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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
Thomas Spitzer, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00854139
First received: February 27, 2009
Last updated: March 31, 2014
Last verified: March 2014
  Purpose

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


Condition Intervention Phase
Multiple Myeloma
End Stage Renal Disease
Drug: Cyclophosphamide, anti-thymocyte globulin
Procedure: Kidney transplant
Radiation: Thymic irradiation
Procedure: Bone marrow transplant from a related donor
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Combined HLA-matched Bone Marrow and Kidney Transplantation for Multiple Myeloma With Renal Failure

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Remission status of multiple myeloma [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Renal allograft acceptance and ability to discontinue immunosuppressive therapy [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Graft versus host disease (GVHD) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Opportunistic infections [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • T cell recovery and immune reconstitution [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: August 2001
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bone marrow and renal 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
Drug: Cyclophosphamide, anti-thymocyte globulin

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

Other Name: Cyclosporine
Procedure: Kidney transplant
On Day 0 the renal transplant is performed according to standard surgical techniques, preferably using an iliac fossa, extraperitoneal approach
Radiation: Thymic irradiation
Thymic irradiation 7 Gy on Day -1
Procedure: Bone marrow transplant from a related donor
• 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

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00854139

Contacts
Contact: Thomas R Spitzer, MD 617-724-9191 tspitzer@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Thomas R Spitzer, MD    617-724-9191    tspitzer@partners.org   
Sub-Investigator: Megan Sykes, MD         
Sub-Investigator: A. B Cosimi, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Thomas R Spitzer, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Thomas Spitzer, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00854139     History of Changes
Other Study ID Numbers: NKD01
Study First Received: February 27, 2009
Last Updated: March 31, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Multiple myeloma
Renal failure
Kidney transplant

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Renal Insufficiency
Renal Insufficiency, Chronic
Urologic Diseases
Vascular Diseases
Antilymphocyte Serum
Cyclophosphamide
Cyclosporine
Cyclosporins
Alkylating Agents
Anti-Infective Agents
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on October 20, 2014