Phase II Cancer Vaccine Trial for Patients With Follicular Lymphoma

NCT ID: NCT01926639

Last Updated: 2014-10-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2014-10-31

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.

Conditions

Follicular Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radiotherapy , rituximab and DC

Treatment repeated 3 times and targeting different lymph nodes

Group Type: EXPERIMENTAL

Radiotherapy, rituximab and DC

Intervention Type: BIOLOGICAL

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

Interventions

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

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 -

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Norwegian Cancer Society

OTHER

Sponsor Role: collaborator

Helse Sor-Ost

OTHER_GOV

Sponsor Role: collaborator

Oslo University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Arne Kolstad, MD, PhD

Role: STUDY_CHAIR

Oslo University Hospital

Locations

Oslo University Hospital

Oslo, Oslo County, Norway

Countries

Norway

References

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.

Reference Type: DERIVED

PMID: 25293773 (View on PubMed)

Other Identifiers

2007-002153-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2.2007.1112 Lymvac-1

Identifier Type: -

Identifier Source: org_study_id