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

Phase 3

Completed

• Conditions: Lymphoma
• Interventions: Drug: rituximab; Drug: interferon-a-2a

• Registration Number: NCT01609010
• Lead Sponsor: Hoffmann-La Roche

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2002-10
• Primary Completion: 2011-07
• Study Completion: 2011-07
• Study First Submitted: 2012-05-29
• Study First Submitted QC: 2012-05-29
• Study First Posted: 2012-05-31
• Results First Submitted: 2014-05-23
• Results First Submitted QC: 2014-05-23
• Results First Posted: 2014-06-25
• Status Verified: 2014-08
• Last Update Submitted: 2014-08-29
• Last Update Posted: 2014-09-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 313

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Rituximab, Interferon	interferon-a-2a	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.
Rituximab Monotherapy	rituximab	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.
Rituximab, Interferon	rituximab	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.

Primary Outcome Measures

Name	Time	Method
Treatment Failure - Time to Event	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.
Treatment Failure - Percentage of Participants With an Event	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR)	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.
Overall Survival (OS) - Percentage of Participants With an Event	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.
Percentage of Participants Achieving CR or CRu	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.
Time to Disease Progression	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
Duration of Response - Percentage of Participants With an Event	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.
Disease Progression - Percentage of Participants With an Event	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).
Overall Survival	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
Duration of Response	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.