Phase I/IIa AdCD40L Immunogene Therapy for Malignant Melanoma
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.
|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.|
- 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).
- 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 ]
|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)|
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.
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.
|Contact: Gustav Ullenhag, MD, PhDfirstname.lastname@example.org|
|Contact: Per Byström, MD, PhDemail@example.com|
|Uppsala University Hospital||Recruiting|
|Uppsala, Sweden, 75185|
|Contact: Gustav Ullenhag, MD, PhD +46186110000 firstname.lastname@example.org|
|Contact: Per Byström, MD, PhD +46186110000 email@example.com|
|Principal Investigator: Gustav Ullenhag, MD, PhD|
|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|