Chemotherapy and Peripheral Stem Cell Transplantation Followed By Immunotherapy in Treating Patients With Multiple Myeloma
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with autologous peripheral stem cell transplantation and immunotherapy may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing.
PURPOSE: Randomized phase I/II trial to study the effectiveness of combining chemotherapy with peripheral stem cell transplantation followed by immunotherapy in treating patients who have multiple myeloma.
|Infection Multiple Myeloma and Plasma Cell Neoplasm||Biological: filgrastim Biological: pneumococcal polyvalent vaccine Biological: therapeutic autologous lymphocytes Biological: therapeutic tumor infiltrating lymphocytes Drug: carmustine Drug: cyclophosphamide Drug: melphalan Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation||Phase 1 Phase 2|
|Study Design:||Allocation: Randomized
Primary Purpose: Treatment
|Official Title:||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|
|Study Start Date:||December 2001|
|Study Completion Date:||February 2008|
|Primary Completion Date:||November 2004 (Final data collection date for primary outcome measure)|
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00046852
|United States, Maryland|
|Marlene and Stewart Greenebaum Cancer Center, University of Maryland|
|Baltimore, Maryland, United States, 21201|
|United States, Pennsylvania|
|Abramson Cancer Center of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104-4283|
|Study Chair:||Aaron P. Rapoport, MD||University of Maryland Greenebaum Cancer Center|