Trial | NCT01251107  Report issue

Title

Study Comparing ABVD vs BEACOPP in Advanced Hodgkin's Lymphoma
Prospective Randomized Comparison of ABVD Versus BEACOPP Chemotherapy With or Without Radiotherapy for Advanced Stage or Unfavorable Hodgkin's Lymphoma (HL)

  • Phase

    Phase 3

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Study Participants

    331
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.
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
Study Started
Mar 31
2000
Primary Completion
Nov 30
2009
Study Completion
Nov 30
2009
Last Update
Aug 13
2015
Estimate

Drug Bleomycin

10 mg/m2 IV day 8 during cycles 1 to 8

  • Other names: Bleomicina Teva

Drug Etoposide

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

  • Other names: VP-16, Etoposide Teva

Drug Doxorubicin

35 mg/2 iv on day 1 during cycles 1 to 4; 25 mg/m2 iv on day 1 during cycles 5 to 8

  • Other names: Adriblastina Pfizer

Drug Cyclophosphamide

1250 mg/m2 iv on day 1 during cycles 1 to 4; 650 mg/m2 iv on day 1 during cycles 5 to 8

  • Other names: Endoxan Baxter

Drug Vincristine

1.4 mg/m2 iv (max 2 mg) on day 8 during cycles 1 to 8

  • Other names: Vincristina Teva Italia

Drug Procarbazine

100 mg/m2 po from day 1 to 7 during cycles 1 to 8

  • Other names: Natulan

Drug Prednisone

40 mg/m2 po from day 1 to 14 during cycles 1 to 8

  • Other names: Deltacortene

Drug Doxorubicin

25 mg/m2 iv on days 1 and 15 in each cycle

  • Other names: Adriblastina Pfizer

Drug Bleomycin

10 mg/m2 iv on days 1 and 15 in each cycle

  • Other names: Bleomicina Teva

Drug Vinblastine

6 mg/m2 iv on days 1 and 15 in each cycle

  • Other names: Velbe

Drug Dacarbazine

375 mg/m2 iv on days 1 and 15 in each cycle

  • Other names: Dacarbazina Medac

Arm B Experimental

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

Arm A Active Comparator

ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for 6 to 8 cycles

Criteria 

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
No Results Posted