Phase II Cancer Vaccine Trial for Patients With Follicular Lymphoma (Lymvac-1)
Primary Purpose
Follicular Lymphoma
Status
Completed
Phase
Phase 2
Locations
Norway
Study Type
Interventional
Intervention
Radiotherapy, rituximab and DC
Sponsored by
About this trial
This is an interventional treatment trial for Follicular Lymphoma focused on measuring Follicular lymphoma, Rituximab, Autologous dendritic cells, Cancer vaccine
Eligibility Criteria
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 -
Sites / Locations
- Oslo University Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Radiotherapy , rituximab and DC
Arm Description
Treatment repeated 3 times and targeting different lymph nodes
Outcomes
Primary Outcome Measures
Response rate
Clinical response measured by CT and PET/CT and immune response
Secondary Outcome Measures
Immune response
Immune response measured by flow cytometry. Peripheral blood mononuclear cells before and after treatment are cultures along with autologous tumor cells. Proliferation is measured.
Full Information
NCT ID
NCT01926639
First Posted
August 19, 2013
Last Updated
October 22, 2014
Sponsor
Oslo University Hospital
Collaborators
Norwegian Cancer Society, Helse Sor-Ost
1. Study Identification
Unique Protocol Identification Number
NCT01926639
Brief Title
Phase II Cancer Vaccine Trial for Patients With Follicular Lymphoma
Acronym
Lymvac-1
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 Type
Interventional
2. Study Status
Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
October 2009 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
October 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Oslo University Hospital
Collaborators
Norwegian Cancer Society, Helse Sor-Ost
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Follicular Lymphoma
Keywords
Follicular lymphoma, Rituximab, Autologous dendritic cells, Cancer vaccine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Radiotherapy , rituximab and DC
Arm Type
Experimental
Arm Description
Treatment repeated 3 times and targeting different lymph nodes
Intervention Type
Biological
Intervention Name(s)
Radiotherapy, rituximab and DC
Intervention Description
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
Primary Outcome Measure Information:
Title
Response rate
Description
Clinical response measured by CT and PET/CT and immune response
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Immune response
Description
Immune response measured by flow cytometry. Peripheral blood mononuclear cells before and after treatment are cultures along with autologous tumor cells. Proliferation is measured.
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 -
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arne Kolstad, MD, PhD
Organizational Affiliation
Oslo University Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Oslo University Hospital
City
Oslo
ZIP/Postal Code
0310
Country
Norway
12. IPD Sharing Statement
Citations:
PubMed Identifier
25293773
Citation
Kolstad A, Kumari S, Walczak M, Madsbu U, Hagtvedt T, Bogsrud TV, Kvalheim G, Holte H, Aurlien E, Delabie J, Tierens A, Olweus J. Sequential intranodal immunotherapy induces antitumor immunity and correlated regression of disseminated follicular lymphoma. Blood. 2015 Jan 1;125(1):82-9. doi: 10.1182/blood-2014-07-592162. Epub 2014 Oct 7.
Results Reference
derived
Learn more about this trial
Phase II Cancer Vaccine Trial for Patients With Follicular Lymphoma
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