Combined Bone Marrow Transplantation (BMT) and Renal Transplant for Multiple Myeloma (MM) With End Stage Renal Disease (ESRD)

Phase 1

Completed

• Conditions: End Stage Renal Disease; Multiple Myeloma
• Interventions: Drug: Cyclophosphamide, anti-thymocyte globulin; Procedure: Kidney transplant; Radiation: Thymic irradiation; Procedure: Bone marrow transplant from a related donor

• Registration Number: NCT00854139
• Lead Sponsor: Massachusetts General Hospital

Brief 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

Study Timeline

• Study Start: 2001-08
• Study First Submitted: 2009-02-27
• Study First Submitted QC: 2009-03-02
• Study First Posted: 2009-03-03
• Primary Completion: 2014-07
• Study Completion: 2014-07
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-02
• Last Update Posted: 2020-03-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

1. HLA-matched or one of six HLA A, B, or DR antigen-mismatched related male or female donor 18-65 years of age.
2. ECOG performance status 0 or 1.
3. Excellent health per conventional pre-donor history (medical and psychosocial evaluation).
4. Acceptable laboratory parameters (hematology in normal or near-normal range; liver function < 2 times the upper limit of normal and normal creatinine).
5. Compatible ABO blood group.
6. Negative donor lymphocyte crossmatch.
7. No positive testing for viral infection (HbsAg, HIV, HCV, HTLV-1).
8. Cardiac/Pulmonary evaluation within normal limits (CXR, EKG).
9. Donor ability to understand and provide informed consent.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bone marrow and renal transplant	Kidney transplant	Cyclophosphamide, anti-thymocyte globulin, thymic irradiation conditioning and kidney transplant and bone marrow transplant from a related donor for patients with multiple myeloma and end stage renal disease with cyclosporine for graft versus host disease prophylaxis
Bone marrow and renal transplant	Cyclophosphamide, anti-thymocyte globulin	Cyclophosphamide, anti-thymocyte globulin, thymic irradiation conditioning and kidney transplant and bone marrow transplant from a related donor for patients with multiple myeloma and end stage renal disease with cyclosporine for graft versus host disease prophylaxis
Bone marrow and renal transplant	Bone marrow transplant from a related donor	Cyclophosphamide, anti-thymocyte globulin, thymic irradiation conditioning and kidney transplant and bone marrow transplant from a related donor for patients with multiple myeloma and end stage renal disease with cyclosporine for graft versus host disease prophylaxis
Bone marrow and renal transplant	Thymic irradiation	Cyclophosphamide, anti-thymocyte globulin, thymic irradiation conditioning and kidney transplant and bone marrow transplant from a related donor for patients with multiple myeloma and end stage renal disease with cyclosporine for graft versus host disease prophylaxis

Primary Outcome Measures

Name	Time	Method
Remission status of multiple myeloma	3 years
Renal allograft acceptance and ability to discontinue immunosuppressive therapy	3 years

Secondary Outcome Measures

Name	Time	Method
Graft versus host disease (GVHD)	3 years
Opportunistic infections	3 years
T cell recovery and immune reconstitution	3 years

Trial Locations

Locations (1)

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