzymes)	Liver enzymes	Single time point (1 day)
Blood sample (Retention parameters)	Concentration of kreatinin and urea	Single time point (1 day)
Weight	Weight of the participant in kilograms	Single time point (1 day)
Height	Height of the participant in meters	Single time point (1 day)

Collaborators and Investigators

• Sponsor: University of Erlangen-Nürnberg Medical School
• Investigators: Principal Investigator: Ferdinand Knieling, MD, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen; Principal Investigator: Axel Karow, MD, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen; Principal Investigator: Rafael Heiß, MD, Institute of Radiology, University Hospital Erlangen

Publications and helpful links

General Publications

• Erdmann F, Frederiksen LE, Bonaventure A, Mader L, Hasle H, Robison LL, Winther JF. Childhood cancer: Survival, treatment modalities, late effects and improvements over time. Cancer Epidemiol. 2021 Apr;71(Pt B):101733. doi: 10.1016/j.canep.2020.101733. Epub 2020 May 24.
• Silverman LB. Balancing cure and long-term risks in acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program. 2014 Dec 5;2014(1):190-7. doi: 10.1182/asheducation-2014.1.190. Epub 2014 Nov 18.
• Gebauer J, Baust K, Bardi E, Grabow D, Stein A, van der Pal HJ, Calaminus G, Langer T. Guidelines for Long-Term Follow-Up after Childhood Cancer: Practical Implications for the Daily Work. Oncol Res Treat. 2020;43(3):61-69. doi: 10.1159/000504200. Epub 2020 Jan 13.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2023
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: October 4, 2023
• First Submitted That Met QC Criteria: October 16, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): October 25, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Leukemia; Hodgkin Disease; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: 23-47-B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication.

IPD Sharing Access Criteria

The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request as follows:

Individual participant data will not be available Study Protocol and Statistical Analysis Plan will be available The data will be available beginning 9 months and ending 36 months following article publication.

The data will be available to researchers who provide a methodologically sound proposal.

The data will be available for individual participant data meta-analysis, only. Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing data may be found at https://www.uk-erlangen.de.

Restrictions may apply due to patient privacy and the General Data Protection Regulation.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No