Biological Therapy Plus Monoclonal Antibody Therapy in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

Sponsor

Jonsson Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00040950

Collaborator

National Cancer Institute (NCI) (NIH)

Location

Duration (Months)

Study Details

Study Description

Brief Summary

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. Biological therapies such as CpG 7909 use different ways to stimulate the immune system and stop cancer cells from growing. Combining CpG 7909 with rituximab may kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of CpG 7909 plus rituximab in treating patients who have relapsed or refractory non-Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: rituximab Drug: agatolimod sodium	Phase 1

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose of subcutaneous and IV CpG 7909 when administered with rituximab in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.
Determine the safety and tolerability of this regimen in these patients.
Determine the disease response in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of CpG 7909. Patients are sequentially assigned to 1 of 2 treatment groups.

Group A: Patients receive rituximab IV over 4-5 hours followed by CpG 7909 IV over 2 hours on day 1. Courses repeat weekly for 4 weeks.
Group B: Patients receive rituximab as above followed by CpG 7909 subcutaneously on day

Courses repeat weekly for 4 weeks.

Cohorts of 3-6 patients receive escalating doses of CpG 7909 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 4 weeks.

PROJECTED ACCRUAL: A total of 6-48 patients (3-24 per treatment group) will be accrued for this study.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

A Multi-Center, Phase I, Open Label, Two Arm, Non-Randomized, Dose-Escalation, Study Of The Safety And Tolerability Of CPG 7909 In Patients Receiving Rituxan For Relapsed Or Refractory B-Cell Non-Hodgkin's Lymphoma

Study Start Date :

Mar 1, 2002

Actual Study Completion Date :

Oct 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed CD20+ B-cell non-Hodgkin's lymphoma (NHL)
CD20 positive by immunohistochemistry or flow cytometry
Relapsed or refractory disease
Bidimensionally measurable disease
Sole site of measurable disease within a previously irradiated field allowed provided there was disease progression at that site
No pre-existing ascites or pleural effusions
No known CNS involvement by NHL

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-2

Life expectancy:

More than 3 months

Hematopoietic:

Neutrophil count at least 1,000/mm3
Platelet count at least 50,000/mm3

Hepatic:

Bilirubin less than 2 mg/dL
Transaminase less than 2 times upper limit of normal
No hepatitis B or C

Renal:

Creatinine less than 2 mg/dL

Cardiovascular:

No significant cardiovascular disease
No New York Heart Association class III congestive heart failure
No myocardial infarction within the past 6 months
No unstable angina
No uncontrolled atrial or ventricular cardiac arrhythmias

Pulmonary:

No concurrent significant pulmonary disease

Other:

HIV negative
No acute infection requiring antibiotics
No fever over 38.2 degrees C within the past 3 days
No other malignancy within the past 5 years except basal cell or noninvasive squamous cell skin cancer or carcinoma in situ of the cervix
No pre-existing autoimmune disease or antibody-mediated disease, including:
Systemic lupus erythematosus
Rheumatoid arthritis
Multiple sclerosis
Sjogren's syndrome
Autoimmune thrombocytopenia
Controlled thyroid disease allowed
Concurrent autoantibodies without clinical autoimmune disease allowed
No history of allergic reactions attributed to compounds of similar composition to study drugs
No other medical history, including laboratory results, that would preclude study
No suspected or confirmed poor compliance or mental instability that would preclude study
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No prior allogeneic transplantation
More than 30 days since prior hematopoietic growth factors (e.g., filgrastim (G-CSF) or epoetin alfa)
More than 30 days since prior immunotherapy
More than 90 days since prior monoclonal antibodies as monotherapy for patients who were unresponsive to treatment (30 days for patients who responded to treatment and subsequently relapsed)
No other concurrent biological agents
No concurrent hematopoietic growth factors (e.g., G-CSF or epoetin alfa)