Phase I/II Clinical Trial Combining hTERT Tumor Vaccine & Autologous T Cells in Patients With Advanced Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is:

        1. 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.

        2. 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.
    

Detailed description: 
      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:

        1. 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).

        2. 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.
    

Intervention name(s): hTERT vaccine, GM-CSF, PCV, T cell infusion; GM-CSF, PCV, T cell infusion
Intervention type(s): Biological; Biological
Intervention description(s): hTERT vaccine (multi-peptide vaccine), Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), Prevnar-Pneumococcal Conjugate vaccine (PCV), T cell infusion; Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), Prevnar-Pneumococcal Conjugate vaccine (PCV), T cell infusion
Intervention MeSH terms: Molgramostim; Sargramostim
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment