NCT00801632

Brief Summary

In small initial studies, combined kidney and bone marrow transplants from the same donor have permitted some individuals to stop taking anti-rejection medicines without rejecting their transplant. This clinical trial will study this method in a greater number of people to determine if it is indeed effective and safe.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Dec 2008

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2008

Completed
1 day until next milestone

First Submitted

Initial submission to the registry

December 2, 2008

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 3, 2008

Completed
5.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2014

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2014

Completed
6 months until next milestone

Results Posted

Study results publicly available

May 12, 2015

Completed
Last Updated

November 10, 2015

Status Verified

November 1, 2015

Enrollment Period

5.3 years

First QC Date

December 2, 2008

Results QC Date

April 21, 2015

Last Update Submit

November 6, 2015

Conditions

Keywords

renal allograft tolerancemixed chimerismkidney transplantbone marrow transplantantirejectionimmunosuppression

Outcome Measures

Primary Outcomes (1)

  • Number of Participants Successfully Withdrawn Off of Immunosuppressant Medication for 104 Weeks

    A participant was considered a success if they were off immunosuppressive therapy for 104 consecutive weeks leading up to study week 208 (48 months post-transplant) or study termination, whichever occurred first.

    48 months post-transplant

Secondary Outcomes (7)

  • Percentage of Participants Experiencing Acute Rejection

    Transplantation until study completion or participant termination (up to five years)

  • Change in Renal Function

    Transplantation until study completion or participant termination (up to five years)

  • Percentage of Participants With Graft Survival Through 156 Weeks

    Transplantation until week 156

  • Percentage of Participants Surviving Through 156 Weeks

    Transplantation until week 156

  • Time to Neutrophil Recovery Following Transplant

    Transplantation until study completion or participant termination (participants followed up to five years)

  • +2 more secondary outcomes

Study Arms (1)

Kidney and Marrow Recipients

EXPERIMENTAL

Combined kidney and bone marrow transplant

Procedure: Kidney TransplantationProcedure: Bone marrow transplantationBiological: MEDI-507Drug: cyclophosphamideBiological: rituximabDrug: TacrolimusDrug: corticosteroidsRadiation: thymic irradiation

Interventions

Surgical transplantation of donor kidney

Also known as: Renal Transplantation
Kidney and Marrow Recipients

During kidney transplant, bone marrow cells donated by the same donor as the kidney are given through a plastic tube placed in a vein in the chest, underneath the collarbone

Kidney and Marrow Recipients
MEDI-507BIOLOGICAL

0.1 mg/kg on day -2; 0.6 mg/kg on days -1,0,1

Also known as: siplizumab, anti-CD2 monoclonal antibody
Kidney and Marrow Recipients

60 mg/kg infusion on days -5, -4

Also known as: Cytoxan
Kidney and Marrow Recipients
rituximabBIOLOGICAL

375 mg/m\^2 infusion on days -7, -2, 5, and 12

Also known as: Rituxan
Kidney and Marrow Recipients

0.05 mg/kg intravenously twice daily starting on day -1, adjusted to trough level of 10-15ng/ml, then tapered (if eligible) on days 1, 7, 14, 21, 28, 42, and 56

Also known as: PROGRAF®
Kidney and Marrow Recipients

2 mg/kg prednisone on day 4, with an additional 500-mg pulse of methylprednisolone given on days 10, 11, and 12, and then tapered off by day 20

Also known as: methylprednisolone, prednisone
Kidney and Marrow Recipients

700 cGy of thymic irradiation administered in a single dose on day -1

Kidney and Marrow Recipients

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Awaiting first or second transplant with a living donor or first transplant with a cadaveric donor
  • For living-donor transplants, must have one or more HLA antigen-mismatched donors identified
  • Serologic evidence of prior exposure to Epstein-Barr virus (EBV)

You may not qualify if:

  • ABO blood group-incompatibility for a kidney graft of tissue from a donor
  • Decreased circulating white blood cell count
  • Positive for HIV-1, hepatitis B and C viruses
  • Have had prior radiation therapy that could limit dose
  • Lung capacity \<50% of predicted normal
  • Evidence of insufficient cardiac capacity
  • Unwilling to use adequate contraception until 2 years after transplant
  • Lactation or pregnancy
  • Presence of antibody against the donor

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (2)

  • Kawai T, Cosimi AB, Spitzer TR, Tolkoff-Rubin N, Suthanthiran M, Saidman SL, Shaffer J, Preffer FI, Ding R, Sharma V, Fishman JA, Dey B, Ko DS, Hertl M, Goes NB, Wong W, Williams WW Jr, Colvin RB, Sykes M, Sachs DH. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008 Jan 24;358(4):353-61. doi: 10.1056/NEJMoa071074.

    PMID: 18216355BACKGROUND
  • Kawai T, Sachs DH, Sykes M, Cosimi AB; Immune Tolerance Network. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2013 May 9;368(19):1850-2. doi: 10.1056/NEJMc1213779. No abstract available.

Related Links

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Kidney TransplantationBone Marrow TransplantationsiplizumabCyclophosphamideRituximabTacrolimusAdrenal Cortex HormonesMethylprednisolonePrednisone

Condition Hierarchy (Ancestors)

Renal Insufficiency, ChronicRenal InsufficiencyKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Renal Replacement TherapyTherapeuticsOrgan TransplantationTransplantationSurgical Procedures, OperativeUrologic Surgical ProceduresUrogenital Surgical ProceduresTissue TransplantationCell- and Tissue-Based TherapyBiological TherapyPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsAntibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsMacrolidesLactonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsPrednisolonePregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsPregnadienediols

Results Point of Contact

Title
Director, Clinical Research Program
Organization
DAIT/NIAID

Study Officials

  • David Sachs, MD

    Massacusetts General Hospital

    PRINCIPAL INVESTIGATOR
  • Ben Cosimi, MD

    Massachusetts General Hospital

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 2, 2008

First Posted

December 3, 2008

Study Start

December 1, 2008

Primary Completion

April 1, 2014

Study Completion

November 1, 2014

Last Updated

November 10, 2015

Results First Posted

May 12, 2015

Record last verified: 2015-11

Locations