Clinical trial NCT06093334: Imaging of Chemotherapy-induced Morphological and Functional Lung Changes in Childhood ALL and HD
Official title: iMagINg of Chemotherapy-Induced Morphological and Functional Lung Changes in Childhood Acute Lymphoblastic Leukemia and Hodgkin's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Lymphoblastic Leukemia
Hodgkin Disease
Allogeneic Stem Cell Transplantation
Lead sponsor: University of Erlangen-Nürnberg Medical School
Sponsor class: OTHER
First posted: 2023-10-23
Enrollment: 27
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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.

Eligibility criteria: 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.)

Primary outcomes:
measure: Morphologic lung assessment (LF-MRI)
timeFrame: Single time point (1 day)
Secondary outcomes:
measure: Functional lung assessment (LF-MRI)
timeFrame: Single time point (1 day)
measure: Cardiopulmonary testing (VO2)
timeFrame: Single time point (1 day)
measure: Cardiopulmonary testing (VO2max)
timeFrame: Single time point (1 day)
measure: Cardiopulmonary testing (RER)
timeFrame: Single time point (1 day)
measure: Cardiopulmonary testing (VT2)
timeFrame: Single time point (1 day)
measure: Cardiopulmonary testing (VCO2)
timeFrame: Single time point (1 day)
measure: Cardiopulmonary testing (HR)
timeFrame: Single time point (1 day)
measure: Cardiopulmonary testing (HRR)
timeFrame: Single time point (1 day)
measure: Cardiopulmonary testing (Breath rate at VAT)
timeFrame: Single time point (1 day)
measure: Cardiopulmonary testing (BRR)
timeFrame: Single time point (1 day)
measure: Cardiopulmonary testing (VE)
timeFrame: Single time point (1 day)
measure: Cardiopulmonary testing (O2-Pulse)
timeFrame: Single time point (1 day)
measure: Cardiopulmonary testing (HRV)
timeFrame: Single time point (1 day)
measure: Cardiopulmonary testing (Borg-Scale)
timeFrame: Single time point (1 day)
measure: Cardiopulmonary testing (VO2)
timeFrame: Single time point (1 day)
measure: Cardiopulmonary testing (Strain-Analysis)
timeFrame: Single time point (1 day)
measure: Pulmonary test (Lung function)
timeFrame: Single time point (1 day)
measure: Blood sample (Blood count)
timeFrame: Single time point (1 day)
measure: Blood sample (Enterocytes)
timeFrame: Single time point (1 day)
measure: Blood sample (Liver enzymes)
timeFrame: Single time point (1 day)
measure: Blood sample (Retention parameters)
timeFrame: Single time point (1 day)
measure: Weight
timeFrame: Single time point (1 day)
measure: Height
timeFrame: Single time point (1 day)
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: Department of Pediatrics and Adolescent Medicine
state: Bavaria
Study officials:
affiliation: Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen
name: Axel Karow, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen
name: Ferdinand Knieling, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Radiology, University Hospital Erlangen
name: Rafael Heiß, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.