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

Hoffmann-La Roche313 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

313

Conditions

Lymphoma

Interventions

rituximab

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (31)

Unnamed facility

Copenhagen, Denmark

Unnamed facility

Hillerød, Denmark

Unnamed facility

Roskilde, Denmark

Unnamed facility

Bergen, Norway

Unnamed facility

Oslo, Norway

Unnamed facility

Oslo, Norway

Unnamed facility

Stavanger, Norway

Unnamed facility

Tromsø, Norway

Unnamed facility

Trondheim, Norway

Unnamed facility

Eskilstuna, Sweden

...and 21 more locations

Outcomes

Primary Outcomes

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.

Time frame: 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

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 Outcomes

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.

Time frame: Weeks 10 and 16

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.

Time frame: Weeks 10 and 16

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.

Time frame: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period

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.

Time frame: 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

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

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

Time frame: 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

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

Overall Survival

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