Clinical trial NCT06449625: Semaglutide in Auto-HSCT
Official title: Semaglutide Treatment for PRevention Of Toxicity in High-dose Chemotherapy With Autologous Haematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Intestinal Mucositis
Inflammation
Chemotherapeutic Toxicity
Keywords: Gut epithelial barrier
Chemotherapy-induced toxicity
Growth factor
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
name: Independent Research Fund Denmark
First posted: 2024-06-10
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized 1:1
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: gastrointestinal mucositis severity
timeFrame: from day of stem cell infusion (day 0) to week +3
Secondary outcomes:
measure: CRP increment
timeFrame: from day of stem cell infusion (day 0) to week +3
measure: Quality of life general
timeFrame: change from baseline (start of high-dose chemotherapy) to study week 9 and 18
measure: Quality of life - high-dose chemotherapy treatment specific
timeFrame: change from baseline (start of high-dose chemotherapy) to study week 9 and 18
measure: Safety profile evaluated by number of SARs
timeFrame: Start of study drug treatment (week 1) until study week 10
Other outcomes:
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