Combined Bone Marrow and Renal Transplantation for Hematologic Disorders With End Stage Renal Disease

Not Applicable

Completed

• Conditions: Multiple Myeloma; Amyloidosis
• Interventions: Drug: Tacrolimus; Drug: Equine Anti-thymocyte globulin; Procedure: Kidney transplant from a related donor; Drug: Bone marrow transplant from a related donor; Radiation: Total body irradiation 400 centigray (200 cGy X 2)

• Registration Number: NCT02158052
• Lead Sponsor: Massachusetts General Hospital

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.

Study Timeline

• Study First Submitted: 2014-05-30
• Study First Submitted QC: 2014-06-05
• Study First Posted: 2014-06-06
• Study Start: 2015-02
• Primary Completion: 2021-06-22
• Study Completion: 2021-06-22
• Results First Submitted: 2022-08-31
• Status Verified: 2022-11
• Results First Submitted QC: 2022-11-14
• Last Update Submitted: 2022-11-14
• Results First Posted: 2022-12-13
• Last Update Posted: 2022-12-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bone Marrow and Kidney RECIPIENTS	Total body irradiation 400 centigray (200 cGy X 2)	combined bone marrow and kidney transplantation
Bone Marrow and Kidney RECIPIENTS	Bone marrow transplant from a related donor	combined bone marrow and kidney transplantation
Bone Marrow and Kidney RECIPIENTS	Equine Anti-thymocyte globulin	combined bone marrow and kidney transplantation
Bone Marrow and Kidney RECIPIENTS	Kidney transplant from a related donor	combined bone marrow and kidney transplantation
Bone Marrow and Kidney DONORS	Kidney transplant from a related donor	Donors who donate bone marrow and kidney
Bone Marrow and Kidney RECIPIENTS	Tacrolimus	combined bone marrow and kidney transplantation

Primary Outcome Measures

Name	Time	Method
Number of Participants Without Renal Allograft Rejection at 6 Months Post-transplant	6 Months	The Primary Outcome is: the incidence of renal allograft rejection at 6 months post-transplant

Secondary Outcome Measures

Name	Time	Method
Anti-Tumor Response Rate	3 years	This is measurement is summarized via bone marrow biopsy results and blood assays through 3 years.; Anti-tumor response is assessed according to Center for International Blood and Marrow Transplant Research (CIBMTR.org) criteria.; For multiple myeloma, based on assessment of serum and urine immunofixation, the presence or absence of soft tissue plasmacytomas and analyses of bone marrow aspirate and biopsy samples, response categories include stringent complete remission (sCR), complete remission (CR), near CR (nCR) very good partial response (VGPR), partial response (PR), stable disease (SD), and progressive disease (PD).; For AL amyloidosis, based on assessment of serum and urine immunofixation and serum free light chain ratio, hematologic response categories include complete response, very good partial response, partial response, no response/stable disease and progressive disease. Organ responses are also assessed according to organ specific criteria.

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States