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

• ClinicalTrials.gov Identifier: NCT01609010
• Recruitment Status: Completed
• First Posted: May 31, 2012
• Results First Posted: June 25, 2014
• Last Update Posted: September 8, 2014
• Sponsor: Hoffmann-La Roche
• Collaborator: Nordic Lymphoma Group
• Information provided by (Responsible Party): Hoffmann-La Roche

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.

Condition or disease	Intervention/treatment	Phase
Lymphoma	Drug: rituximab; Drug: interferon-a-2a	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 313 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: October 2002
• Actual Primary Completion Date: July 2011
• Actual Study Completion Date: July 2011

Arms and Interventions

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: MabThera; Rituxan
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: MabThera; Rituxan; 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 Name: Roferon-A

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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).
6. 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
7. 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.
8. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Denmark

Hillerod, Denmark, 3400

København, Denmark, 2100

Roskilde, Denmark, 4000

Norway

Bergen, Norway, 5021

Oslo, Norway, 0379

Oslo, Norway, 0407

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, 118 83

Stockholm, Sweden, 17176

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

Sponsors and Collaborators

Hoffmann-La Roche

Nordic Lymphoma Group

Investigators

• Study Chair: Clinical Trials; Hoffmann-La Roche

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kimby E, Östenstad B, Brown P, Hagberg H, Erlanson M, Holte H, Linden O, Johansson AS, Ahlgren T, Wader K, Wahlin BE, Delabie J, Sundström C; Nordic Lymphoma Group (NLG). Two courses of four weekly infusions of rituximab with or without interferon-α2a: 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.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01609010
• Other Study ID Numbers: ML16865
• First Posted: May 31, 2012
• Results First Posted: June 25, 2014
• Last Update Posted: September 8, 2014
• Last Verified: August 2014

Additional relevant MeSH terms:

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Interferons; Interferon alpha-2; Rituximab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antiviral Agents; Anti-Infective Agents