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

Sponsor:	North Central Cancer Treatment Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00026182

Purpose

RATIONALE: 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.

PURPOSE: 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's lymphoma.

Condition	Intervention	Phase
Lymphoma	Biological: recombinant interleukin-12 Biological: rituximab	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
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:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Rituximab Interleukin-12

U.S. FDA Resources

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

Study Start Date:	October 2001
Primary Completion Date:	February 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Compare the objective response in patients with B-cell non-Hodgkin's lymphoma treated with rituximab and 2 different schedules of interleukin-12*. (Arm II closed to accrual as of 11/13/03.)
Compare the toxic effects of these regimens in these patients.
Determine the objective response rate in patients with mantle cell lymphoma treated with these regimens.
Determine the overall and progression-free survival of patients treated with these regimens.
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 II closed to accrual as of 11/14/03.)

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

DISEASE CHARACTERISTICS:

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* NOTE: *Closed to accrual as of 3/10/04
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 NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-1

Life expectancy:

At least 12 weeks

Hematopoietic:

Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 75,000/mm^3
Hemoglobin ≥ 8 g/dL

Hepatic:

Bilirubin ≤ 3 times upper limit of normal (ULN)
AST and ALT ≤ 3 times ULN
Alkaline phosphatase ≤ 3 times ULN

Renal:

Creatinine ≤ 2 times ULN

Cardiovascular:

No New York Heart Association class III or IV heart disease
No history of angina

Other:

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 CONCURRENT THERAPY:

Biologic therapy:

Prior stem cell transplantation allowed
More than 12 months since prior rituximab
No prior interleukin-12
No other concurrent immunotherapy

Chemotherapy:

Recovered from prior chemotherapy
No concurrent chemotherapy

Endocrine therapy:

No concurrent steroid therapy

Radiotherapy:

No concurrent radiotherapy

Surgery:

Not specified

Other:

Any number of prior therapies allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00026182

Locations

United States, Arizona
CCOP - Scottsdale Oncology Program
Scottsdale, Arizona, United States, 85259-5404
United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
United States, Illinois
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
CCOP - Illinois Oncology Research Association
Peoria, Illinois, United States, 61602
United States, Iowa
CCOP - Cedar Rapids Oncology Project
Cedar Rapids, Iowa, United States, 52403-1206
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, United States, 50309-1016
Siouxland Hematology-Oncology
Sioux City, Iowa, United States, 51101-1733
United States, Kansas
CCOP - Wichita
Wichita, Kansas, United States, 67214-3882
United States, Michigan
CCOP - Michigan Cancer Research Consortium
Ann Arbor, Michigan, United States, 48106
United States, Minnesota
CCOP - Duluth
Duluth, Minnesota, United States, 55805
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, United States, 55416
CentraCare Health Plaza
Saint Cloud, Minnesota, United States, 56303
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Nebraska
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, United States, 68106
United States, North Dakota
CCOP - Merit Care Hospital
Fargo, North Dakota, United States, 58122
Medcenter One Health System
Bismarck, North Dakota, United States, 58501-5505
United States, Ohio
CCOP - Toledo Community Hospital
Toledo, Ohio, United States, 43623-3456
United States, Pennsylvania
CCOP - Geisinger Clinic and Medical Center
Danville, Pennsylvania, United States, 17822-2001
United States, South Dakota
CCOP - Sioux Community Cancer Consortium
Sioux Falls, South Dakota, United States, 57104
Rapid City Regional Hospital
Rapid City, South Dakota, United States, 57709
United States, Wisconsin
CCOP - St. Vincent Hospital Cancer Center, Green Bay
Green Bay, Wisconsin, United States, 54301
Canada, Saskatchewan
Allan Blair Cancer Centre
Regina, Saskatchewan, Canada, S4T 7T1

Sponsors and Collaborators

North Central Cancer Treatment Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Stephen M. Ansell, MD, PhD

Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Ansell SM, Geyer SM, Maurer MJ, Kurtin PJ, Micallef IN, Stella P, Etzell P, Novak AJ, Erlichman C, Witzig TE. Randomized phase II study of interleukin-12 in combination with rituximab in previously treated non-Hodgkin's lymphoma patients. Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6056-63.

Ansell SM, Geyer SM, Witzig TE, et al.: NCCTG trial of concomitant or sequential IL-12 in combination with rituximab in previously treated non-Hodgkin lymphoma patients. [Abstract] J Clin Oncol 22 (Suppl 14): A-6591, 580s, 2004.

Ansell SM, Grote DM, Witzig TE, et al.: Lack of increased clinical efficacy when interleukin-12 is added to rituximab in B-Cell lymphoma patients is related to inadequate delivery of the cytokine to the sites of lymphoma. [Abstract] Blood 104 (11): A-1397, 2004.

Study ID Numbers:	CDR0000068994, NCCTG-N0087
Study First Received:	November 9, 2001
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00026182 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent mantle cell lymphoma

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immunoproliferative Disorders
Interleukin-12
Immune System Diseases
Immunologic Factors
Antineoplastic Agents
Rituximab
Growth Substances
Physiological Effects of Drugs
Adjuvants, Immunologic
Angiogenesis Inhibitors

Pharmacologic Actions
Lymphoma, B-Cell
Lymphatic Diseases
Neoplasms
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Antirheumatic Agents
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Lymphoma

ClinicalTrials.gov processed this record on November 27, 2009