Study Comparing ABVD vs BEACOPP in Advanced Hodgkin's Lymphoma

• ClinicalTrials.gov Identifier: NCT01251107
• Recruitment Status: Completed
• First Posted: December 1, 2010
• Last Update Posted: August 13, 2015
• Sponsor: Fondazione Michelangelo
• Information provided by (Responsible Party): Fondazione Michelangelo

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: 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 (Clinical Trial)
• 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: March 2000
• Actual Primary Completion Date: November 2009
• Actual Study Completion Date: November 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 Name: 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 Name: 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 Name: 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 Name: Endoxan Baxter; Drug: Vincristine; 1.4 mg/m2 iv (max 2 mg) on day 8 during cycles 1 to 8; Other Name: Vincristina Teva Italia; Drug: Procarbazine; 100 mg/m2 po from day 1 to 7 during cycles 1 to 8; Other Name: Natulan; Drug: Prednisone; 40 mg/m2 po from day 1 to 14 during cycles 1 to 8; Other Name: 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 Name: Adriblastina Pfizer; Drug: Bleomycin; 10 mg/m2 iv on days 1 and 15 in each cycle; Other Name: Bleomicina Teva; Drug: Vinblastine; 6 mg/m2 iv on days 1 and 15 in each cycle; Other Name: Velbe; Drug: Dacarbazine; 375 mg/m2 iv on days 1 and 15 in each cycle; Other Name: Dacarbazina Medac

Outcome Measures

Primary Outcome Measures :

1. Freedom from first progression at 5 years [ Time Frame: After a median of 5 years from start of the study ]

Secondary Outcome Measures :

1. Freedom from second progression at 5 years [ Time Frame: After a median of 5 years from start of protocol ]
2. Overall survival at 5 years [ Time Frame: After a median of 5 years from start of the protocol ]
3. Number of participants with acute adverse events at initial therapy and at salvage therapy as a measure of safety and tolerability [ Time Frame: After 3 months from last intervention ]
4. Number of participants long term sequelae [ Time Frame: 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

• Ages Eligible for Study: 17 Years to 60 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Italy

Fondazione IRCCS Istituto Nazionale di Tumori di Milano

Milano, Italy

Sponsors and Collaborators

Fondazione Michelangelo

Investigators

• Study Chair: Alessandro M Gianni, MD; Fondazione IRCCS Istituto Nazionale Tumori di Milano

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Fondazione Michelangelo
• ClinicalTrials.gov Identifier: NCT01251107
• Other Study ID Numbers: 41/99
• First Posted: December 1, 2010
• Last Update Posted: August 13, 2015
• Last Verified: February 2011

Keywords provided by Fondazione Michelangelo:

Hodgkin lymphoma; ABVD; BEACOPP; Salvage high dose chemotherapy

Additional relevant MeSH terms:

Lymphoma; Hodgkin Disease; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Prednisone; Cyclophosphamide; Dacarbazine; Doxorubicin; Liposomal doxorubicin; Etoposide; Etoposide phosphate; Vincristine; Bleomycin; Vinblastine; Procarbazine; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors