Phase 2 Study of Autologous Followed by Nonmyeloablative Allogeneic Transplantation Using TLI & ATG
Condition: Transplantation, Homologous; Transplantation, Autologous; Multiple Myeloma; Blood and Marrow Transplant (BMT)
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Autologous peripheral blood stem cells (auto-PBSC) transplantation; Allogeneic peripheral blood stem cells (allo-PBSC) transplantation; Filgrastim; Cyclophosphamide; Melphalan; Cyclosporine; Total lymphoid irradiation; Rabbit anti-thymocyte globulin; Mycophenolate Mofetil 250mg; Solumedrol; Diphenhydramine; Acetaminophen; Hydrocortisone
Intervention description: Auto-PBSC ≥ 2 to 3 x 10e6 CD34+ cells/kg are intravenously (IV) infused as part of the combination stem cell therapy.
and allogeneic stem cells are administered intravenous (IV) infusion to reestablish hematopoietic function in patients whose bone marrow or immune system is damaged or defective; Allo-PBSC (target collection ≥ 5 x 10e6 CD34+ cells/kg) are intravenously (IV) infused as part of the combination stem cell therapy.; Filgrastim is administered subcutaneously (SC) at 10 µg/kg/day for auto-PBSC mobilization starting day 2 of mobilization until the last day of apheresis.
Filgrastim is administered SC at 5 µg/kg/day from Day 6 after auto-PBSC infusion to hematologic recovery.
Filgrastim is administered SC at 16 µg/kg/day for donor allo-PBSC mobilization at from Day - 4 to Day 0, prior to allo-PBSC collection.; Cyclophosphamide is administered intravenously (IV) at 4 g/m2 on Day 1 of the auto-PBSC mobilization regimen.; Melphalan is administered after CSP at 200 mg/m2 intravenously (IV) on Day -2 before auto-PBSC infusion.; Cyclosporine is administered by mouth (PO) for allo-PBSC graft vs host disease (GvHD) prophylaxis at 5 mg/kg from Day -3 through Bay +56. Tacrolimus may substituted.; Total lymphoid irradiation is administered at 80 centigrey (cGy) on Day -11 to -7; and Day -4 to -2 before alllo-PBSC infusion. TLI is also administered at 80 centigrey (cGy) x 2 on Day -1 before alllo-PBSC infusion.; ATG 1.5 mg/kg is administered intravenously (IV) on Day -11 to -7 before allo-PBSC infusion.; MMF is administered at 15 mg/kg 3x/day by mouth (PO) after allo-PBSC through Day 40, followed by 10% dose reduction weekly (dose taper) through day 96, and adjusted if there is evidence of MMF-related GI toxicity or excessive myelosuppression; Solumedrol 1 mg/kg is administered intravenously (IV) on Day -11 to -7 as a premedication for ATG and allo-PBSC infusion; Diphenhydramine 25 to 50 mg is administered as a premedication for the ATG; allo-PBSC; and DLI infusions.; Acetaminophen 650 mg is administered as a premedication for the ATG and allo-PBSC infusions.; Hydrocortisone 100 mg is administered intravenously (IV) is a premedication for the allo-PBSC and DLI infusions.
Intervention MeSH terms: Acetaminophen; Diphenhydramine; Promethazine; Cyclosporine; Mycophenolic Acid; Hydrocortisone; Methylprednisolone Hemisuccinate; Cyclophosphamide; Melphalan; Mechlorethamine; Cyclosporins; Thymoglobulin; Antilymphocyte Serum; Lenograstim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

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

Eligibility criteria:

        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