Clinical trial NCT00637117: Intratumoral Dendritic Cell Vaccination Combined With Local Radiotherapy in Patients With Recurrent Lymphoma.
Official title: A Phase I/II Study of Intratumoral Dendritic Cell Vaccination Combined With Local Radiotherapy in Patients With Recurrent Lymphoma.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Lymphoma
Keywords: Lymphoma, Dendritic, Vaccine, Radiotherapy
Lead sponsor: Baylor Research Institute
Sponsor class: OTHER
First posted: 2008-03-17
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to gather data on feasibility and on immune and clinical efficacy of intratumoral dendritic cell (DC) vaccination in combination with local radiotherapy in patients with recurrent lymphoma

Detailed description: Lymphoma is extremely sensitive to radiation and is a commonly used therapy. The major issue in application of local radiotherapy is the relative short duration of response and as a consequence is used mainly for palliation. Therefore novel therapies are needed to improve the outcome of patients with lymphomas. The potential specificity of the immune system to recognize and eliminate tumor cells is especially relevant in lymphoma. Immune responses are induced, coordinated and regulated by dendritic cells (DCs), the most potent antigen-presenting cells. Based on the central role of DCs in initiating immune responses, four vaccinations will be administered at intervals beginning two days after low dose radiation is given to the tumor site.

Eligibility criteria: Inclusion Criteria:

* Biopsy confirmed recurrent lymphoma of any initial stage, either Hodgkin's lymphoma or the B cell or T cell NHL of an indolent nature. For B cell lymphoma, follicular lymphoma, small lymphocytic lymphoma, marginal zone lymphoma, and those indolent patients with mantle cell lymphoma or diffuse large B cell lymphoma will be included. For T cell lymphoma, the patients with indolent cutaneous T cell lymphomas (mycosis fungoides or primary cutaneous anaplastic large cell lymphoma) who have failed or have been intolerant of one systemic or two topical treatments will be included.
* Patients must have failed at least one line of prior treatment but not more than four (including autologous but not allogeneic stem cell transplant).
* Patients must have at least one site of disease that is accessible for intratumoral injection of DCs percutaneously after palliative local radiotherapy
* Tumor specimens must be available for immunological studies either from a previous biopsy or a new biopsy obtained before the initiation of the treatment.
* Patients must have measurable disease other than the injection site or biopsy site.
* 18 years of age or older.
* Karnofsky Performance Status (KPS) of \> 70.
* Adequate bone marrow function: WBC \>2000/uL, platelet count \>75,000/mm3; ANC\>1000.
* Adequate hepatic function: bilirubin \<= 1.5 mg/dL; SGOT/SGPT\<2.5x upper limit of normal
* Adequate renal function: serum creatinine \<= 2.0mg/dL.
* Required wash out periods for prior therapy:
* Topical therapy: 2 weeks
* Chemotherapy: 4 weeks (12 weeks for purine analogs)
* Radiotherapy (including photo therapy): 4 weeks
* Other systemic biological therapy: 4 weeks
* Other investigational therapy: 4 weeks
* Patients of reproductive potential and their partners must agree to use an effective (\>90% reliability) form of contraception during the study and for 4 weeks following the last study drug administration.
* Women of reproductive potential must have negative urine pregnancy test.
* Life expectancy greater than 4 months.
* Able to comply with the treatment schedule.

Exclusion Criteria:

* Pre-existing autoimmune or antibody mediated disease including: systemic lupus, erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia, etc, but excluding controlled thyroid disease, or the presence of autoantibodies without clinical autoimmune disease.
* Known history of human immunodeficiency virus (HIV) or hepatitis B or C.
* CNS metastases
* Prior malignancy (active within 5 years of screening) except basal cell or completely excised non-invasive squamous cell carcinoma of the skin, or in situ squamous cell carcinoma of the cervix.
* Current anticoagulant therapy (ASA\<= 325 mg/day allowed).
* Significant cardiovascular disease (i.e., NYHA class 3 congestive heart failure; myocardial infarction with the past 6 months; unstable angina; coronary angioplasty with the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias).
* Pregnant or lactating.
* Prior therapy with allogeneic stem cell transplant.
* Any other medical history, including laboratory results, deemed by the investigator to be likely to interfere with their participation in the study, or to interfere with the interpretation of the results.

Primary outcomes:
measure: Safety and feasibility of intratumoral dendritic cell vaccination
timeFrame: 2 years
Secondary outcomes:
measure: Clinical activity-response in local and distant lesions
timeFrame: 2 years
measure: Immunological response with conventional CTL assay, proliferation assay and microarray-based immune gene profiling using peripheral blood and/or biopsied tumor
timeFrame: 2 years
Other outcomes:
Locations:
Study officials:
name: Karolina Palucka, MD, PhD
role: STUDY_DIRECTOR
References: