Back to resultsCombined Bone Marrow Transplantation (BMT) and Renal Transplant for Multiple Myeloma (MM) With End Stage Renal Disease (ESRD)
Primary Purpose
Multiple Myeloma, End Stage Renal Disease
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide, anti-thymocyte globulin
Kidney transplant
Thymic irradiation
Bone marrow transplant from a related donor
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple myeloma, Renal failure, Kidney transplant
Eligibility Criteria
Recipient Inclusion Criteria
- Participants with end-stage renal failure due to or in association with greater than or equal to stage II multiple myeloma
- Males or females 18 - 65 years of age.
- Participants must have an HLA-matched or one of six HLA A, B, or DR antigen-mismatched related donor, with high resolution molecular DR allele determination.
- Men and women of reproductive potential must agree to use a reliable method of birth control during the treatment, and women should do so for a period of 2 years following the transplant.
- Participants should be on dialysis or have a CrCl <20 ml/min.
- Participants must receive medical clearance by a cardiologist prior to conditioning for transplant.
- Life expectancy greater than or equal to 6 months.
- Recipient ability to understand and provide informed consent.
Recipient Exclusion Criteria:
- Evidence of active infection as defined by: a) clinical syndrome consistent with viral or bacterial infection (e.g., influenza, URI, UTI) or b) fever with a clinical site of infection identified, or c) microbiologically documented infection, including, but not limited to, bacteremia or septicemia.
- Participation in other investigational drug use at the time of enrollment.
- Contraindication to therapy with any one of the proposed agents (e.g., history of allergy to horse serum in ATG).
- Serologic positivity to HIV, HCV, or HbsAg positivity.
- Women of childbearing age in whom adequate contraception cannot be maintained.
- Malignancy within the past two years other than multiple myeloma, excluding basal cell carcinoma of the skin and carcinoma in situ of the cervix.
- AST/ALT > 3 x normal or bilirubin > 1.5 x normal (unless due to Gilbert's syndrome).
- Pregnancy or uncontrolled serious medical illness not related to underlying myeloma.
- Cardiac ejection fraction < 40% by echocardiogram; individual assessment if ejection fraction between 40% and 50%.
- FEV1 < 50% predicted or corrected DLCO < 50% predicted.
- ABO blood group incompatibility in the host-vs-graft direction.
Donor Inclusion Criteria:
- HLA-matched or one of six HLA A, B, or DR antigen-mismatched related male or female donor 18-65 years of age.
- ECOG performance status 0 or 1.
- Excellent health per conventional pre-donor history (medical and psychosocial evaluation).
- Acceptable laboratory parameters (hematology in normal or near-normal range; liver function < 2 times the upper limit of normal and normal creatinine).
- Compatible ABO blood group.
- Negative donor lymphocyte crossmatch.
- No positive testing for viral infection (HbsAg, HIV, HCV, HTLV-1).
- Cardiac/Pulmonary evaluation within normal limits (CXR, EKG).
- Donor ability to understand and provide informed consent.
Sites / Locations
- Massachusetts General Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Bone marrow and renal transplant
Arm Description
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
Outcomes
Primary Outcome Measures
Remission status of multiple myeloma
Renal allograft acceptance and ability to discontinue immunosuppressive therapy
Secondary Outcome Measures
Graft versus host disease (GVHD)
Opportunistic infections
T cell recovery and immune reconstitution
Full Information
NCT ID
NCT00854139
First Posted
February 27, 2009
Last Updated
March 2, 2020
Sponsor
Massachusetts General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT00854139
Brief Title
Combined Bone Marrow Transplantation (BMT) and Renal Transplant for Multiple Myeloma (MM) With End Stage Renal Disease (ESRD)
Official Title
Combined HLA-matched Bone Marrow and Kidney Transplantation for Multiple Myeloma With Renal Failure
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
August 2001 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
July 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma, End Stage Renal Disease
Keywords
Multiple myeloma, Renal failure, Kidney transplant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bone marrow and renal transplant
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide, anti-thymocyte globulin
Other Intervention Name(s)
Cyclosporine
Intervention Description
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
Intervention Type
Procedure
Intervention Name(s)
Kidney transplant
Intervention Description
On Day 0 the renal transplant is performed according to standard surgical techniques, preferably using an iliac fossa, extraperitoneal approach
Intervention Type
Radiation
Intervention Name(s)
Thymic irradiation
Intervention Description
Thymic irradiation 7 Gy on Day -1
Intervention Type
Procedure
Intervention Name(s)
Bone marrow transplant from a related donor
Intervention Description
• 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
Primary Outcome Measure Information:
Title
Remission status of multiple myeloma
Time Frame
3 years
Title
Renal allograft acceptance and ability to discontinue immunosuppressive therapy
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Graft versus host disease (GVHD)
Time Frame
3 years
Title
Opportunistic infections
Time Frame
3 years
Title
T cell recovery and immune reconstitution
Time Frame
3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Recipient Inclusion Criteria
Participants with end-stage renal failure due to or in association with greater than or equal to stage II multiple myeloma
Males or females 18 - 65 years of age.
Participants must have an HLA-matched or one of six HLA A, B, or DR antigen-mismatched related donor, with high resolution molecular DR allele determination.
Men and women of reproductive potential must agree to use a reliable method of birth control during the treatment, and women should do so for a period of 2 years following the transplant.
Participants should be on dialysis or have a CrCl <20 ml/min.
Participants must receive medical clearance by a cardiologist prior to conditioning for transplant.
Life expectancy greater than or equal to 6 months.
Recipient ability to understand and provide informed consent.
Recipient Exclusion Criteria:
Evidence of active infection as defined by: a) clinical syndrome consistent with viral or bacterial infection (e.g., influenza, URI, UTI) or b) fever with a clinical site of infection identified, or c) microbiologically documented infection, including, but not limited to, bacteremia or septicemia.
Participation in other investigational drug use at the time of enrollment.
Contraindication to therapy with any one of the proposed agents (e.g., history of allergy to horse serum in ATG).
Serologic positivity to HIV, HCV, or HbsAg positivity.
Women of childbearing age in whom adequate contraception cannot be maintained.
Malignancy within the past two years other than multiple myeloma, excluding basal cell carcinoma of the skin and carcinoma in situ of the cervix.
AST/ALT > 3 x normal or bilirubin > 1.5 x normal (unless due to Gilbert's syndrome).
Pregnancy or uncontrolled serious medical illness not related to underlying myeloma.
Cardiac ejection fraction < 40% by echocardiogram; individual assessment if ejection fraction between 40% and 50%.
FEV1 < 50% predicted or corrected DLCO < 50% predicted.
ABO blood group incompatibility in the host-vs-graft direction.
Donor Inclusion Criteria:
HLA-matched or one of six HLA A, B, or DR antigen-mismatched related male or female donor 18-65 years of age.
ECOG performance status 0 or 1.
Excellent health per conventional pre-donor history (medical and psychosocial evaluation).
Acceptable laboratory parameters (hematology in normal or near-normal range; liver function < 2 times the upper limit of normal and normal creatinine).
Compatible ABO blood group.
Negative donor lymphocyte crossmatch.
No positive testing for viral infection (HbsAg, HIV, HCV, HTLV-1).
Cardiac/Pulmonary evaluation within normal limits (CXR, EKG).
Donor ability to understand and provide informed consent.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas R Spitzer, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Combined Bone Marrow Transplantation (BMT) and Renal Transplant for Multiple Myeloma (MM) With End Stage Renal Disease (ESRD)
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