A Study of Induction and Maintenance Treatment With MabThera (Rituximab) in Patients With Indolent B-Cell Nonfollicular Lymphomas

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01153971
First received: June 14, 2010
Last updated: August 4, 2014
Last verified: August 2014
  Purpose

This study will evaluate the efficacy and safety of MabThera in combination chemotherapy, followed by maintenance treatment with MabThera. The anticipated time on study treatment is 1-2 years, and the target sample size is <100 individuals.


Condition Intervention Phase
Non-Hodgkin's Lymphoma
Drug: rituximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Study of Fludarabine and Cyclophosphamide Plus MabThera Followed by Maintenance With MabThera on Failure-free Survival in Treatment-naïve Patients With Advanced Indolent B-cell Nonfollicular Lymphoma

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants Remaining Failure-Free After 2 Years From Treatment Start Date [ Time Frame: Month 28 ] [ Designated as safety issue: No ]
    Percentage of participants who at 2 years from the start of treatment remained free from documented disease progression, relapse, or death. Failure status was based on tumor evaluation performed on Month 28. Participants who did not have a tumor evaluation at Month 28 were counted as failures.


Secondary Outcome Measures:
  • Percentage of Participants Achieving a Best Overall Response of CR, CRu, or PR by Study Phase [ Time Frame: Baseline, Months 4, 7, 11, 16, 22, 28, 34, and 40 ] [ Designated as safety issue: No ]
    CR: complete disappearance of all symptoms/objective signs of disease (enlarged lymph nodes, hepatomegaly, splenomegaly) for at least 3 months following definitive re-evaluation at end of therapy. For initial bone marrow involvement, clearance of bone marrow documented by biopsy, normalization of blood counts with granulocytes greater than (>)1,500 per microliter (/µL), hemoglobin >12 grams per deciliter (g/dL), platelets >100,000/µL. CRu: disappearance of all symptoms and nearly all measurable lesions, but persistence of some radiologic abnormalities with normalization of all biologic abnormalities; normalization of the performance status for at least 3 months after the definite evaluation of therapy. PR: at least 50 percent (%) reduction of measurable and evaluable lymphoma involvement for at least 4 weeks without occurrence of new manifestations, normalization of blood counts. Participants without evaluation at end of induction/maintenance phase were considered nonresponders.

  • Percentage of Participants Achieving a Response by Response Type and Study Phase [ Time Frame: Baseline, Months 4, 7, 11, 16, 22, 28, 34, and 40 ] [ Designated as safety issue: No ]
    CR: complete disappearance of all symptoms/objective signs of disease (enlarged lymph nodes, hepatomegaly, splenomegaly) for at least 3 months following definitive re-evaluation at end of therapy. For initial bone marrow involvement, clearance of bone marrow documented by biopsy, normalization of blood counts with granulocytes greater than (>)1,500 per microliter (/µL), hemoglobin >12 grams per deciliter (g/dL), platelets >100,000/µL. CRu: disappearance of all symptoms and nearly all measurable lesions, but persistence of some radiologic abnormalities with normalization of all biologic abnormalities; normalization of the performance status for at least 3 months after the definite evaluation of therapy. PR: at least 50 percent (%) reduction of measurable and evaluable lymphoma involvement for at least 4 weeks without occurrence of new manifestations, normalization of blood counts. Participants without evaluation at end of induction/maintenance phase were considered nonresponders.

  • Failure-Free Survival (FFS), Percentage of Participants Estimated to be Free of Documented Disease Progression, Relapse, or Death [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 ] [ Designated as safety issue: No ]
    FFS data were analyzed using Kaplan-Meier survival analysis. FFS was measured from the date of treatment start to the date of documented disease progression, relapse, or death from any cause. Responding participants, participants who were lost to follow up, who withdrew consent, or dropped out due to adverse events (AE) were censored at their last assessment date.

  • FFS - Percentage of Participants With an Event [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 ] [ Designated as safety issue: No ]
    FFS was measured from the date of treatment start to the date of documented disease progression, relapse, or death from any cause. Responding participants, participants who were lost to follow up, who withdrew consent, or who dropped out due to AEs were censored at their last assessment date.

  • FFS - Time to Event [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 ] [ Designated as safety issue: No ]

    FFS was measured from the date of treatment start to the date of documented disease progression, relapse or death from any cause. Responding participants, participants who were lost to follow up, who withdrew consent or dropped out due to AEs were censored at their last assessment date.

    NOTE: The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.


  • Overall Survival (OS) - Percentage of Participants Estimated to be Alive [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 ] [ Designated as safety issue: No ]
    OS data were analyzed using Kaplan-Meier survival analysis. OS was defined as the time from first dosage of study drug to the date of death from any cause.

  • OS - Percentage of Participants With an Event [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40. ] [ Designated as safety issue: No ]
    OS was defined as the time from first dosage of study drug to the date of death from any cause.

  • OS - Time to Event [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40. ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from first dosage of study drug to the date of death from any cause.

  • Disease-Free Survival (DFS) - Percentage of Participants Estimated to be Disease-Free [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 ] [ Designated as safety issue: No ]
    DFS data were analyzed using Kaplan-Meier survival analysis. DFS was defined for all participants who achieved a complete response (CR/CRu) at month 1 after the completion of treatment of the induction phase (Month 7 of the study) and was measured from the time of CR to the date of relapse. Participants without relapse were censored at their last assessment date. Participants who died due to tumour burden were considered in relapse. Participants who died due to any other causes were censored as of the death date.

  • DFS - Percentage of Participants With an Event [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40. ] [ Designated as safety issue: No ]
    DFS was defined for all patients who achieved a complete response (CR/CRu) at month 1 after the completion of treatment of the induction phase (month 7 of the study) and was measured from the time of complete response to the date of relapse. Participants without relapse were censored at their last assessment date. Participants who died due to tumour burden were considered in relapse. Participants who died due to any other causes were censored on the death date.

  • DFS - Time to Event [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40. ] [ Designated as safety issue: No ]

    DFS was defined for all participants who achieved a complete response (CR/CRu) at month 1 after the completion of treatment of the induction phase (month 7 of the study) and was measured from the time of complete response to the date of relapse. Participants without relapse were censored at their last assessment date. Participants who died due to tumour burden were considered in relapse. Participants who died due to any other causes were censored on the death date.

    NOTE: The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.


  • Progression-free Survival (PFS) - Percentage of Participants Estimated to Be Progress Free [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 ] [ Designated as safety issue: No ]
    PFS data were analyzed using Kaplan-Meier survival analysis. PFS was defined as the time from treatment start to the date of documented disease progression.

  • PFS - Percentage of Participants With an Event [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 ] [ Designated as safety issue: No ]
    Progression-free survival was defined as the time from the date of treatment start to the date of documented disease progression.

  • PFS - Time to Event [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 ] [ Designated as safety issue: No ]

    Progression-free survival was defined as the time from treatment start to the date of documented disease progression.

    NOTE: The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.


  • Duration of Response (DR) - Percentage of Participants Expected to Maintain a Response [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 ] [ Designated as safety issue: No ]
    DR data were analyzed using Kaplan-Meier survival analysis. DR was defined for all participants who achieved a response (CR, CRu and PR) at month 1 after the completion of treatment of the induction phase (Month 7 of the study) and was measured from the time of response until the date of progression or relapse. Participants without relapse or progression were censored at their last assessment date. Participants who died due to tumour were considered in progression. Participants who died for any other cause were censored to the death date.

  • DR - Percentage of Participants With an Event [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 ] [ Designated as safety issue: No ]
    DR was defined for all participants who achieved a response (CR, CRu and PR) at month 1 after the completion of treatment of the induction phase (Month 7 of the study) and was measured from the time of response until the date of progression or relapse. Participants without relapse or progression were censored at their last assessment date. Participants who died due to tumour were considered in progression. Participants who died for any other cause were censored to the death date.

  • DR - Time to Event [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 ] [ Designated as safety issue: No ]
    DR was defined for all participants who achieved a response (CR, CRu and PR) at month 1 after the completion of treatment of the induction phase (Month 7 of the study) and was measured from the time of response until the date of progression or relapse. Participants without relapse or progression were censored at their last assessment date. Participants who died due to tumour were considered in progression. Participants who died for any other cause were censored to the death date.


Enrollment: 47
Study Start Date: July 2005
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: rituximab
1
Other Name: MabThera/Rituxan

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients 18-65 years of age;
  • previously untreated indolent nonfollicular non-Hodgkin's lymphoma;
  • active disease;
  • >=3 involved sites.

Exclusion Criteria:

  • typical chronic lymphocytic leukemia;
  • other malignancies within 3 years before study, except basal or squamous cell skin cancer or cancer in situ of the cervix;
  • systemic corticosteroid use for >1 month;
  • significant cardiovascular disease;
  • central nervous system involvement;
  • hepatitis B or C virus infection, or HIV infection.
  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: NCT01153971

Locations
Italy
Alessandria, Italy, 15100
Brescia, Italy, 25123
Cuneo, Italy, 12100
Firenze, Italy, 50135
Messina, Italy, 98165
Milano, Italy, 20122
Milano, Italy, 20162
Modena, Italy, 41100
Pescara, Italy, 65124
Pescara, Italy, 65100
Reggio Calabria, Italy, 89100
Reggio Emilia, Italy, 42100
Rionero in Vulture, Italy, 85028
Roma, Italy, 00161
Torino, Italy, 10126
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Chair: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01153971     History of Changes
Other Study ID Numbers: ML18324
Study First Received: June 14, 2010
Results First Received: August 4, 2014
Last Updated: August 4, 2014
Health Authority: Italy: Ministry of Health

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 28, 2014