Rituximab and Interleukin-12 in Treating Patients With B-Cell Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00026182
First received: November 9, 2001
Last updated: August 23, 2013
Last verified: August 2013
  Purpose

Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Interleukin-12 may kill cancer cells by stopping blood flow to the tumor and by stimulating a person's white blood cells to kill cancer cells. Combining rituximab with interleukin-12 may kill more cancer cells. This randomized phase II trial is comparing how well giving rituximab together with two different schedules of interleukin-12 works in treating patients with B-cell non-Hodgkin lymphoma.


Condition Intervention Phase
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Nodal Marginal Zone B-cell Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Small Lymphocytic Lymphoma
Splenic Marginal Zone Lymphoma
Biological: rituximab
Biological: recombinant interleukin-12
Other: laboratory biomarker analysis
Other: questionnaire administration
Procedure: quality-of-life assessment
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Study Of Interleukin-12 In Combination With Rituximab In Patients With Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective response [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. In addition, confidence intervals for the response probability will be calculated according to the approach of Duffy and Santner.

  • Objective response [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. In addition, confidence intervals for the response probability will be calculated according to the approach of Duffy and Santner.


Secondary Outcome Measures:
  • Overall response rate for MCL patients [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Corresponding 95% confidence intervals will also be calculated.

  • Overall survival [ Time Frame: From randomization to death due to any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    The distribution this time measure will be estimated using the method of Kaplan-Meier.

  • Time to treatment failure [ Time Frame: From randomization to the treatment-specific definition of disease progression, death, or when the patient goes off study due to refusal or toxicity, assessed up to 5 years ] [ Designated as safety issue: No ]
    The distribution this time measure will be estimated using the method of Kaplan-Meier.

  • Complete response rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Will be assessed and descriptively summarized.

  • Quality of life assessed using FACT-BRM [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Before and after treatment comparisons will be made using a paired samples t-test or its nonparametric equivalent. This two-sided test will have at least 80% power to detect a moderate effect size (0.42 times the standard deviation) in the FACT-BRM scores.

  • Quality of life assessed using FACT-BRM [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Before and after treatment comparisons will be made using a paired samples t-test or its nonparametric equivalent. This two-sided test will have at least 80% power to detect a moderate effect size (0.42 times the standard deviation) in the FACT-BRM scores.

  • Quality of life assessed using FACT-BRM [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Before and after treatment comparisons will be made using a paired samples t-test or its nonparametric equivalent. This two-sided test will have at least 80% power to detect a moderate effect size (0.42 times the standard deviation) in the FACT-BRM scores.


Enrollment: 99
Study Start Date: October 2001
Primary Completion Date: February 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (rituximab and recombinant interleukin-12)
Patients receive rituximab IV on days 1, 8, 15, and 22. Patients receive interleukin-12 SC twice weekly beginning on day 2 and continuing until disease progression.
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Biological: recombinant interleukin-12
Given SC
Other Names:
  • cytotoxic lymphocyte maturation factor
  • IL-12
  • interleukin-12
  • natural killer cell stimulatory factor
  • Ro 24-7472
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Arm II (rituximab and recombinant interleukin-12)
Patients receive rituximab as in arm I. Patients are evaluated at week 12. Patients with stable or progressive disease receive interleukin-12 SC twice weekly until disease progression or for 24 weeks. Patients with a complete or partial response after rituximab are monitored until disease progression and then begin interleukin-12 SC twice weekly until further disease progression.
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Biological: recombinant interleukin-12
Given SC
Other Names:
  • cytotoxic lymphocyte maturation factor
  • IL-12
  • interleukin-12
  • natural killer cell stimulatory factor
  • Ro 24-7472
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

Detailed Description:

OBJECTIVES:

I. Compare the objective response in patients with B-cell non-Hodgkin's lymphoma treated with rituximab and 2 different schedules of interleukin-12*.

II. Compare the toxic effects of these regimens in these patients. III. Determine the objective response rate in patients with mantle cell lymphoma treated with these regimens.

IV. Determine the overall and progression-free survival of patients treated with these regimens.

V, Compare the quality of life of patients treated with these regimens. NOTE: *Interleukin-12 will no longer be available after 6/30/05.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to histology (mantle cell lymphoma vs other [closed to accrual as of 3/10/04]) and International Prognostic Factor Index (low and low-intermediate risk [closed to accrual as of 3/10/04] vs high-intermediate and high risk). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive rituximab IV on days 1, 8, 15, and 22. Patients receive interleukin-12* subcutaneously (SC) twice weekly beginning on day 2 and continuing until disease progression.

ARM II (closed to accrual as of 11/14/03): Patients receive rituximab as in arm I. Patients are evaluated at week 12. Patients with stable or progressive disease receive interleukin-12* SC twice weekly until disease progression or for 24 weeks. Patients with a complete or partial response after rituximab are monitored until disease progression and then begin interleukin-12 SC twice weekly until further disease progression.

NOTE: *Interleukin-12 will no longer be available after 06/30/05. Patients proceed to follow-up as outlined below.

Quality of life is assessed at baseline and at 3 and 6 months.

Patients are followed every 3 months for 1 year and then every 6 months for up to 4 years.

PROJECTED ACCRUAL: A total of 90 patients (45 per treatment arm [arm II closed to accrual as of 11/14/03]) will be accrued for this study within 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed CD20-positive B-cell non-Hodgkin's lymphoma
  • Previously treated low-grade lymphoma considered incurable with standard therapy

    • Grade I or II follicular lymphoma*
    • Lymphoplasmacytic lymphoma*
    • Small lymphocytic lymphoma*
    • Nodal marginal zone lymphoma*
    • Extranodal marginal zone lymphoma of MALT type*
    • Splenic marginal zone lymphoma*
  • Previously treated mantle cell lymphoma allowed
  • Meets one of the following criteria for measurable disease:

    • Bidimensional diameter at least 1.5 cm by 1.5 cm on physical exam
    • At least 2 cm in one dimension by CT scan, MRI, or plain radiograph imaging
    • Palpable spleen at least 5 cm below the left costal margin
  • No CNS involvement by lymphoma
  • Performance status - ECOG 0-1
  • At least 12 weeks
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 75,000/mm^3
  • Hemoglobin ≥ 8 g/dL
  • Bilirubin ≤ 3 times upper limit of normal (ULN)
  • AST and ALT ≤ 3 times ULN
  • Alkaline phosphatase ≤ 3 times ULN
  • Creatinine ≤ 2 times ULN
  • No New York Heart Association class III or IV heart disease
  • No history of angina
  • No uncontrolled peptic ulcer disease
  • No uncontrolled infection
  • No other active malignancy
  • No autoimmune-related phenomena (e.g., antinuclear antibody less than 2 times ULN, rheumatoid factor less than 2 times ULN, and negative direct Coombs)
  • HIV negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Prior stem cell transplantation allowed
  • More than 12 months since prior rituximab
  • No prior interleukin-12
  • No other concurrent immunotherapy
  • Recovered from prior chemotherapy
  • No concurrent chemotherapy
  • No concurrent steroid therapy
  • No concurrent radiotherapy
  • Any number of prior therapies allowed
  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: NCT00026182

Locations
United States, Minnesota
North Central Cancer Treatment Group
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Stephen Ansell North Central Cancer Treatment Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00026182     History of Changes
Other Study ID Numbers: NCI-2012-01865, NCI-2012-01865, NCCTG-N0087, CDR0000068994, N0087, N0087, U10CA025224
Study First Received: November 9, 2001
Last Updated: August 23, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Mantle-Cell
Leukemia, B-Cell
Leukemia, Lymphoid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Interleukin-12
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Adjuvants, Immunologic
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 20, 2014