Chemotherapy and Peripheral Stem Cell Transplantation Followed By Immunotherapy in Treating 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.

DISEASE CHARACTERISTICS:

• Diagnosis of multiple myeloma requiring systemic treatment
• No obvious myelodysplastic changes in the marrow

PATIENT CHARACTERISTICS:

Age

• 18 to 80

Performance status

• ECOG 0-2 (ECOG 3-4 allowed if based solely on bone pain)

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• No chronic active hepatitis
• No liver cirrhosis

Renal

• Creatinine no greater than 3.0 mg/dL
• No dialysis

Cardiovascular

• LVEF at least 45% unless no evidence of untreated clinically significant functional impairment

Pulmonary

• FEV_1 and FVC at least 50% of predicted
• Total lung capacity at least 50% of predicted
• DLCO at least 50% of predicted
• Mild to moderate pulmonary impairment (lower DLCO) allowed but patients would not receive study carmustine
• Patients unable to complete pulmonary function test due to bone pain or fracture must have high-resolution CT scan of the chest and arterial partial pressure of oxygen greater than 70

Other

• No active infections requiring IV antibiotics
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Prior pulse dexamethasone (1-2 courses) allowed
• Concurrent pulse dexamethasone allowed during mobilization therapy

Radiotherapy

• Not specified

Surgery

• Not specified