Trial Information

High-Dose Therapy and Autologous Blood Stem Cell Transplantation (ASCT) Followed by Post-Transplant Immunotherapy With Costimulated Autologous T-Cells in Conjunction With Pneumococcal Conjugate Vaccine Immunization for Patients With Multiple Myeloma

OBJECTIVES:

- Determine the feasibility of expanding ex vivo autologous T cells and infusing these
cells after high-dose chemotherapy and autologous peripheral blood stem cell rescue in
patients with multiple myeloma.

- Determine the response rate and progression-free survival of patients who receive
anti-CD3/anti-CD28 expanded autologous T cells on either day 14 or day 100
post-transplantation.

- Compare response and survival rates of these patients to historical controls.

- Determine the optimal schedule for pneumococcal conjugate vaccine (PCV) to induce an
anti-pneumococcal immune response post-transplantation in these patients.

- Determine whether "vaccine education" of antigen-presenting cells (APCs) in the stem
cell graft results in an earlier and/or enhanced immune response than with a graft
containing "non-educated" APCs in these patients.

- Determine whether an infusion of T cells presensitized to the PCV and expanded ex vivo
contributes to the anti-pneumococcal immune response in these patients.

OUTLINE: This is a randomized, multicenter study.

Patients receive cyclophosphamide IV over 12 hours on day 1 and filgrastim (G-CSF)
subcutaneously (SC) daily beginning on day 2. Patients undergo leukapheresis to collect
mononuclear cells for autologous T cells (ATCs) and peripheral blood stem cells (PBSCs).
ATCs are generated by ex vivo expansion for 8-14 days and selection for CD3+/CD28+ cells.

Patients then receive high-dose therapy comprising carmustine IV over 2 hours on day -2 and
melphalan IV over 20 minutes on day -1 or melphalan IV alone on days -2 and -1 (or day -1
only). Autologous PBSCs are reinfused on day 0. Patients also receive G-CSF SC beginning on
day 1 and continuing until blood counts recover.

Patients who choose to receive pneumococcal conjugate vaccine (PCV) are randomized to 1 of 4
treatment arms.

- Arm I: Patients receive PCV intramuscularly prior to transplantation (10-14 days before
lymphocyte collection) and post-transplantation (1 and 3 months) plus costimulated ATCs
IV over 20-60 minutes around day 12-14 post-transplantation.

- Arm II: Patients receive PCV as in arm I but receive ATCs around day 100
post-transplantation.

- Arm III: Patients receive PCV post-transplantation only (at 1 and 3 months) plus ATCs
as in arm I.

- Arm IV: Patients receive PCV as in arm III and ATCs as in arm II. Patients who choose
not to receive the PCV receive ATCs on about day 12-14 after PBSC transplantation.

All patients are offered standard pneumococcal polysaccharide vaccine at 12 months.

Patients are followed twice weekly until day 60, weekly for 4 months, monthly for 6 months,
and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 16-46 patients will be accrued for this study within 14
months.