DEXRAZOXANE for Diffuse large B-cell lymphoma (DLBCL)

Inclusion criteria

• {"criterion_text":"- Untreated patients with a confirmed histologic diagnosis of CD20+ DLBCL according to the WHO 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 when DA-EPOCH-R is not an option (R2-CHOP is allowed); Follicular lymphoma; T-cell/histiocyte-rich B cell lymphoma (THRBCL)."}
• {"criterion_text":"- Written informed consent."}
• {"criterion_text":"- 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 of double hit lymphoma; Two additional administrations of rituximab after 6 cycles of R-CHOP21; High dosis MTX and/or MTX-it for CNS prophylaxis."}
• {"criterion_text":"- Ann Abor stages II-IV and stage I if the treatment plan is 6 R-CHOP21 in case of bulky disease (defined as a ≥10 cm mass)."}
• {"criterion_text":"- Age ≥ 18 years."}
• {"criterion_text":"- WHO performance status ≤ 2, WHO 3 performance status is allowed when considered directly related to the DLBCL."}
• {"criterion_text":"- Negative pregnancy test at study entry for women of childbearing potential."}
• {"criterion_text":"- Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, agrees to practice two effective methods of contraception, at the same time, from the time of signing the informed consent through at least 12 months after the last dose of protocol treatment, or agrees to completely abstain from heterosexual intercourse."}
• {"criterion_text":"- Male patient, even if surgically sterilized, (i.e., status post vasectomy) agrees to practice effective barrier contraception during the entire study period and through 12 months after the last dose of protocol treatment, or agrees to completely abstain from heterosexual intercourse."}
• {"criterion_text":"- Patient is able to adhere to the study visit schedule and other protocol requirements."}

Exclusion criteria

• {"criterion_text":"- Any of the following B-cell lymphomas according to WHO classification 2022: Central Nervous System involvement by DLBCL (high CNS-IPI is allowed); Testicular DLBCL; Primary mediastinal B-cell lymphoma; Epstein-Barr virus (EBV) post-transplant lymphoproliferative disorder."}
• {"criterion_text":"- Active hepatitis B or C infection (serology testing is required at screening). Patients positive for hepatitis B surface antigen (HBsAg) regardless of antibody status or HBsAg negative but anti-HBc positive are only eligible if HBV-PCR is negative and patients are protected with lamuvidine or entecavir. Patients with positive hepatitis C serology are only eligible if HCV-(RNA) is confirmed negative."}
• {"criterion_text":"- Significant renal dysfunction (creatinine clearance < 30 ml/min after rehydration) or requiring dialysis."}
• {"criterion_text":"- Active uncontrolled fungal, bacterial and/or viral infection."}
• {"criterion_text":"- Patient known to be HIV-positive."}
• {"criterion_text":"- Breast-feeding female patients."}
• {"criterion_text":"- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule."}
• {"criterion_text":"- Participation in another clinical trial with anti-cancer therapy or a cardiovascular drug."}
• {"criterion_text":"- Any prior malignancy or present malignancy other than DLBCL that required or requires systemic therapy. Prior surgery or local radiotherapy is allowed in case the heart has not been exposed."}
• {"criterion_text":"- Patients requiring treatment with mini-R-CHOP."}
• {"criterion_text":"- Pre-existing cardiac disease including: LVEF <50% measured with echocardiography (2D or 3D); Symptomatic heart failure (NYHA ≥II) or hospitalization for heart failure in the last year; Refractory anginal symptoms; Cardiac arrhythmias not controlled with optimal medical treatment, in case of atrial fibrillation the ventricular response needs to be <110/min; Significant valvular dysfunction on echocardiography; Non-ischemic cardiomyopathy."}
• {"criterion_text":"- Non-diagnostic/poor transthoracic echocardiography imaging quality at baseline."}
• {"criterion_text":"- Severe pulmonary dysfunction defined as breathlessness at rest (COPD GOLD III or IV), unless clearly related to DLBCL."}
• {"criterion_text":"- Severe neurological or psychiatric disease."}
• {"criterion_text":"- Inadequate hematological function (absolute Neutrophil Count (ANC) <1.0x109 /L or platelets <75x109 /L), unless clearly related to DLBCL."}
• {"criterion_text":"- Significant hepatic dysfunction (serum bilirubin or transaminases ≥ 3 times the upper limit of normal) unless related to lymphoma infiltration of the liver."}

Primary endpoints

• {"endpoint_text":"- The incidence of AICD (measured with 2D) within 12-months after registration.","definition_or_measurement_approach":"Measured with 2D echocardiography within 12 months after registration (incidence of anthracycline-induced cardiac dysfunction)."}
• {"endpoint_text":"- Complete metabolic remission (CMR) on 18F-FDG PET-CT at end of treatment 6-8 weeks after completion of 6x R-CHOP21.","definition_or_measurement_approach":"CMR assessed by 18F-FDG PET-CT at end of treatment, 6-8 weeks after completion of 6 cycles of R-CHOP21."}

Secondary endpoints

• {"endpoint_text":"- Overall survival (OS) at 12-months.","definition_or_measurement_approach":"Overall survival measured at 12 months after registration."}
• {"endpoint_text":"- Progression-free survival (PFS) at 12-months.","definition_or_measurement_approach":"Progression-free survival measured at 12 months after registration."}
• {"endpoint_text":"- LVEF (2D and 3D) and global longitudinal strain (GLS) at end of treatment and 12-months after start of treatment.","definition_or_measurement_approach":"LVEF measured by 2D and 3D echocardiography and GLS measurements at end of treatment and at 12 months after start of treatment."}
• {"endpoint_text":"- NYHA functional class.","definition_or_measurement_approach":"NYHA functional class assessment as recorded in follow-up visits."}
• {"endpoint_text":"- Release of cardiac biomarkers.","definition_or_measurement_approach":"Measurement of cardiac biomarkers (troponin, NTpro-BNP) comparing treatment arms."}
• {"endpoint_text":"- Quality of Life score.","definition_or_measurement_approach":"Quality of life scores assessed using specified QoL instruments (not further specified in the JSON)."}
• {"endpoint_text":"- Safety and toxicity as defined by type, frequency and severity of adverse events as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.","definition_or_measurement_approach":"Adverse events recorded and graded according to NCI CTCAE v5.0."}
• {"endpoint_text":"- Incidence of secondary malignancies.","definition_or_measurement_approach":"Incidence of secondary malignancies assessed during follow-up."}
• {"endpoint_text":"- Major Adverse Cardiovascular Events (MACE) at 1-, 2-, 5- and 10-years.","definition_or_measurement_approach":"Incidence of MACE assessed at 1, 2, 5 and 10 years after treatment."}

Netherlands

Earliest CTIS Part Ii Submission Date

12-04-2024

Latest Decision Or Authorization Date

21-04-2026

Processing Time Days

739

Number Of Sites

25

Number Of Participants

324

Primary sponsor

Full Name

Stichting Hemato-Oncologie voor Volwassenen Nederland (Hovon)

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"Netherlands","full_name":"Universitair Medisch Centrum Utrecht","duties_or_roles":"ECHO core laboratory","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Netherlands","full_name":"Universitair Medisch Centrum Utrecht","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Netherlands","full_name":"Amsterdam UMC","duties_or_roles":"ECHO core laboratory","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Netherlands","full_name":"Universitair Medisch Centrum Utrecht","duties_or_roles":"Biobanking","organisation_type":"Hospital/Clinic/Other health care facility"}