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

Sponsor
Stichting Hemato-Oncologie voor Volwassenen Nederland
Study ID
NCT06220032
Phase
PHASE3
Status
Recruiting
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Conditions

  • DLBCL - Diffuse Large B Cell Lymphoma

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Dexrazoxane — DRUG
    Day 1 Cycle 1-6: Dexrazoxane 500 mg/m2 (iv) will be given 30 minutes before doxorubicin infusion and should be infused during 15 minutes.
  • Rituximab — DRUG
    Day 1 Cycle 1-6: 375 mg/m2 (iv)
  • Cyclophosphamide — DRUG
    Day 1 Cycle 1-6: 750 mg/m2 (iv)
  • Doxorubicin — DRUG
    Day 1 Cycle 1-6: 50 mg/m2 (iv)
  • Vincristine — DRUG
    Day 1 Cycle 1-6: 1.4 mg/m2 (max 2 mg) (iv)
  • Prednisolone — DRUG
    Day 1-5 Cycle 1-6: 100 mg (oral)
  • Lenalidomide — DRUG
    Day 1-14 Cycle 1-6: 15 mg day (oral) Only in case of a double hit lymphoma.
  • Pegfilgrastim — DRUG
    6 mg (1 dose per cycle) in case of neutropenia. Pegfilgastim is mandatory in patients that receive R2-CHOP21.

Study Details

Patients treated for DLBCL are at high risk of developing AICD. This adverse event is characterized by irreversible damage to the heart muscle with a loss of cardiomyocytes and subsequent decline in cardiac pumping capacity. Thereby patients treated for this malignancy are at double the risk of developing symptomatic heart failure / cardiomyopathy when compared to the general population. This corresponds to a cumulative incidence of 5-10% within 5-years after receiving R-CHOP. In the elderly, an incidence of 26% has been reported after 8-years of follow-up. Among patients who die in complete remission, heart failure has been described to be one of the most important causes of death. ANTICIPATE aims to evaluate if dexrazoxane can prevent AICD in DLBCL patients and identify those at highest risk of AICD. Of all patients treated with anthracyclines in a first-line setting, DLBCL patients were chosen for this trial for two primary reasons. Firstly, these patients have a favourable oncological prognosis with a 5-year relative survival in the Netherlands of 64-78% in those aged 18-74 years increasing the importance of preventing long-term toxicity. Secondly, the cumulative anthracycline dose used for the treatment of DLBCL is higher than the dose used in breast cancer. The cumulative anthracycline dose is the most important risk factor for AICD known.

Key Dates

Start date
Aug 15, 2024
Status verified
Oct 2025
Primary completion
Dec 15, 2028
Completion
Dec 15, 2028

Study Design

Enrollment
324 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Arm A
    Standard R-CHOP 21 treatment regimen: 6 cycles R-CHOP 21 (rituximab\*, cyclophosphamide, doxorubicin, vincristine, prednisolone) \*The use of a biosimilar is allowed.
  • Experimental: Arm B -
    Addition of the cardioprotectant dexrazoxane to the R-CHOP 21 regimen: R-CHOP21 (rituximab\*, cyclophosphamide, doxorubicin, vincristine, prednisolone plus dexrazoxane). \*The use of a biosimilar is allowed.

Primary Outcome Measure

The incidence of AICD. [ Time Frame: 12 months after LPI ]

Central Contacts

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