Phase 2 Study of Autologous Followed by Nonmyeloablative Allogeneic Transplantation Using TLI & ATG

A Phase 2 Study of Autologous Followed by Nonmyeloablative Allogeneic Transplantation Using Total Lymphoid Irradiation (TLI) and Antithymocyte Globulin (ATG) in Multiple Myeloma Patients

To evaluate the toxicity and tolerability of this tandem autologous/allogeneic transplant approach for patients with advanced stage multiple myeloma.

Development of cell-based immunotherapy from allogeneic hematopoietic cell transplantation (HCT) is dependent upon stable T-cell engraftment and the success of this therapeutic approach is likely to be greatest when directed against a minimal rather than gross tumor burden. To this end, tandem transplants with high dose therapy and autologous hematopoietic cell transplantation (AHCT) for tumor cytoreduction followed by non-myeloablative allotransplant have been conducted. In myeloma, this tandem approach results in greater efficacy compared to conventional AHCT.

PARTICIPANT INCLUSION CRITERIA

• Stage II-III multiple myeloma or have progression after initial treatment of Stage I disease (Durie Salmon Staging). Patients with plasma cell leukemia are also included.
• Multiple myeloma / plasma cell leukemia diagnosis confirmed by pathology reviewed at Stanford University Medical Center.
• 18 to ≤ 75 years of age
• Karnofsky Performance Status > 70%.
• Corrected Carbon monoxide diffusing capacity (Dlco) > 60%
• Left ventricle ejection fraction (LVEF) > 50%.
• Alanine aminotransferase (ALT) ≤ 2 x normal
• Aspartate aminotransferase (AST) ≤ 2 x normal
• Total bilirubin ≤ 2 mg/dL, unless hemolysis or Gilbert's disease.
• Estimated creatinine clearance > 50 mL/min.
• Identified related or unrelated Human leukocyte antigen (HLA)-identical donor or donor with one antigen/allele mismatch in (HLA-A, B, C or DRB1).
• Signed informed consent.

DONOR INCLUSION CRITERIA

• At least 17 years of age
• HIV-seronegative
• Must be capable of giving signed, informed consent
• No contraindication to the administration of filgrastim
• Willing to have a central venous catheter placed for apheresis if peripheral veins are inadequate

PARTICIPANT EXCLUSION CRITERIA

• Prior allogeneic hematopoietic cell transplantation
• Uncontrolled active infection
• Uncontrolled congestive heart failure or angina
• HIV-positive
• Pregnant or nursing

DONOR EXCLUSION CRITERIA

• Serious medical or psychological illness
• Pregnant or lactating
• Prior malignancies within the last 5 years except for non-melanoma skin cancers