A Randomized, placebo-controlled, double-blinded Phase 2 Trial of Dapagliflozin for Preventing Treatment-associated Cardiotoxicity in Lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aalborg University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Mar 2026 → ongoing

Decision date (initial)

2025-09-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novo Nordisk Foundation · The Danish Cancer Society

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

The primary objective of this study is to investigate the cardioprotective effects of an SGLT2 inhibitor administered to patients with lymphoma during first line treatment with (R-)CHO(E)P.

Conditions and MedDRA coding

Diffuse large B-cell lymphoma NOS, follicular lymphoma Grade 3b, anaplastic large T-cell lymphoma (ALK positive), follicular lymphoma grade 1-3a, and T-cell lymphomas.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Diffuse large B-cell lymphoma NOS, follicular lymphoma Grade 3b, anaplastic large T-cell lymphoma (ALK positive), follicular lymphoma grade 1-3a, and T-cell lymphomas not planned for stem cell transplantation in first line
2. Planned for 6 cycles of full standard dose (R-)CHOP or (R-)CHOEP
3. Baseline ejection fraction ≥50% (GLS ≥ - 16)
4. Age ≥18 and ≤ 80 years
5. Written informed consent
6. Capable of reading and understanding the Danish language
7. Safe contraception for both men and women when relevant as described in detail in section 13
8. Willingness to comply with protocol specified procedures; the investigator believes that the subject understands what the study entails, is capable of following instructions, can attend when needed, and is expected to complete the study

Exclusion criteria 13

1. Ongoing treatment with SGLT2 inhibitors or prior intolerability
2. Diabetes (type 1 or type 2)
3. Any significant heart diseases precluding full-dose anthracycline therapy based on investigator assessment
4. Atrial fibrillation or atrial flutter
5. Ongoing statin therapy
6. Ongoing treatment with angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ACEi/ARB)
7. Kidney disease with eGFR <60 ml/min or creatinine > 2x upper normal value
8. Severe liver disease hindering full standard dose (R-)CHOP or (R-)CHOEP
9. Daily use of loop-diuretic therapy
10. Lithium therapy
11. Planned radiotherapy against mediastinal bulk
12. Alcohol abuse (defined as >4 standard drinks/day and >10 standard drinks/week) or any drug abuse
13. Allergy to study drug ingredients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the change in global longitudinal strain between baseline and first month after end of treatment, where we define a ≥10% reduction as significant and indicative of cardiotoxicity in agreement with previous published studies.

Secondary endpoints 9

1. Diastolic parameter changes including the mitral valve filling pattern assessed by Doppler velocity measurements, the E/A ratio representing the early wave velocity (E) to the late velocity after atrial contraction (A), the deceleration time of the E wave, the early and late velocities of the mitral annulus measured by tissue Doppler (e′ and a′), isovolumetric relaxation time (IVRT), the left atrial volume, and the derived E/ e′.
2. Change in right ventricle related parameters including TAPSE and TRmax
3. LVEF change assessed using WMI and Simpson biplane in addition to change in cardiac output assessed using VTI.
4. Change in serum values of troponin T or I and N-Terminal pro-B-type natriuretic peptide (NT-proBNP) or proBNP.
5. ECG findings and changes in relation to echocardiographic measurements and rate of heart failure
6. Rate of heart failure in the placebo and SGLT2 inhibitor arm
7. Coronary artery calcium score in pre-planned, interim and end of treatment computer tomography (CT) scans in relation to ischemic heart disease and heart failure
8. Cardiopulmonary symptoms during follow-up using New York Heart Association (NYHA).
9. Tolerability of SGLT2 inhibitors administered in combination with R-CHOP, assessed using descriptive summaries of CTCAE reportings and dose reductions/interruptions/discontinuations

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aalborg University Hospital

Sponsor organisation

Aalborg University Hospital

Address

Hobrovej 18-22

City

Aalborg

Postcode

9000

Country

Denmark

Scientific contact point

Organisation

Aalborg University Hospital

Contact name

Kristian Hay Kragholm

Public contact point

Organisation

Aalborg University Hospital

Contact name

Kristian Hay Kragholm

Third parties 2

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications