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Trial record 3 of 26 for:    rituximab radiotherapy | Lymphoma | Italy

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

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ClinicalTrials.gov Identifier: NCT00992030
Recruitment Status : Terminated (Low recruitment and difficulty in having study data)
First Posted : October 8, 2009
Last Update Posted : July 16, 2020
Sponsor:
Information provided by (Responsible Party):
Fondazione Michelangelo

Tracking Information
First Submitted Date  ICMJE October 7, 2009
First Posted Date  ICMJE October 8, 2009
Last Update Posted Date July 16, 2020
Study Start Date  ICMJE September 2009
Actual Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 7, 2009)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2009)
  • Event-free survival including, besides failures, late serious treatment-related events [ Time Frame: 7 years from randomization ]
  • Overall survival, all causes included [ Time Frame: 7 year from randomozation ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE R-ABVD vs ABVD-RT in Early Stage Hodgkin's Lymphoma
Official Title  ICMJE 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
Brief 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hodgkin Lymphoma
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • Experimental: ARM A
    Rituximab plus ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for 4 cycles
    Intervention: Drug: Rituximab
  • Active Comparator: ARM B
    ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for 4 cycles followed by involved field irradiation
    Intervention: Radiation: Involved field irradiation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 14, 2020)
112
Original Estimated Enrollment  ICMJE
 (submitted: October 7, 2009)
336
Actual Study Completion Date  ICMJE March 2019
Actual Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00992030
Other Study ID Numbers  ICMJE FM-HD09-01
2009-009431-30 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fondazione Michelangelo
Study Sponsor  ICMJE Fondazione Michelangelo
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Alessandro M Gianni, MD Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
PRS Account Fondazione Michelangelo
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP