A Randomized, Double-Blind, Phase 2 Trial Evaluating the Efficacy, Safety and Tolerability of Primary Cardioprotection with Dapagliflozin in Patients with Newly Diagnosed Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation

Prior treatment

• Major surgical procedure within 30 days prior to randomization
• Any significant concomitant diseases or clinical conditions constituting a contraindication to therapy or participation in the HEART-DAPA-MM clinical trial
• Patients with contraindications to the use of flozins (SGLT2 inhibitors) according to the current Summary of Product Characteristics (SmPC).
• Patients taking flozins (SGLT2 inhibitors) in the last 3 months

Other illness

• A history of active malignancy or ongoing anti-cancer treatment other than MM that could affect interpretation of study results
• History or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
• Hypersensitivity to any study drug or any of its excipients
• Any anti-cancer treatment for multiple myeloma before study entry
• Known or suspected systemic light-chain amyloidosis with organ involvement (including, but not limited to, cardiac, renal, hepatic, gastrointestinal, or autonomic nervous system involvement), judged by the Investigator to confer unacceptable risk for high-dose chemotherapy and/or auto-HSCT
• Type 1 diabetes mellitus
• Patients with active, severe bacterial, viral, or fungal infection at the time of eligibility assessment are not eligible for chemotherapy and/or autologous hematopoietic stem cell transplantation (auto- HSCT)
• Active mental illness that prevents cooperation of the patient

Lab values

• Cardiologic exclusion criteria specified in protocol: a. diagnosis of HF before MM diagnosis b. left ventricular ejection fraction (LVEF) <50% at baseline c. myocardial infarction or stroke within 90 days before enrollment; d. systolic blood pressure <95 mmHg on multiple consecutive measurements at screening and/or before randomization e. uncontrolled hypertension with blood pressure values >180/110 mmHg during visit S1 and V1 despite treatment with multiple antihypertensive medications according to current ESC guidelines. f. permanent / chronic atrial fibrillation/atrial flutter (Presence of cardiac pacemaker is not an exclusion criterion provided sinus rhythm is maintained).

Other

• Subjects with known central nervous system involvement with myeloma
• Pregnancy, breast feeding
• Plasma cell leukemia

• Able to provide informed consent to participate in the study (including consent for translational research samples, if applicable)
• Obtaining informed consent including translational research samples, if applicable
• Males and females ≥18 years of age at the time of signing informed consent form (ICF)
• Documented diagnosis of MM according to IMWG diagnostic criteria
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 - 2
• Patients who are eligible for high dose chemotherapy and auto-HSCT procedure within NFZ drug program B.54 and per local investigational site practice
• Adequate systems/organs function as determined based on the results of laboratory blood tests, enabling safe initiation of anticancer therapy in the opinion of the Investigator, including: liver function: bilirubin <1.5 ULN and ALT <3 ULN (Not applicable to patients with Gilbert syndrome and liver plasmacytoma) renal function: creatinine clearance (as eGFR) >25 ml ml/min/1.73m2
• Patients with reproductive potential must consent to use highly effective methods of contraception during the study and for 28 days after the last dose of chemotherapy or study treatment, whatever comes later