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
17 Years
60 Years
Both
Hodgkin Lymphoma
Trial Information
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
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
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Freedom from first progression at 5 years
Outcome Time Frame:
After a median of 5 years from start of the study
Safety Issue:
No
Principal Investigator
Alessandro M Gianni, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Fondazione IRCCS Istituto Nazionale Tumori di Milano
Authority:
Italy: Ethics Committee
Study ID:
41/99
NCT ID:
NCT01251107
Start Date:
March 2000
Completion Date:
November 2009
Related Keywords:
- Hodgkin Lymphoma
- Hodgkin lymphoma
- ABVD
- BEACOPP
- Salvage high dose chemotherapy
- Hodgkin Disease
- Lymphoma
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