Study Comparing ABVD vs BEACOPP in Advanced Hodgkin's Lymphoma

NCT ID: NCT01251107

Last Updated: 2015-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 331 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-03-31
• Study Completion Date: 2009-11-30

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

Conditions

Hodgkin Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm B

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

Group Type: EXPERIMENTAL

Bleomycin

Intervention Type: DRUG

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

Etoposide

Intervention Type: DRUG

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

Doxorubicin

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Vincristine

Intervention Type: DRUG

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

Procarbazine

Intervention Type: DRUG

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

Prednisone

Intervention Type: DRUG

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

Arm A

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

Group Type: ACTIVE_COMPARATOR

Doxorubicin

Intervention Type: DRUG

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

Bleomycin

Intervention Type: DRUG

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

Vinblastine

Intervention Type: DRUG

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

Dacarbazine

Intervention Type: DRUG

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

Interventions

Bleomycin

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

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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

Intervention Type: DRUG

Vincristine

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

Intervention Type: DRUG

Procarbazine

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

Intervention Type: DRUG

Prednisone

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

Intervention Type: DRUG

Doxorubicin

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

Intervention Type: DRUG

Bleomycin

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

Intervention Type: DRUG

Vinblastine

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

Intervention Type: DRUG

Dacarbazine

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

Intervention Type: DRUG

Other Intervention Names

Bleomicina Teva; VP-16, Etoposide Teva; Adriblastina Pfizer; Endoxan Baxter; Vincristina Teva Italia; Natulan; Deltacortene; Adriblastina Pfizer; Bleomicina Teva; Velbe; Dacarbazina Medac

Eligibility 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

• Minimum Eligible Age: 17 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Michelangelo

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alessandro M Gianni, MD

Role: STUDY_CHAIR

Fondazione IRCCS Istituto Nazionale Tumori di Milano

Locations

Fondazione IRCCS Istituto Nazionale di Tumori di Milano

Milan, , Italy

Countries

Italy

References

Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V, Vitolo U, Pulsoni A, Liberati AM, Specchia G, Valagussa P, Rossi A, Zaja F, Pogliani EM, Pregno P, Gotti M, Gallamini A, Rota Scalabrini D, Bonadonna G, Gianni AM; Michelangelo Foundation; Gruppo Italiano di Terapie Innovative nei Linfomi; Intergruppo Italiano Linfomi. ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med. 2011 Jul 21;365(3):203-12. doi: 10.1056/NEJMoa1100340.

Reference Type: DERIVED

PMID: 21774708 (View on PubMed)

Other Identifiers

41/99

Identifier Type: -

Identifier Source: org_study_id