A Study of MabThera/Rituxan (Rituximab) Alone and in Combination With Roferon-A in Patients With Follicular or Other CD20+ Low-Grade (Indolent) Lymphoma

August 29, 2014 updated by: Hoffmann-La Roche

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

313

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Hillerod, Denmark, 3400
      • København, Denmark, 2100
      • Roskilde, Denmark, 4000
  • Norway
      • Bergen, Norway, 5021
      • Oslo, Norway, 0407
      • Oslo, Norway, 0379
      • Stavanger, Norway, 4068
      • Tromsø, Norway, 9038
      • Trondheim, Norway, 7000
  • Sweden
      • Eskilstuna, Sweden, 63188
      • Falun, Sweden, 79182
      • Goeteborg, Sweden, 41685
      • Halmstad, Sweden, 30185
      • Huddinge, Sweden, 14186
      • Jonkoping, Sweden, 55185
      • Karlstad, Sweden, 65185
      • Kristianstad, Sweden, 29185
      • Linkoeping, Sweden, 58185
      • Luleå, Sweden, S-971 80
      • Lund, Sweden, 22185
      • Malmoe, Sweden, 21401
      • Stockholm, Sweden, 17176
      • Stockholm, Sweden, 118 83
      • Sundsvall, Sweden, 85186
      • Uddevalla, Sweden, 45180
      • Umea, Sweden, 90185
      • Uppsala, Sweden, 75185
      • Vaxjo, Sweden, 35185
      • Visby, Sweden, 62184
      • Västerås, Sweden, 72189
      • Örebro, Sweden, 701 85

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Rituximab Monotherapy
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.
Drug: rituximab
375 mg/m2 rituximab i.v. weekly for 4 weeks
Other Names:
  • Rituxan
  • MabThera
Experimental: Rituximab, Interferon
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.
Drug: rituximab
375 mg/m2 rituximab i.v. weekly for 4 weeks
Other Names:
  • Rituxan
  • MabThera
Drug: interferon-a-2a
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
Other Names:
  • Roferon-A

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment Failure - Percentage of Participants With an Event
Time Frame: Baseline (BL), Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
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.
Baseline (BL), Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
Treatment Failure - Time to Event
Time Frame: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
The median time, in months, between randomization and treatment failure event determined using Kaplan-Meier estimates.
BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Achieving Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR)
Time Frame: Weeks 10 and 16
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.
Weeks 10 and 16
Percentage of Participants Achieving CR or CRu
Time Frame: Weeks 10 and 16
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.
Weeks 10 and 16
Duration of Response - Percentage of Participants With an Event
Time Frame: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
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.
BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
Duration of Response
Time Frame: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
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.
BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
Disease Progression - Percentage of Participants With an Event
Time Frame: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
A disease progression event was defined as tumor progression or death due to any cause (or a censored observation).
BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
Time to Disease Progression
Time Frame: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
The median time, in months, from randomization to disease progression event assessed using Kaplan-Meier estimates. One month=30.4 days
BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
Overall Survival (OS) - Percentage of Participants With an Event
Time Frame: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
An overall survival event was defined as death due to any cause.
BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
Overall Survival
Time Frame: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period
The median time, in months, from randomization to OS event assessed using Kaplan-Meier estimates. One month=30.4 days
BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Collaborators

Nordic Lymphoma Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2002

Primary Completion (Actual)

July 1, 2011

Study Completion (Actual)

July 1, 2011

Study Registration Dates

First Submitted

May 29, 2012

First Submitted That Met QC Criteria

May 29, 2012

First Posted (Estimate)

May 31, 2012

Study Record Updates

Last Update Posted (Estimate)

September 8, 2014

Last Update Submitted That Met QC Criteria

August 29, 2014

Last Verified

August 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ML16865

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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