NCT00176878

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
10

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jun 2000

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

June 1, 2000

Completed
5.3 years until next milestone

First Submitted

Initial submission to the registry

September 12, 2005

Completed
3 days until next milestone

First Posted

Study publicly available on registry

September 15, 2005

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2009

Completed
5 months until next milestone

Results Posted

Study results publicly available

August 6, 2009

Completed
Last Updated

December 28, 2017

Status Verified

December 1, 2017

Enrollment Period

8.8 years

First QC Date

September 12, 2005

Results QC Date

June 18, 2009

Last Update Submit

December 3, 2017

Conditions

Keywords

Stem cell transplantT-cell depletionTLIbone marrow failure disorders

Outcome Measures

Primary Outcomes (1)

  • Number of Patients Alive (Survival) at 2 Years

    Calculated from day 1 of transplant to last contact.

    2 years

Secondary Outcomes (5)

  • Number of Patients Alive at Three Years (Survival)

    3 years

  • Number of Patients With Succcessful Engraftment After Transplantation

    42 Days

  • Number of Patients With Grade 2-4 Acute Graft Versus Host Disease

    100 Days

  • Number of Patients With Chronic Graft Versus Host Disease

    2 years

  • Number of Patients With Disease Recurrence

    2 years

Study Arms (1)

Bone Marrow Failure Disorders

EXPERIMENTAL

Patients with Diamond-Blackfan Anemia, Kostmann's Neutropenia, Shwachman-Diamond Syndrome

Procedure: Stem cell transplantDrug: Fludarabine monophosphateProcedure: Total lymphoid irradiationDrug: BusulfanBiological: anti-thymocyte globulin

Interventions

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.

Also known as: BMT
Bone Marrow Failure Disorders

fludarabine 175 mg/m\^2 (total) on Days -6 through -3.

Also known as: Fludara
Bone Marrow Failure Disorders

Dose 500 cGy radiation therapy to specific areas of the body

Also known as: TLI
Bone Marrow Failure Disorders

Busulfan 8 mg/kg (total) on Days - 8 and -7 (orally or through the catheter),

Also known as: Busulfex
Bone Marrow Failure Disorders

anti-thymocyte globulin (ATG) 15 mg/kg on days -2 and -1 via catheter

Also known as: ATG
Bone Marrow Failure Disorders

Eligibility Criteria

AgeUp to 35 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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).

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Anemia, Diamond-BlackfanShwachman-Diamond SyndromeBone Marrow Failure Disorders

Interventions

Stem Cell Transplantationfludarabine phosphateBusulfanAntilymphocyte Serum

Condition Hierarchy (Ancestors)

Anemia, Hypoplastic, CongenitalAnemia, AplasticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesRed-Cell Aplasia, PureCongenital Bone Marrow Failure SyndromesBone Marrow DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesExocrine Pancreatic InsufficiencyPancreatic DiseasesDigestive System DiseasesLipid Metabolism, Inborn ErrorsLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesLipomatosis

Intervention Hierarchy (Ancestors)

Cell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, OperativeButylene GlycolsGlycolsAlcoholsOrganic ChemicalsMesylatesAlkanesulfonatesAlkanesulfonic AcidsAlkanesHydrocarbons, AcyclicHydrocarbonsSulfonic AcidsSulfur AcidsSulfur CompoundsImmune SeraAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsBiological ProductsComplex Mixtures

Limitations and Caveats

Pharmacokinetic parameters in patients receiving 2 mg/kg/dose of busulfan twice daily was not performed. No data is available.

Results Point of Contact

Title
Paul Orchard, M.D.
Organization
Masonic Cancer Center, University of Minnesota

Study Officials

  • Paul Orchard, MD

    University of Minnesota Medical Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 12, 2005

First Posted

September 15, 2005

Study Start

June 1, 2000

Primary Completion

March 1, 2009

Study Completion

March 1, 2009

Last Updated

December 28, 2017

Results First Posted

August 6, 2009

Record last verified: 2017-12

Locations