Stem Cell Transplant for Bone Marrow Failure Syndromes

December 3, 2017 updated by: Masonic Cancer Center, University of Minnesota

Bone Marrow Transplantation for Non-Malignant Congenital Bone Marrow Failure Disorders

The researchers hypothesize that it will be possible to perform unrelated bone marrow or cord blood transplants in a safer manner by using less intensive therapy yet still achieve an acceptable level of donor cell engraftment for non-malignant congenital bone marrow failure disorders.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Prior to transplantation, subjects will receive the drugs busulfan (orally or through the catheter), as well as fludarabine and anti-thymocyte globulin (ATG) via the catheter. Busulfan, fludarabine and ATG will be given with Total Lymphoid Irradiation (TLI) to help the new donor bone marrow take and grow after transplantation.

Those patients receiving donor marrow will have the T cells (a type of white blood cell in the donor marrow) removed to lower the risk that the new marrow will react to their body, a condition called Graft-Versus-Host-Disease (GVHD). After bone marrow transplantation, subjects will receive drugs to help prevent GVHD, including cyclosporin and mycophenolate mofetil (MMF).

Blood samples are taken at day 28, day 60, day 100, 1 year and as required by medical status yearly for five years after transplant to evaluate how well the new marrow is growing. A bone marrow biopsy is required at day 21, at day 100 and 1 year.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 35 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients eligible for transplantation under this protocol will be <35 years of age, and will be diagnosed with:

    • a bone marrow failure syndrome unresponsive to available therapy, including but not limited to Diamond-Blackfan anemia, Shwachman Diamond syndrome or Kostmann's neutropenia but exclusive of aplastic anemia.

  • Diamond Blackfan Anemia:

    • Patients must show evidence of steroid resistance requiring equivalent of >6 transfusions yearly despite steroid therapy.
    • Evidence of developing aplasia or myelodysplasia will also be criteria for transplantation.

  • Kostmann's Neutropenia, Shwachman-Diamond syndrome:

    • Patients must have been previously diagnosed as having a clinical picture characteristic of Shwachman-Diamond syndrome (exocrine pancreatic insufficiency, growth retardation, metaphyseal dysostosis, neutropenia), or must have a bone marrow aspirate consistent with Kostmann's neutropenia, with no evidence of acute leukemia.
    • Patients must have failed therapy with granulocyte-colony stimulating factor (G-CSF), as determined by an inability to maintain an absolute neutrophil count (ANC) >750 cells/ml(3), or manifesting recurrent infections despite G-CSF administration resulting in life threatening infections or repeated hospitalizations (<4 /year).

Exclusion Criteria:

  • Patients >35 years of age
  • Karnofsky score <70%
  • Hepatic dysfunction as determined by bilirubin >3.0, ALT >150, or active hepatitis
  • Pulmonary function tests with forced volume vital capacity (FVC) and forced expiratory volume (FEV) <70%; O2 saturation <94%
  • Renal dysfunction with glomerular filtration rate (GFR) <30% of predicted.
  • Cardiac compromise, with left ejection fraction <45%.
  • Severe, stable neurologic impairment.
  • Human immunodeficiency virus (HIV) positivity.
  • Pregnant or lactating females

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Bone Marrow Failure Disorders
Patients with Diamond-Blackfan Anemia, Kostmann's Neutropenia, Shwachman-Diamond Syndrome
Procedure: Stem cell transplant
Stem cell transplant on Day 0 - healthy marrow from an unrelated individual. A minimum of 1.0 x 10^9/kg nucleated cells/kg ideal body weight will be collected with a goal of 2.0 x 10^9/kg.
Other Names:
  • BMT
Drug: Fludarabine monophosphate
fludarabine 175 mg/m^2 (total) on Days -6 through -3.
Other Names:
  • Fludara
Procedure: Total lymphoid irradiation
Dose 500 cGy radiation therapy to specific areas of the body
Other Names:
  • TLI
Drug: Busulfan
Busulfan 8 mg/kg (total) on Days - 8 and -7 (orally or through the catheter),
Other Names:
  • Busulfex
Biological: anti-thymocyte globulin
anti-thymocyte globulin (ATG) 15 mg/kg on days -2 and -1 via catheter
Other Names:
  • ATG

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients Alive (Survival) at 2 Years
Time Frame: 2 years
Calculated from day 1 of transplant to last contact.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients Alive at Three Years (Survival)
Time Frame: 3 years
Number of subjects who survived 3 years post-transplant.
3 years
Number of Patients With Succcessful Engraftment After Transplantation
Time Frame: 42 Days
Number of patients who received non-genotypic identical marrow or cord blood cells using a "non-myeloablative" preparative regimen and exhibited engraftment at Day 42.
42 Days
Number of Patients With Grade 2-4 Acute Graft Versus Host Disease
Time Frame: 100 Days
Number of patients with Grade 2, 3 and 4 Acute (normally observed within the first 100 days) Graft Versus Host Disease. Acute GVHD is staged as follows: overall grade (skin-liver-gut) with each organ staged individually from a low of 1 to a high of 4. Patients with grade IV GVHD usually have a poor prognosis. Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening.
100 Days
Number of Patients With Chronic Graft Versus Host Disease
Time Frame: 2 years
Number of patients who exhibited chronic (normally occurs after 100 days) Graft Versus Host Disease at 2 years post transplant. Chronic graft-versus-host-disease, over its long-term course, can also cause damage to the connective tissue and exocrine glands.
2 years
Number of Patients With Disease Recurrence
Time Frame: 2 years
Number of patients who exhibited disease recurrence at 2 years.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Masonic Cancer Center, University of Minnesota

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2000

Primary Completion (ACTUAL)

March 1, 2009

Study Completion (ACTUAL)

March 1, 2009

Study Registration Dates

First Submitted

September 12, 2005

First Submitted That Met QC Criteria

September 12, 2005

First Posted (ESTIMATE)

September 15, 2005

Study Record Updates

Last Update Posted (ACTUAL)

December 28, 2017

Last Update Submitted That Met QC Criteria

December 3, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MT2000-18
  • 9504M09637 (OTHER: IRB, University of Minnesota)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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