R-ABVD vs ABVD-RT in Early Stage Hodgkin's Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2011 by Fondazione Michelangelo
Sponsor:
Information provided by (Responsible Party):
Fondazione Michelangelo
ClinicalTrials.gov Identifier:
NCT00992030
First received: October 7, 2009
Last updated: December 21, 2011
Last verified: February 2011
  Purpose

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.


Condition Intervention Phase
Hodgkin Lymphoma
Drug: Rituximab
Radiation: Involved field irradiation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Study Comparing Rituximab-supplemented ABVD (R-ABVD) With ABVD Followed by Involved-field Radiotherapy (ABVD-RT) in Limited Stage (Stage I-IIA With no Areas of Bulk) Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Fondazione Michelangelo:

Primary Outcome Measures:
  • 3-year failure free survival. Failure is defined as disease progression during treatment, achievement of less than complete remission (CR) after the total planned therapy, relapse during follow-up or death from any cause. [ Time Frame: Three-year failure free survival from randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Event-free survival including, besides failures, late serious treatment-related events [ Time Frame: 7 years from randomization ] [ Designated as safety issue: Yes ]
  • Overall survival, all causes included [ Time Frame: 7 year from randomozation ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 336
Study Start Date: September 2009
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ARM A
Rituximab plus ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for 4 cycles
Drug: Rituximab
I.V. infusion weekly x 6 weeks at a dose of 375 mg/m2
Other Names:
  • Drug: rituximab
  • Drug: ABVD regimen
  • Drug: doxorubicin hydrocloride
  • Drug: bleomycin
  • Drug: vinblastine
  • Drug: dacarbazine
Active Comparator: ARM B
ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for 4 cycles followed by involved field irradiation
Radiation: Involved field irradiation
Radiation therapy, limited to initially involved nodal sites, will start within four weeks from the last cycle of ABVD chemotherapy and after complete restaging with TAC total-body and PET total-body. The planned total dose is 30,6 Gy.
Other Names:
  • Drug: ABVD regimen
  • Drug: doxorubicin hydrochloride
  • Drug: bleomycin
  • Drug: vinblastine
  • Drug: dacarbazine
  • Radiation: radiation therapy

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • History of histologically confirmed classical Hodgkin lymphoma (cHL)
  • Limited-stage disease defined as stage I or IIA with no areas of bulky disease
  • Measurable disease according to the Cheson criteria
  • Age >=18 years
  • Adequate bone marrow reserve (ANC >= 1,500/uL, Platelet > 100,000/uL)
  • LVEF >= 50% by MUGA scan or echocardiogram
  • Serum creatinine < 2 mg/dl, serum bilirubin < 2 mg/dl, AST or ALT <2x ULN
  • Bi-dimensionally measurable disease
  • Use of effective means of contraception
  • Signed informed consent form

Exclusion Criteria:

  • Lymphocyte predominant HL
  • Prior chemotherapy or radiation therapy
  • Severe pulmonary disease as judged by the PI including COPD and asthma
  • Presence of CNS lymphoma
  • Concomitant malignancies or previous malignancies (exception made for adequately treated basal or squamous cell carcinoma of the skin)
  • Active infection requiring treatment with intravenous therapy
  • Known HIV infection
  • Active hepatitis B or C
  • Pregnancy or lactation and women of child bearing age who are not practicing adequate contraception
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00992030

Contacts
Contact: Alessandro M Gianni, MD -39022390 ext 2352 alessandro.gianni@unimi.it

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Anas Younes, MD    713-792-2860    ayounes@mdanderson.org   
Principal Investigator: Anas Younes, MD         
Italy
Ospedali Riuniti Umberto I Recruiting
Ancona, Italy, 60020
Principal Investigator: Pietro Leoni, MD         
Ospedali Riuniti Active, not recruiting
Bergamo, Italy, 24100
Policlinico S. Orsola Malpighi Active, not recruiting
Bologna, Italy, 40138
Ospedale Roberto Binaghi Recruiting
Cagliari, Italy, 09126
Principal Investigator: Giorgio La Nasa, MD         
Azienda Ospedaliera Vittorio Emanuele Ferrarotto Recruiting
Catania, Italy, 95124
Principal Investigator: Francesco Di Raimondo, MD         
Fondazione IRCCS Istituto Nazionale Tumori Recruiting
Milano, Italy, 20133
Contact: Alessandro M Gianni, MD    +39-02-2390 ext 2532    alessandro.gianni@unimi.it   
Principal Investigator: Alessandro M Gianni, MD         
Sub-Investigator: Simonetta Viviani, MD         
Azienda Ospedaliero Universitaria S. Luigi Gonzaga Recruiting
Orbassano, Italy, 10043
Principal Investigator: Giuseppe Saglio, MD         
Gianpietro Semenzato Recruiting
Padova, Italy, 35128
Contact: Gianpetro Semenzato, MD    +39 049 8212298    g.semenzato@unipd.it   
Principal Investigator: Gianpietro Semenzato, MD         
Ospedali Riuniti Villa Sofia Cervello Recruiting
Palermo, Italy, 90146
Principal Investigator: Katia Patti, MD         
Ospedale San Carlo Recruiting
Potenza, Italy, 85100
Principal Investigator: Attilio Olivieri, MD         
Sponsors and Collaborators
Fondazione Michelangelo
Investigators
Study Chair: Alessandro M Gianni, MD Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
  More Information

No publications provided

Responsible Party: Fondazione Michelangelo
ClinicalTrials.gov Identifier: NCT00992030     History of Changes
Other Study ID Numbers: FM-HD09-01, EudraCT N 2009-009431-30
Study First Received: October 7, 2009
Last Updated: December 21, 2011
Health Authority: Italy: Ethics Committee

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Liposomal doxorubicin
Doxorubicin
Bleomycin
Vinblastine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on September 22, 2014