Lymvac-1: Phase II Cancer Vaccine Trial for Patients With Follicular Lymphoma

Sponsor

Oslo University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01926639

Collaborator

Norwegian Cancer Society (Other), Helse Sor-Ost (Other)

Enrollment

Location

Arm

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Patients with non-curable disseminated follicular lymphoma receive local radiotherapy targeting single lymph nodes and injection of low-dose rituximab (anti-CD20) and autologous dendritic cells. The therapy is repeated 3 times, targeting different lesion. Aims are to induce tumor immunity and clinical responses.

Condition or Disease	Intervention/Treatment	Phase
Follicular Lymphoma	Biological: Radiotherapy, rituximab and DC	Phase 2

Detailed Description

The clinical protocol is based on the rationale that the immune system has been developed to combat infectious disease. To mimic the environment in infected tissue, selected tumor-affected lymph nodes are treated locally with a single dose of 8 Gy radiotherapy and injected with therapeutic antibody (anti-CD20/Rituximab). Later, dendritic cells (DC) are injected into the damaged tumor tissue together with a stimulatory cytokine (GM-CSF) to initiate an immune response. Patients with untreated or relapsed stage III/IV follicular lymphoma not in need of standard therapy receive intra-tumoral injections of low-dose anti-CD20 antibodies (5 mg) on days 1 and 3 and local radiotherapy on day 2. On days 4 and 5, dendritic cells generated from monocytes isolated from the patients blood are injected into the site together with the stimulatory cytokine GM-CSF administered subcutaneously. Additional lymph nodes are treated similarly after 2 and 4 weeks. The treatment is thus performed three times, targeting different lymphoma nodes. The primary aims are to induce tumor-specific immune responses and clinical responses.

Study Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Radiotherapy Combined With Intratumoral Injections of Dendritic Cells and Rituximab - a Phase II Cancer Vaccine Trial for Patients With Untreated and Relapsed Indolent Non-Hodgkin's Lymphoma

Study Start Date :

Oct 1, 2009

Actual Primary Completion Date :

Oct 1, 2014

Actual Study Completion Date :

Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Radiotherapy , rituximab and DC Treatment repeated 3 times and targeting different lymph nodes	Biological: Radiotherapy, rituximab and DC Lymphoma lymph nodes are irradiated with 8 Gy single treatment and injected with rituximab (5 mg) and autologous DC intratumorally. The treatment is performed 3 times targeting different lymph nodes

Arm

Intervention/Treatment

Experimental: Radiotherapy , rituximab and DC

Treatment repeated 3 times and targeting different lymph nodes

Biological: Radiotherapy, rituximab and DC

Lymphoma lymph nodes are irradiated with 8 Gy single treatment and injected with rituximab (5 mg) and autologous DC intratumorally. The treatment is performed 3 times targeting different lymph nodes

Outcome Measures

Primary Outcome Measures

Response rate [5 years]
Clinical response measured by CT and PET/CT and immune response

Secondary Outcome Measures

Immune response [1 year]
Immune response measured by flow cytometry. Peripheral blood mononuclear cells before and after treatment are cultures along with autologous tumor cells. Proliferation is measured.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18 years and older
Histologically confirmed (by WHO classification) untreated and relapsed indolent non-Hodgkin's B-cell lymphoma of low-grade follicular, marginal zone, lymphoplasmocytic or small lymphocytic subtypes.
Stage III/IV
Adequate bone marrow function (leukocyte count>2,0, neutrophil count>1.0, platelets>50)
Two or more separate lymph nodes > 1,5 cm available for biopsy or treatment.
Measurable disease present other than biopsy site and injection site(s).
Required wash-out period after previous treatment: Chemotherapy - 8 weeks, Radiotherapy - 4 weeks, Rituximab - 12 weeks
WHO status 0-1
Life expectancy of more than 6 months
Written informed consent
Able to comply with the treatment protocol -

Exclusion Criteria:

Patients with progressive lymphoma in need of systemic therapy or standard dose irradiation.
Chronic bacterial, viral or fungal infection
Pre-existing autoimmune or antibody mediated disease including: systemic lupus, erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia, but excluding controlled thyroid disease, or the presence of autoantibodies without clinical autoimmune disease.
Known history of HIV
Central nervous system involvement of lymphoma
Current anticoagulant therapy which can not safely be paused during treatment injections (ASA < 325 mg/day allowed)
Pregnancy -