Study Comparing ABVD vs BEACOPP in Advanced Hodgkin's Lymphoma
- Conditions
- Hodgkin Lymphoma
- Interventions
- Registration Number
- NCT01251107
- Lead Sponsor
- Fondazione Michelangelo
- Brief Summary
The choice of a preferred first-line treatment requires balancing the desire for optimal disease control with the occurrence of early and late treatment-related effects. To fully assess this balance, the treatment decision process should ideally take into account the outcome following a consistent second-line therapy, in particular when tolerated, widely applicable and highly effective salvage regimens exist, like in Hodgkin lymphoma failing initial chemotherapy.
- Detailed Description
During the last two decades ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) has been considered as the standard of care for advanced HL, however 20-30% of the patients fail to achieve a durable complete remission and need a salvage treatment. After a state-of-the art-salvage program including high-dose chemotherapy and autologous hematopoietic stem cell support (ASCT) at least half of these patients achieve a durable disease control. Recently the German Hodgkin Study Group (GHSG) has developed a new regimen, BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone), administered with or without dose escalation. In an interim analysis after 23 months follow-up, BEACOPP demonstrated a higher activity compared to COPP/ABVD with a superior freedom from treatment failure (84% versus 75%, P=.034). Despite the improved efficacy a substantial proportion of patients receiving escalated BEACOPP experienced severe acute hematologic toxicity (grade 3-4 leucopoenia, thrombocytopenia and anemia occurred in 78% , 36% and 27% of the cycles administered, respectively) and 1.8% fatal acute toxicities were reported. Moreover of greater concern is the incidence of almost fatal secondary acute leukemia and myelodysplastic syndrome (3 cases in 323 patients). The choice of first-line treatment requires balancing the desire for optimal disease control with the occurrence of early and late treatment-related toxicities. Long-term outcome following an optimal salvage treatment, consisting in high-dose chemotherapy with ASCT should also be taken into consideration. In the present study we plan to compare the efficacy and toxicity of two therapeutic strategies consisting in two different first-line treatments followed by a pre-planned salvage program, when indicated
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 331
- Histologically confirmed, newly diagnosed Hodgkin's lymphoma (pathological review diagnosis available)
- No prior treatment
- Stage II B, III A and B, IV A and B
- Normal hematopoietic function as measured by leucocytes equal to or greater than 3500/mm3, neutrophils equal to or greater than 1500/mm3, platelets equal to or greater than 100000/mm3
- Normal renal function (serum creatinine < 1,5x ULN) and normal liver function (SGOT/SGPT equal to or lower than 2.5x ULN; bilirubin equal to or lower than 1.5x ULN)
- No significant history or current evidence of cardiovascular disease, or major respiratory disease
- No severe neurologic or psychiatric disease
- No other malignancy except basal cell carcinoma of the skin and/or in situ cervical carcinoma of the uterus
- Serological negativity for hepatitis B or C or HIV infection
- ECOG performance status equal to or lower than 2
- Life expectancy of at least three months
- Effective contraception in all patients and a negative pregnancy test for women of childbearing potential
- Written informed consent and consent to a regular follow-up in the outpatient clinic
Exclusion criteria:
- Sever central nervous system or psychiatric disease
- History or current evidence of clinically significant cardiac disease (congestive heart failure, uncontrolled hypertension, unstable coronary artery disease or myocardial infarction or severe arrhythmias. Left ventricular ejection fraction < 50% at rest by echocardiography or < 55% by isotopic measurement
- Serological positivity for HBV, HCV or HIV
- History or current evidence of malignancy other than basal cell carcinoma of the skin, carcinoma in situ of the cervix
- Lactating or pregnant women
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm B Etoposide BEACOPP (Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) for 4 escalated cycles followed by 4 standard cycles Arm B Procarbazine BEACOPP (Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) for 4 escalated cycles followed by 4 standard cycles Arm B Doxorubicin BEACOPP (Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) for 4 escalated cycles followed by 4 standard cycles Arm B Bleomycin BEACOPP (Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) for 4 escalated cycles followed by 4 standard cycles Arm B Vincristine BEACOPP (Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) for 4 escalated cycles followed by 4 standard cycles Arm B Cyclophosphamide BEACOPP (Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) for 4 escalated cycles followed by 4 standard cycles Arm B Prednisone BEACOPP (Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) for 4 escalated cycles followed by 4 standard cycles Arm A Doxorubicin ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for 6 to 8 cycles Arm A Bleomycin ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for 6 to 8 cycles Arm A Vinblastine ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for 6 to 8 cycles Arm A Dacarbazine ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for 6 to 8 cycles
- Primary Outcome Measures
Name Time Method Freedom from first progression at 5 years After a median of 5 years from start of the study
- Secondary Outcome Measures
Name Time Method Number of participants long term sequelae After a median of 10 years Number of participants who developed leukemia Number of participants who developed solid tumors Number of participants who developed cardiovascular disease
Number of participants with acute adverse events at initial therapy and at salvage therapy as a measure of safety and tolerability After 3 months from last intervention Freedom from second progression at 5 years After a median of 5 years from start of protocol Overall survival at 5 years After a median of 5 years from start of the protocol
Trial Locations
- Locations (1)
Fondazione IRCCS Istituto Nazionale di Tumori di Milano
🇮🇹Milano, Italy