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

• ClinicalTrials.gov Identifier: NCT01153971
• Recruitment Status: Completed
• First Posted: June 30, 2010
• Results First Posted: August 21, 2014
• Last Update Posted: August 1, 2017
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

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.

Condition or disease	Intervention/treatment	Phase
Non-Hodgkin's Lymphoma	Drug: rituximab	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 47 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Actual Study Start Date: July 20, 2005
• Actual Primary Completion Date: September 24, 2010
• Actual Study Completion Date: September 24, 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1	Drug: rituximab; 1; Other Name: MabThera/Rituxan

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants Remaining Failure-Free After 2 Years From Treatment Start Date [ Time Frame: Month 28 ]
   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 :

1. Percentage of Participants Achieving a Best Overall Response of CR, CRu, or PR by Study Phase [ Time Frame: Baseline, Months 4, 7 (Induction Phase), 11, 16 (Maintenance Phase),22, 28, 34, and 40(Follow-Up 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.
2. 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 ]
   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.
3. 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 ]
   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.
4. FFS - Percentage of Participants With an Event [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 ]
   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.
5. FFS - Time to Event [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 ]
   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.
6. 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 ]
   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.
7. OS - Percentage of Participants With an Event [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40. ]
   OS was defined as the time from first dosage of study drug to the date of death from any cause.
8. OS - Time to Event [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40. ]
   Overall survival was defined as the time from first dosage of study drug to the date of death from any cause.
9. 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 ]
   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.
10. DFS - Percentage of Participants With an Event [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40. ]
    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.
11. DFS - Time to Event [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40. ]
    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.
12. 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 ]
    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.
13. PFS - Percentage of Participants With an Event [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 ]
    Progression-free survival was defined as the time from the date of treatment start to the date of documented disease progression.
14. PFS - Time to Event [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 ]
    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.
15. 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 ]
    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.
16. DR - Percentage of Participants With an Event [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 ]
    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.
17. DR - Time to Event [ Time Frame: Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40 ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

Italy

Ospedale Civile Dello Spirito Santo; Divisione Di Ematologia

Pescara, Abruzzo, Italy, 65100

Ospedale Civile; Divisione Di Oncologia

Pescara, Abruzzo, Italy, 65124

Ospedale Oncologico Regionale; U.O. Oncologia Medica Ed Ematologia

Rionero in Vulture, Basilicata, Italy, 85028

Ospedale Riuniti; Divisione Di Ematologia

Reggio Calabria, Calabria, Italy, 89100

A.O.U. Policlinico di Modena-Dipartimento di Medicina Diagnostica, Clinica e di Sanità pubblica

Modena, Emilia-Romagna, Italy, 41100

Az. Osp. Arcispedale S. Maria Nuova; U.O. Di Ematologia

Reggio Emilia, Emilia-Romagna, Italy, 42100

Universita' Degli Studi La Sapienza-Ist.Di Ematologia;Dip. Biotecnologie Cel CELLULARI ED EMATOLOGIA

Roma, Lazio, Italy, 00161

A.O. Spedali Civili Di Brescia-P.O. Spedali Civili;U.O. Ematologia

Brescia, Lombardia, Italy, 25123

Ospedale Maggiore Di Milano; U.O. Ematologia I - Padiglione Marcora

Milano, Lombardia, Italy, 20122

Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia

Milano, Lombardia, Italy, 20162

Ospedale Civile SS. Antonio E Biagio DI Alessandria; Ematologia

Alessandria, Piemonte, Italy, 15121

Az. Osp. S. Croce Ospedale Generale; Sezione Di Ematologia

Cuneo, Piemonte, Italy, 12100

A.O. Universitaria S. Giovanni Battista-Molinette Di Torino; Ematologia 1

Torino, Piemonte, Italy, 10126

Az. Osp. Papardo; Struttura Complessa Di Ematologia

Messina, Sicilia, Italy, 98165

Az. Osp. Di Careggi; Divisione Di Ematologia

Firenze, Toscana, Italy, 50135

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Chair: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01153971
• Other Study ID Numbers: ML18324
• First Posted: June 30, 2010
• Results First Posted: August 21, 2014
• Last Update Posted: August 1, 2017
• Last Verified: June 2017

Additional relevant MeSH terms:

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Rituximab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents