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

Prior treatment

• Ongoing treatment with SGLT2 inhibitors or prior intolerability
• Ongoing treatment with angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ACEi/ARB; patients can be included if ACEi/ARB are discontinued at inclusion)
• Planned consolidation therapy with high-dose therapy and autologous stem cell transplantation
• Lithium therapy
• Planned radiotherapy against mediastinal bulk
• Alcohol abuse (defined as >4 standard drinks/day and >10 standard drinks/week) or any drug abuse
• Ongoing statin therapy (patients can be included if it is considered safe to discontinue statins during the study)

Other illness

• Severe liver disease hindering full standard dose (R-)CHOP or (R-)CHOEP
• Allergy to study drug ingredients
• Diabetes (type 1 or type 2)
• Any significant heart diseases precluding full-dose anthracycline therapy based on investigator assessment

Lab values

• Kidney disease with eGFR <45 ml/min or creatinine > 2x upper normal value

Other

• Ongoing use of mineralocorticoid receptor antagonist (MRA); patients can be included if it is considered safe to discontinue MRA during the study.
• Use of loop diuretics at a total daily dose exceeding 80 mg furosemide (or equivalent); patients can be included if it is safe to reduce the daily dose to a maximum of 80 mg furosemide (or equivalent) during the study treatment
• Atrial fibrillation or atrial flutter

• Diffuse large B-cell lymphoma (all subtypes), any type of large B-cell lymphomas, mediastinal B-cell lymphomas (including PMBL and grey zone lymphomas), follicular lymphoma Grade 3b, anaplastic large T-cell lymphoma (ALK positive), follicular lymphoma grade 1-3a, T-cell lymphomas not planned for stem cell transplantation in first line, or transformed lymphoma from any type of indolent lymphoma/CLL
• Planned for 6 cycles of full standard dose (R-)CHOP or (R-)CHOEP
• Baseline ejection fraction ≥50% and GLS ≥ - 16
• Age ≥18 and ≤ 80 years
• Written informed consent
• Capable of reading and understanding the Danish language
• Safe contraception for both men and women when relevant as described in detail in section 13
• 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