Clinical trial NCT02158052
Conditions: Multiple Myeloma Amyloidosis
Keywords: HLA matched bone marrow transplantation kidney transplantation
Sponsor: Massachusetts General Hospital
Start date: 2015-02-01; Completion date: 2021-06-22
Enrollment: 2 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This pilot trial offers the unique opportunity for both the treatment of multiple myeloma or systemic AL amyloidosis for which hematopoietic stem cell transplantation would be ordinarily indicated and the reversal of end-stage renal failure, while avoiding the risks associated with long-term standard anti-rejection therapy used in renal transplantation. The primary objectives of this study are to assess renal allograft tolerance (that is, the acceptance of the kidney without the need for anti-rejection therapy), assess anti-tumor response rates in multiple myeloma and AL amyloidosis, and assess complication rates for genetically (HLA) matched related donor combined bone marrow and kidney transplantation using a low dose total body irradiation based preparative regimen.

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 and AL amyloidosis for which the only known cure is allogeneic bone marrow transplantation. Standard bone marrow transplantation is associated with prohibitive toxicities in patients with end stage renal disease, and is generally not considered an option for those patients. Patients with multiple myeloma and AL amyloidosis are excluded from conventional renal transplantation protocols because of their underlying malignancy. A less toxic bone marrow transplantation protocol, utilizing low dose total body irradiation and anti-thymocyte globulin, combined with renal transplantation, could provide an opportunity for cure of the myeloma or amyloidosis and correction of end stage renal 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 could be spared the disabling complications of indefinite immunosuppression, which include infections, cataracts, osteoporosis, diabetes, atherosclerosis, hypertension, and malignancy.

Arms: arm 1: combined bone marrow and kidney transplantation arm 2: Donors who donate bone marrow and kidney
Interventions: intervention 1: Tacrolimus intervention 2: Equine Anti-thymocyte globulin intervention 3: Kidney transplant from a related donor intervention 4: Bone marrow transplant from a related donor intervention 5: Total body irradiation 400 centigray (200 cGy X 2)
Intervention descriptions: intervention 1: Tacrolimus starting on Day -1 intervention 2: 20 mg/kg IV on Days -3, -1, +1, +3 intervention 3: On Day 0 the renal transplant is performed according to standard surgical techniques. intervention 4: Donor bone marrow (\> 2 x 10e8 nucleated cells/kg of recipient body weight) is prepared for infusion according to the standard procedure. The infusion begins in the operating room as soon as the vascular anastomosis of the renal allograft has been completed. intervention 5: On transplant day -1

Protocol documents:
Prot_SAP_000.pdf: