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

Primary Purpose

Non-Hodgkin's Lymphoma

Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
rituximab
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Hodgkin's Lymphoma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Ospedale Civile Dello Spirito Santo; Divisione Di Ematologia
  • Ospedale Civile; Divisione Di Oncologia
  • Ospedale Oncologico Regionale; U.O. Oncologia Medica Ed Ematologia
  • Ospedale Riuniti; Divisione Di Ematologia
  • A.O.U. Policlinico di Modena-Dipartimento di Medicina Diagnostica, Clinica e di Sanità pubblica
  • Az. Osp. Arcispedale S. Maria Nuova; U.O. Di Ematologia
  • Universita' Degli Studi La Sapienza-Ist.Di Ematologia;Dip. Biotecnologie Cel CELLULARI ED EMATOLOGIA
  • A.O. Spedali Civili Di Brescia-P.O. Spedali Civili;U.O. Ematologia
  • Ospedale Maggiore Di Milano; U.O. Ematologia I - Padiglione Marcora
  • Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
  • Ospedale Civile SS. Antonio E Biagio DI Alessandria; Ematologia
  • Az. Osp. S. Croce Ospedale Generale; Sezione Di Ematologia
  • A.O. Universitaria S. Giovanni Battista-Molinette Di Torino; Ematologia 1
  • Az. Osp. Papardo; Struttura Complessa Di Ematologia
  • Az. Osp. Di Careggi; Divisione Di Ematologia

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

Outcomes

Primary Outcome Measures

Percentage of Participants Remaining Failure-Free After 2 Years From Treatment Start Date
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
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
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
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. The reported data refer to values up to 40 months.
FFS - Percentage of Participants With an Event
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
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
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. Reported data refer to values up to 40 months.
OS - Percentage of Participants With an Event
OS was defined as the time from first dosage of study drug to the date of death from any cause.
OS - Time to Event
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
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. The reported data refer to values up to 40 months.
DFS - Percentage of Participants With an Event
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
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
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. Reported data refer to values up to 40 months.
PFS - Percentage of Participants With an Event
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
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
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
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
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.

Full Information

First Posted
June 14, 2010
Last Updated
June 26, 2017
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT01153971
Brief Title
A Study of Induction and Maintenance Treatment With MabThera (Rituximab) in Patients With Indolent B-Cell Nonfollicular Lymphomas
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
July 20, 2005 (Actual)
Primary Completion Date
September 24, 2010 (Actual)
Study Completion Date
September 24, 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin's Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
47 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
rituximab
Other Intervention Name(s)
MabThera/Rituxan
Intervention Description
1
Primary Outcome Measure Information:
Title
Percentage of Participants Remaining Failure-Free After 2 Years From Treatment Start Date
Description
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.
Time Frame
Month 28
Secondary Outcome Measure Information:
Title
Percentage of Participants Achieving a Best Overall Response of CR, CRu, or PR by Study Phase
Description
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.
Time Frame
Baseline, Months 4, 7 (Induction Phase), 11, 16 (Maintenance Phase),22, 28, 34, and 40(Follow-Up Phase)
Title
Percentage of Participants Achieving a Response by Response Type and Study Phase
Description
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.
Time Frame
Baseline, Months 4, 7, 11, 16, 22, 28, 34, and 40
Title
Failure-Free Survival (FFS), Percentage of Participants Estimated to be Free of Documented Disease Progression, Relapse, or Death
Description
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. The reported data refer to values up to 40 months.
Time Frame
Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Title
FFS - Percentage of Participants With an Event
Description
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.
Time Frame
Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Title
FFS - Time to Event
Description
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.
Time Frame
Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Title
Overall Survival (OS) - Percentage of Participants Estimated to be Alive
Description
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. Reported data refer to values up to 40 months.
Time Frame
Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Title
OS - Percentage of Participants With an Event
Description
OS was defined as the time from first dosage of study drug to the date of death from any cause.
Time Frame
Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40.
Title
OS - Time to Event
Description
Overall survival was defined as the time from first dosage of study drug to the date of death from any cause.
Time Frame
Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40.
Title
Disease-Free Survival (DFS) - Percentage of Participants Estimated to be Disease-Free
Description
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. The reported data refer to values up to 40 months.
Time Frame
Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Title
DFS - Percentage of Participants With an Event
Description
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.
Time Frame
Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40.
Title
DFS - Time to Event
Description
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.
Time Frame
Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40.
Title
Progression-free Survival (PFS) - Percentage of Participants Estimated to Be Progress Free
Description
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. Reported data refer to values up to 40 months.
Time Frame
Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Title
PFS - Percentage of Participants With an Event
Description
Progression-free survival was defined as the time from the date of treatment start to the date of documented disease progression.
Time Frame
Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Title
PFS - Time to Event
Description
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.
Time Frame
Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Title
Duration of Response (DR) - Percentage of Participants Expected to Maintain a Response
Description
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.
Time Frame
Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Title
DR - Percentage of Participants With an Event
Description
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.
Time Frame
Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
Title
DR - Time to Event
Description
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.
Time Frame
Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Chair
Facility Information:
Facility Name
Ospedale Civile Dello Spirito Santo; Divisione Di Ematologia
City
Pescara
State/Province
Abruzzo
ZIP/Postal Code
65100
Country
Italy
Facility Name
Ospedale Civile; Divisione Di Oncologia
City
Pescara
State/Province
Abruzzo
ZIP/Postal Code
65124
Country
Italy
Facility Name
Ospedale Oncologico Regionale; U.O. Oncologia Medica Ed Ematologia
City
Rionero in Vulture
State/Province
Basilicata
ZIP/Postal Code
85028
Country
Italy
Facility Name
Ospedale Riuniti; Divisione Di Ematologia
City
Reggio Calabria
State/Province
Calabria
ZIP/Postal Code
89100
Country
Italy
Facility Name
A.O.U. Policlinico di Modena-Dipartimento di Medicina Diagnostica, Clinica e di Sanità pubblica
City
Modena
State/Province
Emilia-Romagna
ZIP/Postal Code
41100
Country
Italy
Facility Name
Az. Osp. Arcispedale S. Maria Nuova; U.O. Di Ematologia
City
Reggio Emilia
State/Province
Emilia-Romagna
ZIP/Postal Code
42100
Country
Italy
Facility Name
Universita' Degli Studi La Sapienza-Ist.Di Ematologia;Dip. Biotecnologie Cel CELLULARI ED EMATOLOGIA
City
Roma
State/Province
Lazio
ZIP/Postal Code
00161
Country
Italy
Facility Name
A.O. Spedali Civili Di Brescia-P.O. Spedali Civili;U.O. Ematologia
City
Brescia
State/Province
Lombardia
ZIP/Postal Code
25123
Country
Italy
Facility Name
Ospedale Maggiore Di Milano; U.O. Ematologia I - Padiglione Marcora
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20122
Country
Italy
Facility Name
Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20162
Country
Italy
Facility Name
Ospedale Civile SS. Antonio E Biagio DI Alessandria; Ematologia
City
Alessandria
State/Province
Piemonte
ZIP/Postal Code
15121
Country
Italy
Facility Name
Az. Osp. S. Croce Ospedale Generale; Sezione Di Ematologia
City
Cuneo
State/Province
Piemonte
ZIP/Postal Code
12100
Country
Italy
Facility Name
A.O. Universitaria S. Giovanni Battista-Molinette Di Torino; Ematologia 1
City
Torino
State/Province
Piemonte
ZIP/Postal Code
10126
Country
Italy
Facility Name
Az. Osp. Papardo; Struttura Complessa Di Ematologia
City
Messina
State/Province
Sicilia
ZIP/Postal Code
98165
Country
Italy
Facility Name
Az. Osp. Di Careggi; Divisione Di Ematologia
City
Firenze
State/Province
Toscana
ZIP/Postal Code
50135
Country
Italy

12. IPD Sharing Statement

Learn more about this trial

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

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