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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01609010
• Other study ID #: ML16865
• Status: Completed
• Phase: Phase 3
• First received: May 29, 2012
• Last updated: August 29, 2014
• Start date: October 2002
• Est. completion date: July 2011

Study information

• Verified date: August 2014
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Medical Products Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 313
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma

Intervention

Drug:
• rituximab
375 mg/m2 rituximab i.v. weekly for 4 weeks
• 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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Nordic Lymphoma Group

Countries where clinical trial is conducted

Denmark,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline (BL), Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period	No
Primary	Treatment Failure - Time to Event	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	No
Secondary	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.	Weeks 10 and 16	No
Secondary	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.	Weeks 10 and 16	No
Secondary	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.	BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period	No
Secondary	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.	BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period	No
Secondary	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).	BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period	No
Secondary	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	BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period	No
Secondary	Overall Survival (OS) - Percentage of Participants With an Event	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	No
Secondary	Overall Survival	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	No