Dendritic Cell Vaccination for Patients with Solid Tumors

NCT ID: NCT01291420

Last Updated: 2024-12-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-03
• Study Completion Date: 2017-11-02

Brief Summary

The aim of this study is to evaluate the immunogenicity and clinical efficacy of intradermal vaccination with autologous RNA-modified dendritic cells (DCs) - engineered to express the WT1 protein - in patients with limited spread metastatic solid tumors, i.e. breast cancers, glioblastoma grade IV, sarcomas, malignant mesothelioma and colorectal tumors. Based on the results of our previously performed phase I study with autologous WT1 mRNA-transfected DC, the investigators hypothesize that the vaccination with DC will be well-tolerated and will result in an increase in WT1-specific CD8+ T cell responses.

Conditions

Glioblastoma; Renal Cell Carcinoma; Sarcomas; Breast Cancers; Malignant Mesothelioma; Colorectal Tumors

Study Design

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

Interventions

autologous dendritic cell vaccination

4 biweekly intradermal DC injections of 10\*10E6 DCs (500 µL) at 5 sites (100 µL/site) in the ventromedial regions of the upper arm approximately 5-10 cm of the regional lymph nodes

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Tumor type:

Metastatic or Locally Advanced Breast Cancer; Malignant Mesothelioma; Glioblastoma Multiforme (Grade IV); Sarcoma's; Colorectal tumors or rare tumors (less than 500 patients a year)

2. Extent of disease:

• Metastatic Breast Cancer or High Risk Locally Advanced Breast Cancer

• Partial or Complete response after first line chemotherapy for both metastatic or locally advanced breast cancer. Minimal metastatic disease under hormonal treatment
• High risk Locally Advanced breast cancer defined as (and/or):

• Age < 60 years old
• ER, PR and Her-2 Neu negative tumors
• > 4 lymphnodes at initial presentation
• Mastitis Carcinomatosis
• Pregnancy associated Breast Cancer
• Malignant Mesothelioma:

• Partial or Complete response after first line chemotherapy not amendable for surgery
• Adjuvant after debulking surgery
• Glioblastoma Multiforme

• In Recurrent Disease after optimal treatment according to Stupp regimen
• In primary disease after debulking surgery, Temodal/radiotherapy and Temodal chemotherapy for 6 months
• Sarcoma's

• After adjuvant chemotherapy for uterine sarcoma's
• After Optimal or Debulking Surgery for liposarcoma's, synovial cell sarcoma's
• Recurrent sarcoma's with limited disease
• Colorectal tumors

• K-ras wild-type tumors with inoperable lymphnode metastasis after standard chemotherapy (FOLFOX, FOLFIRI)

3. Patient Characteristics

• Prior treatments: Patients must have received at least one prior chemotherapeutic regimen and must be more than 1 month past the last treatment.
• Age: ≥ 18 years old
• Performance status: WHO PS grade 0-1 (Appendix B)
• Objectively assessable parameters of life expectancy: more than 3 months
• Prior and concomitant associated diseases allowed with the exception of underlying autoimmune disease and positive serology for HIV/HBV/HCV
• No concomitant use of immunosuppressive drugs, hormonal treatment for breast cancer is allowed in case of stable disease
• Adequate renal and liver function, i.e. creatinin and bilirubin = 1.2 times the upper limit of normal
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
• Women of child-bearing potential should use adequate contraception prior to study entry and for the duration of study participation

Exclusion Criteria

1. Subjects with concurrent additional malignancy (with exception of non-melanoma skin cancers and carcinoma in situ of the cervix)

2. Subjects who are pregnant

3. Subjects who have sensitivity to drugs that provide local anesthesia

4. Subjects needing corticosteroids 1 mg/kg during vaccination; corticosteroids are allowed as part of their treatment when taken ≥ 30 days before the start of vaccination.

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

Sponsors

University Hospital, Antwerp

OTHER

Sponsor Role: lead

Responsible Party

Zwi Berneman

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Antwerp University Hospital, Center for Cellular Therapy and Regenerative Medicine

Edegem, Antwerp, Belgium

Countries

Belgium

References

Van Tendeloo VF, Van de Velde A, Van Driessche A, Cools N, Anguille S, Ladell K, Gostick E, Vermeulen K, Pieters K, Nijs G, Stein B, Smits EL, Schroyens WA, Gadisseur AP, Vrelust I, Jorens PG, Goossens H, de Vries IJ, Price DA, Oji Y, Oka Y, Sugiyama H, Berneman ZN. Induction of complete and molecular remissions in acute myeloid leukemia by Wilms' tumor 1 antigen-targeted dendritic cell vaccination. Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13824-9. doi: 10.1073/pnas.1008051107. Epub 2010 Jul 14.

Reference Type: BACKGROUND

PMID: 20631300 (View on PubMed)

Smits EL, Anguille S, Cools N, Berneman ZN, Van Tendeloo VF. Dendritic cell-based cancer gene therapy. Hum Gene Ther. 2009 Oct;20(10):1106-18. doi: 10.1089/hum.2009.145.

Reference Type: BACKGROUND

PMID: 19656053 (View on PubMed)

Van Driessche A, Van de Velde AL, Nijs G, Braeckman T, Stein B, De Vries JM, Berneman ZN, Van Tendeloo VF. Clinical-grade manufacturing of autologous mature mRNA-electroporated dendritic cells and safety testing in acute myeloid leukemia patients in a phase I dose-escalation clinical trial. Cytotherapy. 2009;11(5):653-68. doi: 10.1080/14653240902960411.

Reference Type: BACKGROUND

PMID: 19530029 (View on PubMed)

Other Identifiers

CCRG 11-001

Identifier Type: -

Identifier Source: org_study_id