Phase I/II Clinical Trial Combining hTERT Tumor Vaccine & Autologous T Cells in Patients With Advanced Myeloma
The purpose of this study is:
- To evaluate the safety of activated T cell infusions and immunization with hTERT multi-peptide vaccine in the post-transplant setting and whether the combination can delay hematopoietic recovery or induce other autoimmune events.
- To determine whether the strategy of infusing vaccine-primed T-cells early after transplant in conjunction with post-transplant boosters leads to the induction of cellular immune responses to hTERT.
|Multiple Myeloma||Biological: Telomerase (hTERT vaccine + pneumococcal conjugate vaccine (PCV)) Biological: PCV vaccine||Phase 1 Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase I/II Combination Immunotherapy After ASCT for Advanced Myeloma to Study HTERT Vaccination Followed by Adoptive Transfer of Vaccine-Primed Autologous T Cells|
- Does combination therapy delay hematopoietic recovery or induce other autoimmune events. [ Time Frame: 2 yrs ]
- Does combination therapy generate cytotoxic T-cell responses to autologous myeloma cells in-vivo. [ Time Frame: 2 yrs ]
|Study Start Date:||December 2006|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Experimental: ARM A
ARM A Injection 1 and 2 the telomerase vaccination, followed by GM-CSF, which will also be injected at the same site in order to make the vaccinations work better.
Injection 3 and 4 (deep part of the skin in the left thigh)- the survivin and CMV vaccination, followed by GM-CSF.
Injection 5 - the PCV vaccination.
Biological: Telomerase (hTERT vaccine + pneumococcal conjugate vaccine (PCV))
One vaccination prior to autologous transplant and 3 vaccination after autologous transplant.
Active Comparator: ARM B
ARM B Injection 1: PCV vaccination Injection 2 GM-CSF injection Injection 3 : GM-CSF injection
Biological: PCV vaccine
Receipt of PCV vaccine and GM-CSF injections prior to autologous transplant and post transplant
This protocol proposes to combine two different investigational products to test the hypothesis that autologous T cell therapy can augment the potency of a putative tumor vaccine post- stem cell transplant, and lead to a myeloma-directed T-cell mediated "graft vs. myeloma" effect in patients with advance myeloma. The hope is that this combination therapy approach will result in a more rapid recovery of acquired immunity and consequently increased cure rates and better clinical outcomes. The two investigational products to be evaluated in this Phase I/II study include:
- hTERT Vaccine (the putative tumor vaccine)- a multi-peptide vaccine consisting of 3 peptides against the catalytic subunit of telomerase (hTERT D988Y, I540, and R572Y), 1 survivin peptide (Sur1M2- an antiapoptotic protein), and 1 CMV (cytopeptide (N495).
- T cell therapy- T-cells isolated from the patient and activated/expanded ex vivo by antiCD3/28 beads.
This is a two-site study at the University of Pennsylvania and University of Maryland to recruit a total of fifty-six study patients. The key eligibility criteria are patients who have systemic or multifocal myeloma requiring autologous stem cell transplantation. After enrollment, patients will be divided into two arms (A and B) according to their HLA A2 status (A = HLA A2 +, B = HLA A2-). Patients in ARM A will be initially immunized with the hTERT vaccine along with a pneumococcal conjugate vaccine (PCV); patients in ARM B will be initially immunized and given boosters of PCV only. All patients will undergo T-cell harvest, stem cell mobilization and collection, high-dose chemotherapy, autologous stem cell transplant (ASCT), and an infusion of expanded T cells at day 2 after ASCT. Patients in ARM A will then receive three hTERT/PCV vaccine boosters at day 14, 42, and 90 after ASCT.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00834665
|United States, Maryland|
|Greenbaum Cancer Center|
|Baltimore, Maryland, United States, 21201|
|United States, Pennsylvania|
|University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Study Chair:||Carl H June, MD||University of Pennsylvania|