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Study Comparing Doxorubicin, Bleomycin,Vinblastine, Dacarbazine (ABVD) vs Bleomycin, Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine and Prednisone (BEACOPP)

This study has been completed.
Sponsor:
Information provided by:
Fondazione Michelangelo
ClinicalTrials.gov Identifier:
NCT01251107
First received: November 26, 2010
Last updated: February 4, 2011
Last verified: February 2011
  Purpose

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 Intervention Phase
Hodgkin Lymphoma
Drug: Bleomycin
Drug: Etoposide
Drug: Doxorubicin
Drug: Cyclophosphamide
Drug: Vincristine
Drug: Procarbazine
Drug: Prednisone
Drug: Vinblastine
Drug: Dacarbazine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prospective Randomized Comparison of ABVD Versus BEACOPP Chemotherapy With or Without Radiotherapy for Advanced Stage or Unfavorable (IPS Equal or Greater Than 3) Hodgkin's Lymphoma (HL), Immediately Followed by Salvage High-dose Chemotherapy in Refractory or Relapsed Patients

Resource links provided by NLM:


Further study details as provided by Fondazione Michelangelo:

Primary Outcome Measures:
  • Freedom from first progression at 5 years [ Time Frame: After a median of 5 years from start of the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Freedom from second progression at 5 years [ Time Frame: After a median of 5 years from start of protocol ] [ Designated as safety issue: No ]
  • Overall survival at 5 years [ Time Frame: After a median of 5 years from start of the protocol ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Number of participants long term sequelae [ Time Frame: After a median of 10 years ] [ Designated as safety issue: Yes ]
    Number of participants who developed leukemia Number of participants who developed solid tumors Number of participants who developed cardiovascular disease


Enrollment: 331
Study Start Date: March 2000
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
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
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
Drug: Vincristine
1.4 mg/m2 iv (max 2 mg) on day 8 during cycles 1 to 8
Drug: Procarbazine
100 mg/m2 po from day 1 to 7 during cycles 1 to 8
Drug: Prednisone
40 mg/m2 po from day 1 to 14 during cycles 1 to 8
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
Drug: Bleomycin
10 mg/m2 iv on days 1 and 15 in each cycle
Drug: Vinblastine
6 mg/m2 iv on days 1 and 15 in each cycle
Drug: Dacarbazine
375 mg/m2 iv on days 1 and 15 in each cycle

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

  Eligibility

Ages Eligible for Study:   17 Years to 60 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01251107

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

No publications provided by Fondazione Michelangelo

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pinuccia Valagussa, Fondazione Michelangelo
ClinicalTrials.gov Identifier: NCT01251107     History of Changes
Other Study ID Numbers: 41/99
Study First Received: November 26, 2010
Last Updated: February 4, 2011
Health Authority: Italy: Ethics Committee

Keywords provided by Fondazione Michelangelo:
Hodgkin lymphoma
ABVD
BEACOPP
Salvage high dose chemotherapy

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Bleomycin
Cyclophosphamide
Doxorubicin
Etoposide
Etoposide phosphate
Liposomal doxorubicin
Prednisone
Procarbazine
Vinblastine
Vincristine
Alkylating Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on November 20, 2014