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

This study has been completed.
Sponsor:
Collaborator:
Nordic Lymphoma Group
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01609010
First received: May 29, 2012
Last updated: May 23, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Lymphoma
Drug: rituximab
Drug: interferon-a-2a
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    The median time, in months, between randomization and treatment failure event determined using Kaplan-Meier estimates.


Secondary Outcome Measures:
  • Percentage of Participants Achieving Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR) [ Time Frame: Weeks 10 and 16 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Achieving CR or CRu [ Time Frame: Weeks 10 and 16 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Duration of Response [ Time Frame: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    A disease progression event was defined as tumor progression or death due to any cause (or a censored observation).

  • 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 ] [ Designated as safety issue: No ]
    The median time, in months, from randomization to disease progression event assessed using Kaplan-Meier estimates. One month=30.4 days

  • 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 ] [ Designated as safety issue: No ]
    An overall survival event was defined as death due to any cause.

  • Overall Survival [ Time Frame: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period ] [ Designated as safety issue: No ]
    The median time, in months, from randomization to OS event assessed using Kaplan-Meier estimates. One month=30.4 days


Enrollment: 313
Study Start Date: October 2002
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01609010

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
Sponsors and Collaborators
Hoffmann-La Roche
Nordic Lymphoma Group
Investigators
Study Chair: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01609010     History of Changes
Other Study ID Numbers: ML16865
Study First Received: May 29, 2012
Results First Received: May 23, 2014
Last Updated: May 23, 2014
Health Authority: Sweden: Medical Products Agency

Additional relevant MeSH terms:
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Interferon-alpha
Interferons
Rituximab
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 28, 2014