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

• Sponsor: University of Erlangen-Nürnberg Medical School (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT06093334
• Collaborator: (none)
• Enrollment: 50
• Location: 1
• Arms: 3
• Anticipated Duration (Months): 13.5
• Patients Per Site Per Month: 3.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia; Hodgkin Disease; Allogeneic Stem Cell Transplantation	Diagnostic Test: Low-field magnetic resonance imaging; Diagnostic Test: Cardiopulmonary testing; Diagnostic Test: Pulmonary testing; Diagnostic Test: Blood sample	N/A

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 50 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: iMagINg of Chemotherapy-Induced Morphological and Functional Lung Changes in Childhood Acute Lymphoblastic Leukemia and Hodgkin's Disease
• Actual Study Start Date: Oct 17, 2023
• Anticipated Primary Completion Date: Oct 1, 2024
• Anticipated Study Completion Date: Dec 1, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Morphologic lung assessment (LF-MRI) [Single time point (1 day)]

   Morphologic changes in lung parenchyma

Secondary Outcome Measures

1. Functional lung assessment (LF-MRI) [Single time point (1 day)]

   Change in functional lung parameters

2. Cardiopulmonary testing (VO2) [Single time point (1 day)]

   Oxygen uptake

3. Cardiopulmonary testing (VO2max) [Single time point (1 day)]

   Peak oxygen uptake

4. Cardiopulmonary testing (RER) [Single time point (1 day)]

   Respiratory exchange ratio

5. Cardiopulmonary testing (VT2) [Single time point (1 day)]

   Ventilatory anaerobic threshold

6. Cardiopulmonary testing (VCO2) [Single time point (1 day)]

   Carbon dioxide output

7. Cardiopulmonary testing (HR) [Single time point (1 day)]

   Heart rate

8. Cardiopulmonary testing (HRR) [Single time point (1 day)]

   Heart Rate Reserve

9. Cardiopulmonary testing (Breath rate at VAT) [Single time point (1 day)]

   Breath rate at VAT

10. Cardiopulmonary testing (BRR) [Single time point (1 day)]

    Breath rate reserve

11. Cardiopulmonary testing (VE) [Single time point (1 day)]

    Minute Ventilation

12. Cardiopulmonary testing (O2-Pulse) [Single time point (1 day)]

    O2-Pulse

13. Cardiopulmonary testing (HRV) [Single time point (1 day)]

    Heart rate variability

14. Cardiopulmonary testing (Borg-Scale) [Single time point (1 day)]

    Exercise capacity (Borg-Scale)

15. Cardiopulmonary testing (VO2) [Single time point (1 day)]

    Capillary blood gases and lactate

16. Cardiopulmonary testing (Strain-Analysis) [Single time point (1 day)]

    Strain-Analysis by echocardiography

17. Pulmonary test (Lung function) [Single time point (1 day)]

    Lung function (VC%, FEV1%)

18. Blood sample (Blood count) [Single time point (1 day)]

    Blood Count

19. Blood sample (Enterocytes) [Single time point (1 day)]

    Concentration of Enterocytes

20. Blood sample (Liver enzymes) [Single time point (1 day)]

    Liver enzymes

21. Blood sample (Retention parameters) [Single time point (1 day)]

    Concentration of kreatinin and urea

22. Weight [Single time point (1 day)]

    Weight of the participant in kilograms

23. Height [Single time point (1 day)]

    Height of the participant in meters

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Pediatrics and Adolescent Medicine	Erlangen	Bavaria	Germany	91054

Sponsors and Collaborators

• University of Erlangen-Nürnberg Medical School

Investigators

• Principal Investigator: Axel Karow, MD, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen
• Principal Investigator: Ferdinand Knieling, MD, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen
• Principal Investigator: Rafael Heiß, MD, Institute of Radiology, University Hospital Erlangen

Study Documents (Full-Text)

• Study Protocol - Apr 27, 2023
• Statistical Analysis Plan - Sep 20, 2023

More Information

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.
• 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.
• 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.

• Responsible Party: University of Erlangen-Nürnberg Medical School
• ClinicalTrials.gov Identifier: NCT06093334
• Other Study ID Numbers: 23-47-B
• First Posted: Oct 23, 2023
• Last Update Posted: Oct 25, 2023
• Last Verified: Oct 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Hodgkin Disease

Study Results

No Results Posted as of Oct 25, 2023