Combined Bone Marrow and Renal Transplantation for Hematologic Disorders With End Stage Renal Disease

NCT02158052 | Completed Results DMC

• 1 other identifier: KdBMT-2
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot trial offers the unique opportunity for both the treatment of multiple myeloma or systemic AL amyloidosis for which hematopoietic stem cell transplantation would be ordinarily indicated and the reversal of end-stage renal failure, while avoiding the risks associated with long-term standard anti-rejection therapy used in renal transplantation. The primary objectives of this study are to assess renal allograft tolerance (that is, the acceptance of the kidney without the need for anti-rejection therapy), assess anti-tumor response rates in multiple myeloma and AL amyloidosis, and assess complication rates for genetically (HLA) matched related donor combined bone marrow and kidney transplantation using a low dose total body irradiation based preparative regimen.

Conditions

Multiple Myeloma; Amyloidosis

Keywords

HLA matched; bone marrow transplantation; kidney transplantation

Outcome Measures

Primary Outcomes (1)

• Number of Participants Without Renal Allograft Rejection at 6 Months Post-transplant

  The Primary Outcome is: the incidence of renal allograft rejection at 6 months post-transplant

  6 Months

Secondary Outcomes (1)

• Anti-Tumor Response Rate

  3 years

Study Arms (2)

Bone Marrow and Kidney RECIPIENTS

EXPERIMENTAL

combined bone marrow and kidney transplantation

Drug: Tacrolimus; Drug: Equine Anti-thymocyte globulin; Procedure: Kidney transplant from a related donor; Drug: Bone marrow transplant from a related donor; Radiation: Total body irradiation 400 centigray (200 cGy X 2)

Bone Marrow and Kidney DONORS

OTHER

Donors who donate bone marrow and kidney

Procedure: Kidney transplant from a related donor

Interventions

Tacrolimus DRUG

Tacrolimus starting on Day -1

Bone Marrow and Kidney RECIPIENTS

Equine Anti-thymocyte globulin DRUG

20 mg/kg IV on Days -3, -1, +1, +3

Bone Marrow and Kidney RECIPIENTS

Kidney transplant from a related donor PROCEDURE

On Day 0 the renal transplant is performed according to standard surgical techniques.

Bone Marrow and Kidney DONORS; Bone Marrow and Kidney RECIPIENTS

Bone marrow transplant from a related donor DRUG

Donor bone marrow (\> 2 x 10e8 nucleated cells/kg of recipient body weight) is prepared for infusion according to the standard procedure. The infusion begins in the operating room as soon as the vascular anastomosis of the renal allograft has been completed.

Bone Marrow and Kidney RECIPIENTS

Total body irradiation 400 centigray (200 cGy X 2) RADIATION

On transplant day -1

Bone Marrow and Kidney RECIPIENTS

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 multiple myeloma or systemic AL amyloidosis which hematopoietic cell transplantation is appropriate and a ≥ 50% five-year survival probability with transplantation is expected. This includes, but is not limited to:
• Multiple myeloma (MM), ISS stage II or III in complete or very good partial remission
• AL amyloidosis without significant cardiac disease
• 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 class I and II allele typing.
• 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.
• Patients should not have evidence of renal recovery of their renal failure over a 90 day period of therapy for their underlying malignancy or other blood disorder.
• Patients with a history of other malignancies excluding basal cell carcinoma of the skin and carcinoma in situ of the cervix with a disease-free survival interval of \>2 years. Patients with the following malignancies must demonstrate a 5 year disease-free survival:
• Breast cancer with positive nodes
• Malignant melanoma (other than in situ)
• Colorectal cancer (other than Dukes Stage A or B1)
• Patients with multiple myeloma must have received previous treatment with a bortezomib-based regimen.
• Patients with AL amyloidosis must have received previous treatment with a bortezomib-based regimen and/or autologous stem cell transplantation
• Patients with a history of malignant melanoma must be reviewed by an independent oncologist prior to enrollment.

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 or HCV.
• Women of childbearing age in whom adequate contraception cannot be maintained.
• 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.
• FEV1 \< 50% predicted or corrected DLCO \< 50% predicted.
• ABO blood group incompatibility in the host-vs-graft direction.
• Diagnosis of myelodysplastic syndrome
• 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; Amyloidosis

Interventions

Tacrolimus; Antilymphocyte Serum

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; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Thomas Spitzer, MD
• Organization: Massachusetts General Hospital

tspitzer@mgh.harvard.edu

6177241124

Study Officials

• Thomas R Spitzer, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Bone Marrow Transplant Program

Study Record Dates

• First Submitted: May 30, 2014
• First Posted: June 6, 2014
• Study Start: February 1, 2015
• Primary Completion: June 22, 2021
• Study Completion: June 22, 2021
• Last Updated: December 13, 2022
• Results First Posted: December 13, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)