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

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

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.

Study Overview

• Status: Completed
• Conditions: Follicular Lymphoma
• Intervention / Treatment: Biological: Radiotherapy, rituximab and DC

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 Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0310
    • Oslo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 years and older
2. 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.
3. Stage III/IV
4. Adequate bone marrow function (leukocyte count>2,0, neutrophil count>1.0, platelets>50)
5. Two or more separate lymph nodes > 1,5 cm available for biopsy or treatment.
6. Measurable disease present other than biopsy site and injection site(s).
7. Required wash-out period after previous treatment: Chemotherapy - 8 weeks, Radiotherapy - 4 weeks, Rituximab - 12 weeks
8. WHO status 0-1
9. Life expectancy of more than 6 months
10. Written informed consent
11. Able to comply with the treatment protocol -

Exclusion Criteria:

1. Patients with progressive lymphoma in need of systemic therapy or standard dose irradiation.
2. Chronic bacterial, viral or fungal infection
3. 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.
4. Known history of HIV
5. Central nervous system involvement of lymphoma
6. Current anticoagulant therapy which can not safely be paused during treatment injections (ASA < 325 mg/day allowed)
7. Pregnancy -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	Clinical response measured by CT and PET/CT and immune response	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1 year

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: Norwegian Cancer Society; Helse Sor-Ost
• Investigators: Study Chair: Arne Kolstad, MD, PhD, Oslo University Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: August 19, 2013
• First Submitted That Met QC Criteria: August 19, 2013
• First Posted (Estimate): August 21, 2013

Study Record Updates

• Last Update Posted (Estimate): October 23, 2014
• Last Update Submitted That Met QC Criteria: October 22, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Rituximab; Follicular lymphoma; Autologous dendritic cells; Cancer vaccine
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Follicular; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: 2.2007.1112 Lymvac-1; 2007-002153-23 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No