Study Comparing ABVD vs BEACOPP in Advanced Hodgkin's Lymphoma

Sponsor

Fondazione Michelangelo (Other)

Overall Status

Completed

CT.gov ID

NCT01251107

Collaborator

(none)

331

Enrollment

Location

Arms

116

Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hodgkin Lymphoma	Drug: Bleomycin Drug: Etoposide Drug: Doxorubicin Drug: Cyclophosphamide Drug: Vincristine Drug: Procarbazine Drug: Prednisone Drug: Doxorubicin Drug: Bleomycin Drug: Vinblastine Drug: Dacarbazine	Phase 3

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

Study Design

Study Type:

Interventional

Actual Enrollment :

331 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2000

Actual Primary Completion Date :

Nov 1, 2009

Actual Study Completion Date :

Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm B BEACOPP (Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) for 4 escalated cycles followed by 4 standard cycles	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
Active Comparator: Arm A ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for 6 to 8 cycles	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

Intervention/Treatment

Experimental: Arm B

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

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

Active Comparator: Arm A

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

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

Outcome Measures

Primary Outcome Measures

Freedom from first progression at 5 years [After a median of 5 years from start of the study]

Secondary Outcome Measures

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]
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]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

17 Years to 60 Years

Sexes Eligible for Study:

All

Accepts 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