Study Comparing ABVD vs BEACOPP in Advanced Hodgkin's Lymphoma

Hodgkin Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01251107
• Other study ID #: 41/99
• Status: Completed
• Phase: Phase 3
• First received: November 26, 2010
• Last updated: August 11, 2015
• Start date: March 2000
• Est. completion date: November 2009

Study information

• Verified date: February 2011
• Source: Fondazione Michelangelo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 331
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 17 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin Lymphoma
• Lymphoma

Intervention

Drug:
• Bleomycin
10 mg/m2 IV day 8 during cycles 1 to 8
• 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
• 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
• 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
• Vincristine
1.4 mg/m2 iv (max 2 mg) on day 8 during cycles 1 to 8
• Procarbazine
100 mg/m2 po from day 1 to 7 during cycles 1 to 8
• Prednisone
40 mg/m2 po from day 1 to 14 during cycles 1 to 8
• Doxorubicin
25 mg/m2 iv on days 1 and 15 in each cycle
• Bleomycin
10 mg/m2 iv on days 1 and 15 in each cycle
• Vinblastine
6 mg/m2 iv on days 1 and 15 in each cycle
• Dacarbazine
375 mg/m2 iv on days 1 and 15 in each cycle

Locations

Country	Name	City	State
Italy	Fondazione IRCCS Istituto Nazionale di Tumori di Milano	Milano

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Michelangelo

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Freedom from first progression at 5 years		After a median of 5 years from start of the study	No
Secondary	Freedom from second progression at 5 years		After a median of 5 years from start of protocol	No
Secondary	Overall survival at 5 years		After a median of 5 years from start of the protocol	No
Secondary	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	Yes
Secondary	Number of participants long term sequelae	Number of participants who developed leukemia Number of participants who developed solid tumors Number of participants who developed cardiovascular disease	After a median of 10 years	Yes