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

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

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.

Study Overview

• Status: Completed
• Conditions: Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: rituximab

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Abruzzo
    • Pescara, Abruzzo, Italy, 65100
      • Ospedale Civile Dello Spirito Santo; Divisione Di Ematologia
    • Pescara, Abruzzo, Italy, 65124
      • Ospedale Civile; Divisione Di Oncologia
  • Basilicata
    • Rionero in Vulture, Basilicata, Italy, 85028
      • Ospedale Oncologico Regionale; U.O. Oncologia Medica Ed Ematologia
  • Calabria
    • Reggio Calabria, Calabria, Italy, 89100
      • Ospedale Riuniti; Divisione Di Ematologia
  • Emilia-Romagna
    • Modena, Emilia-Romagna, Italy, 41100
      • A.O.U. Policlinico di Modena-Dipartimento di Medicina Diagnostica, Clinica e di Sanità pubblica
    • Reggio Emilia, Emilia-Romagna, Italy, 42100
      • Az. Osp. Arcispedale S. Maria Nuova; U.O. Di Ematologia
  • Lazio
    • Roma, Lazio, Italy, 00161
      • Universita' Degli Studi La Sapienza-Ist.Di Ematologia;Dip. Biotecnologie Cel CELLULARI ED EMATOLOGIA
  • Lombardia
    • Brescia, Lombardia, Italy, 25123
      • A.O. Spedali Civili Di Brescia-P.O. Spedali Civili;U.O. Ematologia
    • Milano, Lombardia, Italy, 20122
      • Ospedale Maggiore Di Milano; U.O. Ematologia I - Padiglione Marcora
    • Milano, Lombardia, Italy, 20162
      • Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
  • Piemonte
    • Alessandria, Piemonte, Italy, 15121
      • Ospedale Civile SS. Antonio E Biagio DI Alessandria; Ematologia
    • Cuneo, Piemonte, Italy, 12100
      • Az. Osp. S. Croce Ospedale Generale; Sezione Di Ematologia
    • Torino, Piemonte, Italy, 10126
      • A.O. Universitaria S. Giovanni Battista-Molinette Di Torino; Ematologia 1
  • Sicilia
    • Messina, Sicilia, Italy, 98165
      • Az. Osp. Papardo; Struttura Complessa Di Ematologia
  • Toscana
    • Firenze, Toscana, Italy, 50135
      • Az. Osp. Di Careggi; Divisione Di Ematologia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: rituximab; 1; Other Names: MabThera/Rituxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Month 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Months 4, 7 (Induction Phase), 11, 16 (Maintenance Phase),22, 28, 34, and 40(Follow-Up Phase)
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.	Baseline, Months 4, 7, 11, 16, 22, 28, 34, and 40
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.	Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
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.	Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
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.	Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
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.	Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
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.	Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40.
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.	Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40.
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.	Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
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.	Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40.
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.	Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40.
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.	Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
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.	Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
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.	Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
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.	Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
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.	Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40
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.	Baseline, Months 1-8, 10-12, 14, 16, 22, 28, 34 and 40

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2005
• Primary Completion (Actual): September 24, 2010
• Study Completion (Actual): September 24, 2010

Study Registration Dates

• First Submitted: June 14, 2010
• First Submitted That Met QC Criteria: June 29, 2010
• First Posted (Estimate): June 30, 2010

Study Record Updates

• Last Update Posted (Actual): August 1, 2017
• Last Update Submitted That Met QC Criteria: June 26, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: ML18324

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No