Hodgkin Lymphoma
Conditions
Keywords
Hodgkin lymphoma, ABVD, BEACOPP, Salvage high dose chemotherapy
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
Interventions
DRUGBleomycin
10 mg/m2 IV day 8 during cycles 1 to 8
DRUGEtoposide
200 mg/m2 iv on days 1 to 3 during cycles 1 to 4; 100 mg/m2 iv on days 1 to 3 during cycles 5 to 8
DRUGDoxorubicin
35 mg/2 iv on day 1 during cycles 1 to 4; 25 mg/m2 iv on day 1 during cycles 5 to 8
DRUGCyclophosphamide
1250 mg/m2 iv on day 1 during cycles 1 to 4; 650 mg/m2 iv on day 1 during cycles 5 to 8
DRUGVincristine
1.4 mg/m2 iv (max 2 mg) on day 8 during cycles 1 to 8
DRUGProcarbazine
100 mg/m2 po from day 1 to 7 during cycles 1 to 8
DRUGPrednisone
40 mg/m2 po from day 1 to 14 during cycles 1 to 8
DRUGVinblastine
6 mg/m2 iv on days 1 and 15 in each cycle
DRUGDacarbazine
375 mg/m2 iv on days 1 and 15 in each cycle
Sponsors
Fondazione Michelangelo
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
17 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Freedom from first progression at 5 years | After a median of 5 years from start of the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival at 5 years | After a median of 5 years from start of the protocol | — |
| 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 | — |
| 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 |
Countries
Italy
Outcome results
None listed