Clinical trial NCT00040950: Biological Therapy Plus Monoclonal Antibody Therapy in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma
Keywords: recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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 1. 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.

Eligibility criteria: 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)

Chemotherapy:

* More than 30 days since prior chemotherapy
* No concurrent chemotherapy

Endocrine therapy:

* More than 30 days since prior systemic corticosteroids
* No concurrent systemic corticosteroids

Radiotherapy:

* See Disease Characteristics
* More than 30 days since prior radiotherapy
* No concurrent radiotherapy

Surgery:

* Not specified

Other:

* Recovered from prior therapy
* At least 6 months since prior coronary angioplasty
* More than 30 days since prior immunosuppressants
* More than 30 days since prior participation in an investigational drug study
* No concurrent immunosuppressants
* No concurrent anticoagulants except aspirin at doses no greater than 325 mg/day
* No other concurrent anticancer therapy
* No other concurrent investigational agents

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
Study officials:
affiliation: Jonsson Comprehensive Cancer Center
name: Christos E. Emmanouilides, MD
role: STUDY_CHAIR
References:
citation: Leonard JP, Link BK, Emmanouilides C, Gregory SA, Weisdorf D, Andrey J, Hainsworth J, Sparano JA, Tsai DE, Horning S, Krieg AM, Weiner GJ. Phase I trial of toll-like receptor 9 agonist PF-3512676 with and following rituximab in patients with recurrent indolent and aggressive non Hodgkin's lymphoma. Clin Cancer Res. 2007 Oct 15;13(20):6168-74. doi: 10.1158/1078-0432.CCR-07-0815.