Prevention of Anthracycline-Induced Cardiac Dysfunction With Dexrazoxane in Patients With Diffuse Large-B Cell Lymphoma

Inclusion Criteria:

1. Untreated patients with a confirmed histologic diagnosis of CD20+ DLBCL according toWHO classification 2022:

• DLBCL, not otherwise specified (NOS)

• High-grade B-cell lymphoma NOS

• High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 translocation whenDA-EPOCH-R is not an option. R2- CHOP is allowed.

• Follicular lymphoma

• T-cell/histiocyte-rich B cell lymphoma (THRBCL) Note: Transformed, previously untreated lymphoma is allowed. Note: 5-day treatment of dexamethasone 15 mg/day or prednisone 100 mg/day or localradiotherapy in order to control life-threatening/invalidating tumor relatedsymptoms is allowed. Note: It is allowed to start with a first cycle of R-CHOP21 pending the FISHresults.

2. Planned treatment with 6 R-CHOP21. The following regimens are also allowed:

• Treatment with reversed R-CHOP21

• Treatment with R2-CHOP21 (6 R-CHOP21 + lenalidomide 15 mg day 1-14) in case ofdouble hit lymphoma

• Two additional administrations of rituximab after 6 cycles of R-CHOP21

• High dosis MTX and/or MTX-it for CNS prophylaxis

3. Ann Abor stages II-IV and stage I if the treatment plan is 6 R-CHOP21 in case ofbulky disease (defined as a ≥10 cm mass);

4. Age ≥ 18 years;

5. WHO performance status ≤ 2, WHO 3 performance status is allowed when considereddirectly related to the DLBCL;

6. Negative pregnancy test at study entry for women of childbearing potential;

7. Female patient is either post-menopausal for at least 1 year before the screeningvisit or surgically sterile or if of childbearing potential, agrees to practice twoeffective methods of contraception, at the same time, from the time of signing theinformed consent through at least 12 months after the last dose of protocoltreatment, or agrees to completely abstain from heterosexual intercourse;

8. Male patient, even if surgically sterilized, (i.e., status post vasectomy) agrees topractice effective barrier contraception during the entire study period and through 12 months after the last dose of protocol treatment, or agrees to completely abstainfrom heterosexual intercourse;

9. Patient is able to adhere to the study visit schedule and other protocolrequirements;

10. Written informed consent.

Exclusion Criteria:

1. Any of the following B-cell lymphomas according to WHO classification 2022: o Central Nervous System involvement by DLBCL; Note: high CNS-IPI is allowed

• Testicular DLBCL;

• Primary mediastinal B-cell lymphoma;

• Epstein-Barr virus (EBV) post-transplant lymphoproliferative disorder;

2. Any prior malignancy or present malignancy other than DLBCL that required orrequires systemic therapy. Prior surgery or local radiotherapy is allowed in casethe heart has not been exposed.

3. Patients requiring treatment with mini-R-CHOP

4. Pre-existing cardiac disease including:

• LVEF <50% measured with echocardiography (2D or 3D)

• Symptomatic heart failure (NYHA ≥II) or hospitalization for heart failure inthe last year;

• Refractory anginal symptoms

• Cardiac arrhythmias not controlled with optimal medical treatment, in case ofatrial fibrillation the ventricular response needs to be <110/min;

• Significant valvular dysfunction on echocardiography;

• Non-ischemic cardiomyopathy

5. Non-diagnostic/poor transthoracic echocardiography imaging quality at baseline;

6. Severe pulmonary dysfunction defined as breathlessness at rest (COPD GOLD III orIV), unless clearly related to DLBCL;

7. Severe neurological or psychiatric disease;

8. Inadequate hematological function (absolute Neutrophil Count (ANC) <1.0x109/L orplatelets <75x109/L), unless clearly related to DLBCL;

9. Significant hepatic dysfunction (serum bilirubin or transaminases ≥ 3 times theupper limit of normal) unless related to lymphoma infiltration of the liver;

10. Active hepatitis B or C infection (serology testing is required at screening).Patients positive for hepatitis B surface antigen (HBsAg) regardless of antibodystatus or HBsAg negative but anti-HBc positive are only eligible if HBV-PCR isnegative and patients are protected with lamuvidine or entecavir. Patients withpositive hepatitis C serology are only eligible if HCV-(RNA) is confirmed negative;

11. Significant renal dysfunction (creatinine clearance < 30 ml/min after rehydration)or requiring dialysis;

12. Active uncontrolled fungal, bacterial and/or viral infection;

13. Patient known to be HIV-positive;

14. Breast-feeding female patients;

15. Any psychological, familial, sociological and geographical condition potentiallyhampering compliance with the study protocol and follow-up schedule;

16. Participation in another clinical trial with anti-cancer therapy or a cardiovasculardrug.