Combined Bone Marrow Transplantation (BMT) and Renal Transplant for Multiple Myeloma (MM) With End Stage Renal Disease (ESRD)
Condition: Multiple Myeloma; End Stage Renal Disease
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Kidney Diseases; Kidney Failure, Chronic
Study type: Interventional
Phase: Phase 1

Summary: 
      The primary objective is to cure multiple myeloma with less toxic allogeneic bone marrow
      transplantation while inducing renal allograft tolerance through mixed chimerism in patients
      with end stage renal failure and multiple myeloma
    

Detailed description: 
      The induction of transplantation tolerance involves the specific elimination of the immune
      response to the transplant but not to other antigens. In the realm of kidney transplantation,
      tolerance means that the recipient is unable to detect the donor transplant kidney as
      foreign, and therefore the recipient is unable to reject the kidney. Donor bone marrow
      engraftment leads to kidney graft tolerance in animal models. Renal failure is a major
      complication of multiple myeloma, a plasma cell malignancy for which the only known cure is
      allogeneic bone marrow transplantation. Standard bone marrow transplantation is associated
      with frequent toxicity in patients with multiple myeloma, and is generally no considered an
      option for those patients with end stage renal disease. Myeloma patients are excluded from
      conventional renal transplantation protocols because of their underlying malignancy. A less
      toxic bone marrow transplantation protocol, combined with renal transplantation, could
      provide an opportunity for cure of the myeloma and correction of ESRD in patients with this
      disease. In addition, successful marrow engraftment may be expected to lead to a state of
      tolerance. Successful implementation of tolerance would be a major benefit to transplant
      recipients. The significance of developing tolerance is that the patient would be spared the
      disabling complications of indefinite immunosuppression, which include infections, cataracts,
      osteoporosis, diabetes, atherosclerosis, hypertension, and malignancy
    

Intervention name(s): Cyclophosphamide, anti-thymocyte globulin; Kidney transplant; Thymic irradiation; Bone marrow transplant from a related donor
Intervention type(s): Drug; Procedure; Radiation; Procedure
Intervention description(s): Cyclophosphamide 60 mg/kg IV on Day -5, -4 Anti-thymocyte globulin 20 mg/kg IV on Day -1, Day +1, +3, +5
Cyclosporine starting on Day -1 at 5 mg/kg daily I.V. and reduced to 3 mg/kg on Day +4, and adjusted to provide a trough whole blood concentration of 250-400 ng/mL. The route of administration will be changed to oral as soon as the patient is able to tolerate oral medications; On Day 0 the renal transplant is performed according to standard surgical techniques, preferably using an iliac fossa, extraperitoneal approach; Thymic irradiation 7 Gy on Day -1; • Donor bone marrow (> 2 x 108 nucleated cells/kg of recipient body weight) is prepared for infusion according to the standard procedure at the medical center. A total of 15,000 Units of heparin is mixed with the marrow, which is infused at a rate of 300-500 cc/hr. The infusion begins in the operating room as soon as the vascular anastomosis of the renal allograft has been completed. Protamine, 25 mg, is administered I.V. after completion of the first half of the bone marrow infusion. If a partial thromboplastin time measured after completion of the marrow infusion is > 60 seconds, the protamine treatment shall be repeated
Other intervention name(s): Cyclosporine
Intervention MeSH terms: Cyclosporine; Cyclophosphamide; Cyclosporins; Antilymphocyte Serum
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Multiple myeloma; Renal failure; Kidney transplant