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

NCT00854139 | Completed Phase 1 DMC

• 1 other identifier: NKD01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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

Conditions

Multiple Myeloma; End Stage Renal Disease

Keywords

Multiple myeloma; Renal failure; Kidney transplant

Outcome Measures

Primary Outcomes (2)

• Remission status of multiple myeloma

  3 years

• Renal allograft acceptance and ability to discontinue immunosuppressive therapy

  3 years

Secondary Outcomes (3)

• Graft versus host disease (GVHD)

  3 years

• Opportunistic infections

  3 years

• T cell recovery and immune reconstitution

  3 years

Study Arms (1)

Bone marrow and renal transplant

EXPERIMENTAL

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; Procedure: Kidney transplant; Radiation: Thymic irradiation; Procedure: Bone marrow transplant from a related donor

Interventions

Cyclophosphamide, anti-thymocyte globulin DRUG

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

Also known as: Cyclosporine

Bone marrow and renal transplant

Kidney transplant PROCEDURE

On Day 0 the renal transplant is performed according to standard surgical techniques, preferably using an iliac fossa, extraperitoneal approach

Bone marrow and renal transplant

Thymic irradiation RADIATION

Thymic irradiation 7 Gy on Day -1

Bone marrow and renal transplant

Bone marrow transplant from a related donor PROCEDURE

• 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

Bone marrow and renal transplant

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Kidney Failure, Chronic; Renal Insufficiency

Interventions

Cyclophosphamide; Antilymphocyte Serum; Cyclosporine; Kidney Transplantation

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Renal Insufficiency, Chronic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Renal Replacement Therapy; Therapeutics; Organ Transplantation; Transplantation; Surgical Procedures, Operative; Urologic Surgical Procedures; Urogenital Surgical Procedures

Study Officials

• Thomas R Spitzer, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 27, 2009
• First Posted: March 3, 2009
• Study Start: August 1, 2001
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: March 4, 2020

Record last verified: 2020-03

Locations

US (1)