Back to resultsA Study of MabThera/Rituxan (Rituximab) Alone and in Combination With Roferon-A in Patients With Follicular or Other CD20+ Low-Grade (Indolent) Lymphoma
Primary Purpose
Lymphoma
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
rituximab
interferon-a-2a
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma
Eligibility Criteria
Inclusion Criteria:
- Adult patients >18 years of age
- CD20+ low-grade (indolent) lymphoma of follicular and marginal zone type, small lymphocytic lymphoma without a B-CLL phenotype, or indolent lymphoma not otherwise specified
- Stage II (with bulky disease), III, or IV lymphoma
- No previous chemotherapy or a maximum of 6 months chlorambucil or cyclophosphamide
- Indication for treatment: symptomatic enlarged lymph nodes, spleen or other lymphoma manifestations, progression >6 months of lymphadenopathy or splenomegaly, anemia or thrombocytopenia or decreased hemoglobin or platelets due to lymphoma, general symptoms (weight loss, night sweats or fever)
- WHO performance status 0-2
Exclusion Criteria:
- Prior treatment with rituximab or an interferon
- B-CLL, mantle cell lymphoma, lymphoplasmacytic lymphoma (Waldenstroem's disease), or central nervous system lymphoma
- Indolent lymphoma transformed into aggressive lymphoma
- Indolent lymphoma with bulky tumor requiring urgent therapy
- Prior malignancies, except non-melanoma skin tumors, in situ cervical cancer, or curative surgery >5 years ago
- Positive for HIV infection
- Uncontrolled asthma or allergy requiring corticosteroids
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Rituximab Monotherapy
Rituximab, Interferon
Arm Description
Participants received 375 milligrams per square meter (mg/m2) rituximab intravenously (i.v.) weekly for 4 weeks. Participants achieving minor response (MR), partial response (PR), or completer response (CR) received a second cycle of treatment.
Participants received 375 mg/m2 rituximab i.v. weekly for 4 weeks; and 3 million international units per day (MIU/day) interferon-a2a subcutaneously (s.c.) during Week 1, and 4.5 MIU/day s.c. 6 days per week during Weeks 2 through 5. Interferon-a2a was not administered on days of rituximab administration. Participants achieving MR, PR, or CR received a second cycle of treatment.
Outcomes
Primary Outcome Measures
Treatment Failure - Percentage of Participants With an Event
Treatment failure was defined as an event of any of the following: progressive disease while receiving study treatment, death due to any cause, or the initiation of another type of treatment due to stable disease, progressive disease or relapse, or intolerance to study treatment.
Treatment Failure - Time to Event
The median time, in months, between randomization and treatment failure event determined using Kaplan-Meier estimates.
Secondary Outcome Measures
Percentage of Participants Achieving Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR)
CR was defined as the complete disappearance of all previously detectable disease signs; the absence of palpable lymph nodes greater than (>) 1 centimeter (cm) or nodes >1.5 cm observed in computerized axial tomography (CAT) scan; and negative bone marrow pathology, if initially positive. CRu was defined as CR, except that bone marrow results were indeterminate. PR was defined as a decrease of greater than or equal to (≥) 50 percent (%) compared with the BL value in the sum of the products of the two largest perpendicular diameters in all measurable and evaluable lesions; and a ≥50% reduction of the size from BL if hepato-splenomegaly was present.
Percentage of Participants Achieving CR or CRu
CR was defined as the complete disappearance of all previously detectable disease signs; the absence of palpable lymph nodes >1 cm or nodes >1.5 cm observed in CATscan; and negative bone marrow pathology, if initially positive. CRu was defined as CR, except that bone marrow results were indeterminate.
Duration of Response - Percentage of Participants With an Event
Response duration was defined as the period between the date for first observation of CR, CRu or PR and the date of progressive disease (PD), censored observation or death of any cause. Response duration was also assessed for response defined as CR only. Response duration was calculated among responders (CR+CRu+PR) with cutoffs for follow-up applied.
Duration of Response
The median time, in months, from the date of the first observation of CR, CRu, or PR and the date of progressive disease (PD), censored observation, or death due to any cause. PD was defined as an increase of >50% compared to BL in the sum of the product of the two largest perpendicular parameters of measurable lymphoma, or the occurrence of new lesions. One month=30.4 days. Response duration was calculated amongst responders (CR+CRu+PR) with cutoffs for follow-up applied.
Disease Progression - Percentage of Participants With an Event
A disease progression event was defined as tumor progression or death due to any cause (or a censored observation).
Time to Disease Progression
The median time, in months, from randomization to disease progression event assessed using Kaplan-Meier estimates. One month=30.4 days
Overall Survival (OS) - Percentage of Participants With an Event
An overall survival event was defined as death due to any cause.
Overall Survival
The median time, in months, from randomization to OS event assessed using Kaplan-Meier estimates. One month=30.4 days
Full Information
NCT ID
NCT01609010
First Posted
May 29, 2012
Last Updated
August 29, 2014
Sponsor
Hoffmann-La Roche
Collaborators
Nordic Lymphoma Group
1. Study Identification
Unique Protocol Identification Number
NCT01609010
Brief Title
A Study of MabThera/Rituxan (Rituximab) Alone and in Combination With Roferon-A in Patients With Follicular or Other CD20+ Low-Grade (Indolent) Lymphoma
Official Title
Rituximab (Mabthera®) as Single Agent and in Combination With Interferon Alfa-2a (Roferon-A®), a Phase-III Randomized Trial in Patients With Follicular or Other CD20+ Low-grade (Indolent) Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
October 2002 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
July 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
Collaborators
Nordic Lymphoma Group
4. Oversight
5. Study Description
Brief Summary
This randomized, open-label study will compare the efficacy and safety of MabThera/Rituxan (rituximab) alone, and in combination with Roferon-A (interferon alfa-2a) in patients with follicular or other CD20+ low-grade lymphoma. Patients will be randomized to receive either MabThera/Rituxan 375 mg/m2 intravenously weekly for 4 weeks or Roferon-A 3 MIU/day subcutaneously in Week 1 followed by 4.5 MIU/day sc in Weeks 2-5 plus MabThera/Rituxan 375 mg/m2 weekly iv in Weeks 3-6. Patients who have a response will receive an additional cycle of treatment. The anticipated time on study treatment is up to 6 months.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
313 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rituximab Monotherapy
Arm Type
Active Comparator
Arm Description
Participants received 375 milligrams per square meter (mg/m2) rituximab intravenously (i.v.) weekly for 4 weeks. Participants achieving minor response (MR), partial response (PR), or completer response (CR) received a second cycle of treatment.
Arm Title
Rituximab, Interferon
Arm Type
Experimental
Arm Description
Participants received 375 mg/m2 rituximab i.v. weekly for 4 weeks; and 3 million international units per day (MIU/day) interferon-a2a subcutaneously (s.c.) during Week 1, and 4.5 MIU/day s.c. 6 days per week during Weeks 2 through 5. Interferon-a2a was not administered on days of rituximab administration. Participants achieving MR, PR, or CR received a second cycle of treatment.
Intervention Type
Drug
Intervention Name(s)
rituximab
Other Intervention Name(s)
MabThera, Rituxan
Intervention Description
375 mg/m2 rituximab i.v. weekly for 4 weeks
Intervention Type
Drug
Intervention Name(s)
interferon-a-2a
Other Intervention Name(s)
Roferon-A
Intervention Description
3 MIU/day interferon-a2a s.c. during Week 1, and 4.5 MIU/day s.c. 6 days per week during Weeks 2 through 5
Primary Outcome Measure Information:
Title
Treatment Failure - Percentage of Participants With an Event
Description
Treatment failure was defined as an event of any of the following: progressive disease while receiving study treatment, death due to any cause, or the initiation of another type of treatment due to stable disease, progressive disease or relapse, or intolerance to study treatment.
Time Frame
Baseline (BL), Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
Title
Treatment Failure - Time to Event
Description
The median time, in months, between randomization and treatment failure event determined using Kaplan-Meier estimates.
Time Frame
BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
Secondary Outcome Measure Information:
Title
Percentage of Participants Achieving Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR)
Description
CR was defined as the complete disappearance of all previously detectable disease signs; the absence of palpable lymph nodes greater than (>) 1 centimeter (cm) or nodes >1.5 cm observed in computerized axial tomography (CAT) scan; and negative bone marrow pathology, if initially positive. CRu was defined as CR, except that bone marrow results were indeterminate. PR was defined as a decrease of greater than or equal to (≥) 50 percent (%) compared with the BL value in the sum of the products of the two largest perpendicular diameters in all measurable and evaluable lesions; and a ≥50% reduction of the size from BL if hepato-splenomegaly was present.
Time Frame
Weeks 10 and 16
Title
Percentage of Participants Achieving CR or CRu
Description
CR was defined as the complete disappearance of all previously detectable disease signs; the absence of palpable lymph nodes >1 cm or nodes >1.5 cm observed in CATscan; and negative bone marrow pathology, if initially positive. CRu was defined as CR, except that bone marrow results were indeterminate.
Time Frame
Weeks 10 and 16
Title
Duration of Response - Percentage of Participants With an Event
Description
Response duration was defined as the period between the date for first observation of CR, CRu or PR and the date of progressive disease (PD), censored observation or death of any cause. Response duration was also assessed for response defined as CR only. Response duration was calculated among responders (CR+CRu+PR) with cutoffs for follow-up applied.
Time Frame
BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
Title
Duration of Response
Description
The median time, in months, from the date of the first observation of CR, CRu, or PR and the date of progressive disease (PD), censored observation, or death due to any cause. PD was defined as an increase of >50% compared to BL in the sum of the product of the two largest perpendicular parameters of measurable lymphoma, or the occurrence of new lesions. One month=30.4 days. Response duration was calculated amongst responders (CR+CRu+PR) with cutoffs for follow-up applied.
Time Frame
BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
Title
Disease Progression - Percentage of Participants With an Event
Description
A disease progression event was defined as tumor progression or death due to any cause (or a censored observation).
Time Frame
BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
Title
Time to Disease Progression
Description
The median time, in months, from randomization to disease progression event assessed using Kaplan-Meier estimates. One month=30.4 days
Time Frame
BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
Title
Overall Survival (OS) - Percentage of Participants With an Event
Description
An overall survival event was defined as death due to any cause.
Time Frame
BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
Title
Overall Survival
Description
The median time, in months, from randomization to OS event assessed using Kaplan-Meier estimates. One month=30.4 days
Time Frame
BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult patients >18 years of age
CD20+ low-grade (indolent) lymphoma of follicular and marginal zone type, small lymphocytic lymphoma without a B-CLL phenotype, or indolent lymphoma not otherwise specified
Stage II (with bulky disease), III, or IV lymphoma
No previous chemotherapy or a maximum of 6 months chlorambucil or cyclophosphamide
Indication for treatment: symptomatic enlarged lymph nodes, spleen or other lymphoma manifestations, progression >6 months of lymphadenopathy or splenomegaly, anemia or thrombocytopenia or decreased hemoglobin or platelets due to lymphoma, general symptoms (weight loss, night sweats or fever)
WHO performance status 0-2
Exclusion Criteria:
Prior treatment with rituximab or an interferon
B-CLL, mantle cell lymphoma, lymphoplasmacytic lymphoma (Waldenstroem's disease), or central nervous system lymphoma
Indolent lymphoma transformed into aggressive lymphoma
Indolent lymphoma with bulky tumor requiring urgent therapy
Prior malignancies, except non-melanoma skin tumors, in situ cervical cancer, or curative surgery >5 years ago
Positive for HIV infection
Uncontrolled asthma or allergy requiring corticosteroids
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Chair
Facility Information:
City
Hillerod
ZIP/Postal Code
3400
Country
Denmark
City
København
ZIP/Postal Code
2100
Country
Denmark
City
Roskilde
ZIP/Postal Code
4000
Country
Denmark
City
Bergen
ZIP/Postal Code
5021
Country
Norway
City
Oslo
ZIP/Postal Code
0379
Country
Norway
City
Oslo
ZIP/Postal Code
0407
Country
Norway
City
Stavanger
ZIP/Postal Code
4068
Country
Norway
City
Tromsø
ZIP/Postal Code
9038
Country
Norway
City
Trondheim
ZIP/Postal Code
7000
Country
Norway
City
Eskilstuna
ZIP/Postal Code
63188
Country
Sweden
City
Falun
ZIP/Postal Code
79182
Country
Sweden
City
Goeteborg
ZIP/Postal Code
41685
Country
Sweden
City
Halmstad
ZIP/Postal Code
30185
Country
Sweden
City
Huddinge
ZIP/Postal Code
14186
Country
Sweden
City
Jonkoping
ZIP/Postal Code
55185
Country
Sweden
City
Karlstad
ZIP/Postal Code
65185
Country
Sweden
City
Kristianstad
ZIP/Postal Code
29185
Country
Sweden
City
Linkoeping
ZIP/Postal Code
58185
Country
Sweden
City
Luleå
ZIP/Postal Code
S-971 80
Country
Sweden
City
Lund
ZIP/Postal Code
22185
Country
Sweden
City
Malmoe
ZIP/Postal Code
21401
Country
Sweden
City
Stockholm
ZIP/Postal Code
118 83
Country
Sweden
City
Stockholm
ZIP/Postal Code
17176
Country
Sweden
City
Sundsvall
ZIP/Postal Code
85186
Country
Sweden
City
Uddevalla
ZIP/Postal Code
45180
Country
Sweden
City
Umea
ZIP/Postal Code
90185
Country
Sweden
City
Uppsala
ZIP/Postal Code
75185
Country
Sweden
City
Vaxjo
ZIP/Postal Code
35185
Country
Sweden
City
Visby
ZIP/Postal Code
62184
Country
Sweden
City
Västerås
ZIP/Postal Code
72189
Country
Sweden
City
Örebro
ZIP/Postal Code
701 85
Country
Sweden
12. IPD Sharing Statement
Citations:
PubMed Identifier
25686644
Citation
Kimby E, Ostenstad B, Brown P, Hagberg H, Erlanson M, Holte H, Linden O, Johansson AS, Ahlgren T, Wader K, Wahlin BE, Delabie J, Sundstrom C; Nordic Lymphoma Group (NLG). Two courses of four weekly infusions of rituximab with or without interferon-alpha2a: final results from a randomized phase III study in symptomatic indolent B-cell lymphomas. Leuk Lymphoma. 2015;56(9):2598-607. doi: 10.3109/10428194.2015.1014363. Epub 2015 Mar 11.
Results Reference
derived
Learn more about this trial
A Study of MabThera/Rituxan (Rituximab) Alone and in Combination With Roferon-A in Patients With Follicular or Other CD20+ Low-Grade (Indolent) Lymphoma
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