Phase I/IIa AdCD40L Immunogene Therapy for Malignant Melanoma
This study is currently recruiting participants.
Verified June 2011 by Uppsala University
Sponsor:
Uppsala University
Collaborator:
Uppsala University Hospital
Information provided by (Responsible Party):
Uppsala University
ClinicalTrials.gov Identifier:
NCT01455259
First received: October 11, 2011
Last updated: October 17, 2011
Last verified: June 2011
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Purpose
In this phase I/II trial, immunostimulatory gene therapy (AdCD40L) will be investigated +/- low dose cyclophosphamide in patients with disseminated malignant melanoma. AdCD40L is an adenoviral nonreplicating vector carrying the human CD40L gene. AdCD40L infects tumor cells upon intratumoral injection and deliver the CD40L gene into the cells whereupon the virus is destroyed. CD40L is then expressed as a membrane-bound protein and interacts with the CD40 receptor expressed by for example dendritic cells (DCs) in the tumor area. DCs mature upon CD40/CD40L interactions and activates tumor-specific T cell responses. AdCD40L (weekly injections of 2.5x10e11 VP, 4x; total dose 1x10e12 VP) will be used as a single treatment in the 6 first patients. If 2-6 responds, 18 additional patients will be treated. If less than 2 patients responds, the next 9 patients will receive preconditioning with low dose cyclophosphamide (300mg/m2) prior to the first and last AdCD40L injection. If at least 1 of 9 responds, 15 additional patients will be treated. A maximum of 30 patients will be included in this trial.
| Condition | Intervention | Phase |
|---|---|---|
|
Disseminated Malignant Melanoma |
Biological: AdCD40L |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase I/IIa AdCD40L Immunogene Therapy for Malignant Melanoma Patients With Disseminated Disease. |
Resource links provided by NLM:
Further study details as provided by Uppsala University:
Primary Outcome Measures:
- All cause adverse events [ Time Frame: during 10 weeks ] [ Designated as safety issue: Yes ]Adverse events will be documented such as inflammation, fever, pain, changes in blood pressure, pulse etc.
- Immune reactions to adenovirus and spreading of vector [ Time Frame: during 10 weeks ] [ Designated as safety issue: Yes ]Immune reactions to adenovirus will be measured by evaluating the increase of anti-adenoviral antibodies in the patients at different time points. Spreading of vector will be evaluated by real time PCR to detect adenovirus vector in blood (plasma and erytrocyte fraction).
Secondary Outcome Measures:
- Tumor burden as measured by PET/CT and whole body MR [ Time Frame: At enrollment, week 5 and week 9 ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 30 |
| Study Start Date: | September 2011 |
| Estimated Study Completion Date: | December 2013 |
| Estimated Primary Completion Date: | October 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: AdCD40L
Treatments once a week with 2.5x10e11 VP AdCD40L, maximum 4 treatments (total dose 1x10e12 VP). If no effect in less than 2 out of 6 patients, the following patients will receive preconditioning therapy 1-2 days prior to first and last treatment with 300mg/m2 cyclophosphamid.
|
Biological: AdCD40L
Adenoviral serotype 5 vector, E1/E3 deleted. Human CD40L gene insert driven by RSV promoter. Vector diluted in infusion solution, 500uL solution containing 2.5x10e11 VP is intratumorally injected/treatment.
|
Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Histologically proven diagnosis of malignant melanoma, ECOG 0-2.
- Disease progression on established treatments.
- Disseminated disease with at least 2 measurable tumor lesions.
- Signed informed consent must be obtained.
Exclusion Criteria:
- Pregnancy.
- Other malignancy within 5 years of study.
- Life expectancy less than 3 months.
- Any significant medical or psychiatric illness that would prevent the patient from giving informed consent or from following the study procedures.
- Patients with severe systemic autoimmune disease.
- Patients that do not consent to that tissue and blood samples are stored in a biobank.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01455259
Contacts
| Contact: Gustav Ullenhag, MD, PhD | +46186110000 | gustav.ullenhag@akademiska.se |
| Contact: Per Byström, MD, PhD | +46186110000 | per.bystrom@akademiska.se |
Locations
| Sweden | |
| Uppsala University Hospital | Recruiting |
| Uppsala, Sweden, 75185 | |
| Contact: Gustav Ullenhag, MD, PhD +46186110000 gustav.ullenhag@akademiska.se | |
| Contact: Per Byström, MD, PhD +46186110000 per.bystrom@akademiska.se | |
| Principal Investigator: Gustav Ullenhag, MD, PhD | |
Sponsors and Collaborators
Uppsala University
Uppsala University Hospital
Investigators
| Study Chair: | Thomas H Tötterman, MD, PhD | Uppsala University |
| Principal Investigator: | Gustav Ullenhag, MD, PhD | Uppsala University Hospital |
| Study Director: | Angelica SI Loskog, PhD | Uppsala University |
More Information
No publications provided
| Responsible Party: | Uppsala University |
| ClinicalTrials.gov Identifier: | NCT01455259 History of Changes |
| Other Study ID Numbers: | 002:CD40L |
| Study First Received: | October 11, 2011 |
| Last Updated: | October 17, 2011 |
| Health Authority: | Sweden: Medical Products Agency |
Keywords provided by Uppsala University:
|
AdCD40L Adenoviral vector CD40L CD154 malignant melanoma |
Additional relevant MeSH terms:
|
Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal |
Neoplasms by Histologic Type Neoplasms Neoplasms, Nerve Tissue Nevi and Melanomas |
ClinicalTrials.gov processed this record on May 23, 2013