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Study Comparing ABVD vs BEACOPP in Advanced Hodgkin's Lymphoma

Primary Purpose

Hodgkin Lymphoma

Status

Completed

Phase

Phase 3

Locations

Italy

Study Type

Interventional

Intervention

Bleomycin

Etoposide

Doxorubicin

Cyclophosphamide

Vincristine

Procarbazine

Prednisone

Doxorubicin

Bleomycin

Vinblastine

Dacarbazine

About this trial

This is an interventional treatment trial for Hodgkin Lymphoma focused on measuring Hodgkin lymphoma, ABVD, BEACOPP, Salvage high dose chemotherapy

Eligibility Criteria

17 Years - 60 Years (Child, Adult)All SexesDoes not accept 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

Sites / Locations

Fondazione IRCCS Istituto Nazionale di Tumori di Milano

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm B

Arm A

Arm Description

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

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

Outcomes

Primary Outcome Measures

Freedom from first progression at 5 years

Secondary Outcome Measures

Freedom from second progression at 5 years

Overall survival at 5 years

Number of participants with acute adverse events at initial therapy and at salvage therapy as a measure of safety and tolerability

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

Full Information

NCT ID

NCT01251107

First Posted

November 26, 2010

Last Updated

August 11, 2015

Sponsor

Fondazione Michelangelo

1. Study Identification

Unique Protocol Identification Number

NCT01251107

Brief Title

Study Comparing ABVD vs BEACOPP in Advanced Hodgkin's Lymphoma

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2011

Overall Recruitment Status

Completed

Study Start Date

March 2000 (undefined)

Primary Completion Date

November 2009 (Actual)

Study Completion Date

November 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Fondazione Michelangelo

4. Oversight

Data Monitoring Committee

5. 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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hodgkin Lymphoma

Keywords

Hodgkin lymphoma, ABVD, BEACOPP, Salvage high dose chemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

331 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm B

Arm Type

Experimental

Arm Description

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

Arm Title

Arm A

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Bleomycin

Other Intervention Name(s)

Bleomicina Teva

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Etoposide

Other Intervention Name(s)

VP-16, Etoposide Teva

Intervention Description

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

Intervention Name(s)

Doxorubicin

Other Intervention Name(s)

Adriblastina Pfizer

Intervention Description

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

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Endoxan Baxter

Intervention Description

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

Intervention Name(s)

Vincristine

Other Intervention Name(s)

Vincristina Teva Italia

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Procarbazine

Other Intervention Name(s)

Natulan

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Prednisone

Other Intervention Name(s)

Deltacortene

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Doxorubicin

Other Intervention Name(s)

Adriblastina Pfizer

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Bleomycin

Other Intervention Name(s)

Bleomicina Teva

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Vinblastine

Other Intervention Name(s)

Velbe

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Dacarbazine

Other Intervention Name(s)

Dacarbazina Medac

Intervention Description

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

Primary Outcome Measure Information:

Title

Freedom from first progression at 5 years

Time Frame

After a median of 5 years from start of the study

Secondary Outcome Measure Information:

Title

Freedom from second progression at 5 years

Time Frame

After a median of 5 years from start of protocol

Title

Overall survival at 5 years

Time Frame

After a median of 5 years from start of the protocol

Title

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

Title

Number of participants long term sequelae

Description

Number of participants who developed leukemia Number of participants who developed solid tumors Number of participants who developed cardiovascular disease

Time Frame

After a median of 10 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

17 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alessandro M Gianni, MD

Organizational Affiliation

Fondazione IRCCS Istituto Nazionale Tumori di Milano

Official's Role

Study Chair

Facility Information:

Facility Name

Fondazione IRCCS Istituto Nazionale di Tumori di Milano

City

Milano

Country

Italy

12. IPD Sharing Statement

Citations:

PubMed Identifier

21774708

Citation

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.

Results Reference

derived

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Study Comparing ABVD vs BEACOPP in Advanced Hodgkin's Lymphoma

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