Study Comparing ABVD vs BEACOPP in Advanced Hodgkin's Lymphoma

August 11, 2015 updated by: Fondazione Michelangelo

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

331

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milano, Italy
        • Fondazione IRCCS Istituto Nazionale di Tumori di Milano

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

17 years to 60 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Endoxan Baxter
Drug: Vincristine
1.4 mg/m2 iv (max 2 mg) on day 8 during cycles 1 to 8
Other Names:
  • Vincristina Teva Italia
Drug: Procarbazine
100 mg/m2 po from day 1 to 7 during cycles 1 to 8
Other Names:
  • Natulan
Drug: Prednisone
40 mg/m2 po from day 1 to 14 during cycles 1 to 8
Other Names:
  • Deltacortene
Drug: Doxorubicin
25 mg/m2 iv on days 1 and 15 in each cycle
Other Names:
  • Adriblastina Pfizer
Drug: Bleomycin
10 mg/m2 iv on days 1 and 15 in each cycle
Other Names:
  • Bleomicina Teva
ACTIVE_COMPARATOR: Arm A
ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for 6 to 8 cycles
Drug: Bleomycin
10 mg/m2 IV day 8 during cycles 1 to 8
Other Names:
  • Bleomicina 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 Names:
  • Adriblastina Pfizer
Drug: Doxorubicin
25 mg/m2 iv on days 1 and 15 in each cycle
Other Names:
  • Adriblastina Pfizer
Drug: Bleomycin
10 mg/m2 iv on days 1 and 15 in each cycle
Other Names:
  • Bleomicina Teva
Drug: Vinblastine
6 mg/m2 iv on days 1 and 15 in each cycle
Other Names:
  • Velbe
Drug: Dacarbazine
375 mg/m2 iv on days 1 and 15 in each cycle
Other Names:
  • Dacarbazina Medac

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Freedom from first progression at 5 years
Time Frame: After a median of 5 years from start of the study
After a median of 5 years from start of the study

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Freedom from second progression at 5 years
Time Frame: After a median of 5 years from start of protocol
After a median of 5 years from start of protocol
Overall survival at 5 years
Time Frame: After a median of 5 years from start of the protocol
After a median of 5 years from start of the protocol
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
After 3 months from last intervention
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
After a median of 10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Michelangelo

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2000

Primary Completion (ACTUAL)

November 1, 2009

Study Completion (ACTUAL)

November 1, 2009

Study Registration Dates

First Submitted

November 26, 2010

First Submitted That Met QC Criteria

November 30, 2010

First Posted (ESTIMATE)

December 1, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

August 13, 2015

Last Update Submitted That Met QC Criteria

August 11, 2015

Last Verified

February 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 41/99

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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