Study Comparing ABVD vs BEACOPP in Advanced Hodgkin's Lymphoma

Fondazione Michelangelo

Status and phase

Completed

Phase 3

Conditions

Hodgkin Lymphoma

Treatments

Drug: Procarbazine

Drug: Bleomycin

Drug: Cyclophosphamide

Drug: Dacarbazine

Drug: Etoposide

Drug: Vincristine

Drug: Prednisone

Drug: Vinblastine

Drug: Doxorubicin

Study type

Interventional

Funder types

Other

Identifiers

NCT01251107

41/99

Details and patient eligibility

About

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.

Full 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

Enrollment

331 patients

Sex

All

Ages

17 to 60 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Single Group Assignment

Masking

None (Open label)

331 participants in 2 patient groups

Arm B

Experimental group

Description:

BEACOPP (Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) for 4 escalated cycles followed by 4 standard cycles

Treatment:

Drug: Doxorubicin

Drug: Prednisone

Drug: Vincristine

Drug: Etoposide

Drug: Doxorubicin

Drug: Bleomycin

Drug: Cyclophosphamide

Drug: Procarbazine

Arm A

Active Comparator group

Description: