Combined Bone Marrow Transplantation (BMT) and Renal Transplant for Multiple Myeloma (MM) With End Stage Renal Disease (ESRD)
Information source: Massachusetts General Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Multiple Myeloma; End Stage Renal Disease
Intervention: Cyclophosphamide, anti-thymocyte globulin (Drug); Kidney transplant (Procedure); Thymic irradiation (Radiation); Bone marrow transplant from a related donor (Procedure)
Phase: Phase 1
Status: Completed
Sponsored by: Massachusetts General Hospital Official(s) and/or principal investigator(s): Thomas R Spitzer, MD, Principal Investigator, Affiliation: Massachusetts General Hospital
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
Clinical Details
Official title: Combined HLA-matched Bone Marrow and Kidney Transplantation for Multiple Myeloma With Renal Failure
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Remission status of multiple myelomaRenal allograft acceptance and ability to discontinue immunosuppressive therapy
Secondary outcome: Graft versus host disease (GVHD)Opportunistic infections T cell recovery and immune reconstitution
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
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Recipient Inclusion Criteria
1. Participants with end-stage renal failure due to or in association with greater than
or equal to stage II multiple myeloma
2. Males or females 18 - 65 years of age.
3. 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.
4. 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.
5. Participants should be on dialysis or have a CrCl <20 ml/min.
6. Participants must receive medical clearance by a cardiologist prior to conditioning
for transplant.
7. Life expectancy greater than or equal to 6 months.
8. Recipient ability to understand and provide informed consent.
Recipient Exclusion Criteria:
1. 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.
2. Participation in other investigational drug use at the time of enrollment.
3. Contraindication to therapy with any one of the proposed agents (e. g., history of
allergy to horse serum in ATG).
4. Serologic positivity to HIV, HCV, or HbsAg positivity.
5. Women of childbearing age in whom adequate contraception cannot be maintained.
6. Malignancy within the past two years other than multiple myeloma, excluding basal
cell carcinoma of the skin and carcinoma in situ of the cervix.
7. AST/ALT > 3 x normal or bilirubin > 1. 5 x normal (unless due to Gilbert's syndrome).
8. Pregnancy or uncontrolled serious medical illness not related to underlying myeloma.
9. Cardiac ejection fraction < 40% by echocardiogram; individual assessment if ejection
fraction between 40% and 50%.
10. FEV1 < 50% predicted or corrected DLCO < 50% predicted.
11. ABO blood group incompatibility in the host-vs-graft direction.
Donor 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.
Locations and Contacts
Massachusetts General Hospital, Boston, Massachusetts 02114, United States
Additional Information
Starting date: August 2001
Last updated: April 13, 2015
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