Chemotherapeutic Toxicity, Inflammation, Intestinal Mucositis
Conditions
Keywords
Gut epithelial barrier, Chemotherapy-induced toxicity, Growth factor
Brief summary
The primary objective of this clinical trial is to ievaluate the effect of semaglutide (GLP-1 receptor agonist) in reducing intensity of gastrointestinal (GI) mucositis in patients undergoing high-dosage chemotherapy followed by autologous (auto) haematopoietic stem cell transplantation (HSCT). The secondary objective is to evaluate the effect and safety of semaglutide in reducing gut barrier injury and systemic inflammation in patients undergoing auto-HSCT. Study design: The study is designed as a randomized, double-blind, placebo-controlled, phase 2, two-centre investigator-initiated clinical study. Patients referred for treatment with high-dose chemotherapy and auto-HSCT will be randomized in a 1:1 manner to receive either semaglutide or placebo. The study includes a run-in period 3 to 4-week low-dose period with semaglutide subcutaneously (s.c.) 0.25 mg once-weekly (QW) prior to high-dose chemotherapy treatment followed by a period of 4 to 5 weeks with semaglutide 0.5 mg QW. Total duration of treatment with investigational drug will be 8 weeks. Total study duration for the individual patients will be 20-22 weeks, including a 2-4-week screening period and 10 weeks of follow-up. Study population: A planned total number of 40 patients will be randomized.
Interventions
Semaglutide active drug
DRUGPlacebo
semaglutide placebo
Sponsors
Novo Nordisk A/S
Independent Research Fund Denmark
Klaus Gottlob Müller
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
randomized 1:1
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Referral for auto-HSCT for relapsed diffuse large B-cell lymphoma or follicular lymphoma * Age ≥ 18 years * BMI ≥ 18.5 * ECOG performance status\* ≤ 2 * Literate in Danish and/or English
Exclusion criteria
* Diabetes * Inflammatory bowel disease * Previous or current gastrointestinal malignancy * Personal or family history of medullary thyroid carcinoma or MEN syndrome * Genetic disorders with defective tissue repair (e.g., Fanconi anaemia) * History of pancreatitis (acute or chronic) * Renal impairment measured as eGFR value of \< 30 ml/min/1.73 m2 * Impaired liver function, defined as alanine aminotransferase ≥ 2.5 times upper normal limit at screening * Known or suspected hypersensitivity to semaglutide or other GLP-1RA * Pregnant or nursing females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| gastrointestinal mucositis severity | from day of stem cell infusion (day 0) to week +3 | mean severity grade (0-II) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CRP increment | from day of stem cell infusion (day 0) to week +3 | AUC |
| Quality of life general | change from baseline (start of high-dose chemotherapy) to study week 9 and 18 | evaluated by EORTC QLQ-C30 questionnaire. The QLQ-C30 summary score is calculated as the mean of the combined 13 QLQ-C30 scale and item scores (excluding global QoL and financial impact). Final scoring range: 0-100 with a higher score indicating a better quality of life |
| Quality of life - high-dose chemotherapy treatment specific | change from baseline (start of high-dose chemotherapy) to study week 9 and 18 | evaluated by EORTC QLQ-HDC29 questionnaire. The QLQ HDC29 module includes 29 items, consisting of 6 multi-item scales and 8 singleitems. Final scoring range: 0-100 with a higher score indicating a better quality of life |
| Safety profile evaluated by number of SARs | Start of study drug treatment (week 1) until study week 10 | SAR will be estimated according to ICH-GCP guidelines |
Contacts
Primary ContactMaria Ebbesen Sørum, MD, PhD
Backup ContactKlaus Müller, DMSc
Outcome results
None listed