Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT00992030 |
| Other study ID # |
FM-HD09-01 |
| Secondary ID |
2009-009431-30 |
| Status |
Terminated |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
September 2009 |
| Est. completion date |
March 2019 |
Study information
| Verified date |
July 2019 |
| Source |
Fondazione Michelangelo |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Combined modality therapy has then emerged as the standard of care for limited-stage
Hodgkin's lymphoma and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)
chemotherapy that is devoid of alkylating agents and associated with a low potential for
gonadal toxicity and leukemogenesis, is currently considered a gold standard. Nevertheless,
the disadvantage to combine radiotherapy to ABVD is represented by late cardiovascular events
(myocardial dysfunction and coronary or valvular disease), especially when the heart is
within the radiation field; bleomycin pulmonary toxicity also is increased in conjunction
with RT and secondary tumors, in particular in the RT fields. This study aims at treating
patients with limited disease with multiagent chemotherapy alone, without irradiation, and
using radiotherapy only for relapses.
Description:
Limited-stage Hodgkin lymphoma is a highly curable disease, with expected long-term
disease-free and overall survival rates close to 90% and 95%, respectively. This success has
come at a cost of long-term treatment-related toxicity, such that the patients who live
beyond 10 to 15 years are more likely to die from late complications of treatment than from
the disease itself. In the last decades efforts to improve long-term results have been made
by developing curative strategies aimed to reduce toxicity while maintaining high cure rates.
Based on the observation that systemic chemotherapy can control occult sites of the disease,
thereby eliminating the requirement for staging laparotomy, in the last years the use of
combined modalities that allowed a reduction of number of cycles of chemotherapy and of
radiation field size and doses, thus reducing late toxicity was investigated in various
clinical trials. Combined modality therapy has then emerged as the standard of care for
limited-stage Hodgkin's lymphoma and doxorubicin, bleomycin, vinblastine, and dacarbazine
(ABVD) chemotherapy that is devoid of alkylating agents and associated with a low potential
for gonadal toxicity and leukemogenesis, is currently considered the gold standard.
Nevertheless, optimal treatment is still a question of debate and current investigations are
now taking into consideration to further reduce long-term toxicity. Actually two main options
are available. The first option combines radiotherapy to ABVD chemotherapy, with the aim to
maximize disease control. Using 4 cycles of ABVD followed by involved field radiotherapy at
36 Gy, Bonadonna and coworkers first documented a 94% freedom-from-progression and a 94%
overall survival rate, respectively. The disadvantage with this approach is represented by
late cardiovascular events (myocardial dysfunction and coronary or valvular disease),
especially when the heart is within the radiation field; bleomycin pulmonary toxicity also is
increased in conjunction with RT and secondary tumors, in particular in the RT fields.
Whether these risks will be lower with fewer chemotherapy cycles, lower RT doses, or both has
been studied in many clinical trials that have demonstrated that smaller radiation fields and
lower doses are important, but a key unanswered question is whether RT can be eliminated
completely in limited-stage patients. The second option therefore consists of chemotherapy
with ABVD alone, with the aim to eliminate the late effects of radiotherapy. This approach
have resulted in an absolute increase of the failure rate in the order of 8% (from
approximately 4% up to 12%). However, the majority of relapsing patients achieves a durable
disease control with a second-line radiation-containing combined approach, and shows an
overall survival rate superimposable to that of patients receiving upfront combined strategy
with chemo-radiotherapy. We thus designed a study aimed at treating patients with limited
disease with multiagent chemotherapy alone, without irradiation, and using radiotherapy only
for relapses. In fact, it has recently been reported that the addition of Rituximab (a
monoclonal antibody directed against the CD20 B-cell antigens) to ABVD significantly
increases the antilymphoma activity of ABVD alone in advanced-stage Hodgkin's lymphoma and in
absence of added toxicity. In conclusion, rituximab-supplemented ABVD (R-ABVD) given to
early-stage Hodgkin's lymphoma might represent a radiation-free regimen capable of increasing
long-term disease control of ABVD alone, while avoiding the late effects of radiotherapy.
The primary objective of this study is to evaluate whether the R-ABVD therapy (ARM A) is not
worse than the standard therapy of ABVD-RT (ARM B) in patients with limited Hodgkin's
lymphoma. In this trial a maximum inferiority of 8% of the 3-year Failure Free Survival rate
(FFS) in ARM A with respect to ARM B is considered acceptable to assess that ARM A is not
worse than ARM B.
