NCT00093743

Brief Summary

Based on success in other diseases, the Fred Hutchinson Cancer Research Center (FHCRC) has developed a transplant procedure for Fanconi anemia (FA), which does not completely destroy the patient's remaining bone marrow. It should also be less harmful (toxic). Researchers wish to test whether this approach can overcome the graft failure often seen when bone marrow or peripheral blood stem cells from an unrelated donor are used. Researchers also will look at whether the procedure is less toxic than a conventional bone marrow transplant (BMT).

Trial Health

80
On Track

Trial Health Score

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

Enrollment
2

participants targeted

Target at below P25 for phase_1

Geographic Reach
1 country

5 active sites

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

January 1, 2000

Completed
4.8 years until next milestone

First Submitted

Initial submission to the registry

October 6, 2004

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 8, 2004

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2007

Completed
Last Updated

February 20, 2017

Status Verified

February 1, 2017

Enrollment Period

7.7 years

First QC Date

October 6, 2004

Last Update Submit

February 16, 2017

Conditions

Adult Acute Myeloid Leukemia in RemissionAdult Acute Myeloid Leukemia With 11q23 (MLL) AbnormalitiesAdult Acute Myeloid Leukemia With Del(5q)Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)Childhood Acute Myeloid Leukemia in RemissionChildhood Myelodysplastic SyndromesFanconi AnemiaPreviously Treated Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (6)

  • Engraftment, defined as donor chimerism (mixed or complete)

    Mixed chimerism is defined as presence of 5-95%, complete chimerism as \> 95% donor derived cells in the peripheral blood. Patient data will be summarized using standard statistical methods.

    Day 28

  • Engraftment, defined as donor chimerism (mixed or complete)

    Mixed chimerism is defined as presence of 5-95%, complete chimerism as \> 95% donor derived cells in the peripheral blood. Patient data will be summarized using standard statistical methods.

    Day 56

  • Engraftment, defined as donor chimerism (mixed or complete)

    Mixed chimerism is defined as presence of 5-95%, complete chimerism as \> 95% donor derived cells in the peripheral blood. Patient data will be summarized using standard statistical methods.

    Day 84

  • Engraftment, defined as donor chimerism (mixed or complete)

    Mixed chimerism is defined as presence of 5-95%, complete chimerism as \> 95% donor derived cells in the peripheral blood. Patient data will be summarized using standard statistical methods.

    Day 180

  • Regimen toxicity assessed using the Bearman scale

    Patient data will be summarized using standard statistical methods.

    Up to day 100

  • Acute GvHD defined using the Seattle criteria

    For the evaluation of GvHD, time of onset, severity, and treatment will be recorded. Patient data will be summarized using standard statistical methods.

    Day 84

Study Arms (1)

Treatment (allogeneic bone marrow or PBSC transplantation)

EXPERIMENTAL

NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2, cyclosporine IV every 8-12 hours on days -3 to 0, and undergo low-dose TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic bone marrow or PBSC transplantation on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO or IV every 8-12 hours on days 1-100 with taper to day 177, and mycophenolate mofetil PO or IV every 8 hours on days 0-40 with taper to day 96.

Drug: fludarabine phosphateDrug: cyclosporineRadiation: total-body irradiationProcedure: allogeneic bone marrow transplantationProcedure: allogeneic hematopoietic stem cell transplantationProcedure: peripheral blood stem cell transplantationDrug: mycophenolate mofetil

Interventions

fludarabine phosphateDRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara
Treatment (allogeneic bone marrow or PBSC transplantation)
cyclosporineDRUG

Given IV or PO

Also known as: ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune
Treatment (allogeneic bone marrow or PBSC transplantation)
total-body irradiationRADIATION

Undergo TBI

Also known as: TBI
Treatment (allogeneic bone marrow or PBSC transplantation)
allogeneic bone marrow transplantationPROCEDURE

Undergo allogeneic bone marrow transplantation

Also known as: bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow
Treatment (allogeneic bone marrow or PBSC transplantation)
allogeneic hematopoietic stem cell transplantationPROCEDURE

Undergo allogeneic PBSC transplantation

Treatment (allogeneic bone marrow or PBSC transplantation)
peripheral blood stem cell transplantationPROCEDURE

Undergo allogeneic PBSC transplantation

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Treatment (allogeneic bone marrow or PBSC transplantation)
mycophenolate mofetilDRUG

Given PO or IV

Also known as: Cellcept, MMF
Treatment (allogeneic bone marrow or PBSC transplantation)

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Any patient with marrow failure and increased chromosome fragility as determined in the diepoxybutane (DEB) or mitomycin C test
  • Any patient with Fanconi anemia (FA) with marrow failure meeting the following criteria:
  • Granulocyte count \< 0.2 x 10\^9/L
  • Platelet count \< 20 x 10\^9/L
  • Hemoglobin \< 8 g/dl
  • Corrected reticulocyte count \<1%
  • Any patient with FA as determined by DEB fragility, who has life-threatening marrow failure involving a single hematopoietic lineage
  • Any patient with FA and pre-existing cytogenetic abnormality including hematopoietic malignancy (myelodysplastic syndromes \[MDS\] or acute myeloid leukemia \[AML\]) in remission
  • DONOR: Unrelated Donors who are prospectively: Matched for human lymphocyte antigen (HLA)-DRB1 and DQB1 alleles (must be defined by high resolution typing); only a single allele disparity will be allowed for HLA -A, B, or C as defined by high resolution typing
  • DONOR: HLA typing will be performed at the highest level of resolution available at the time of transplant

You may not qualify if:

  • Evidence for hematopoietic malignancy in relapse
  • Heart or lung disease that would prevent compliance with conditioning and GvHD regimen or would severely limit the probability of survival
  • Human immunodeficiency virus (HIV) seropositive patients
  • Females who are pregnant or breastfeeding, or unwilling to use contraceptive techniques during and for the 12 months following treatment
  • DONOR: Donors who by DEB testing are found to have FA
  • DONOR: Donors who test positive in the lymphocytotoxic crossmatch assay
  • DONOR: Donors who are HIV positive
  • DONOR: Donors who for other medical or psychological reasons are not suitable as donors

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Congenital AbnormalitiesFanconi Anemia

Interventions

fludarabine phosphateCyclosporineWhole-Body IrradiationTransplantationPeripheral Blood Stem Cell TransplantationMycophenolic Acid

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and AbnormalitiesAnemia, Hypoplastic, CongenitalAnemia, AplasticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesCongenital Bone Marrow Failure SyndromesBone Marrow Failure DisordersBone Marrow DiseasesGenetic Diseases, InbornDNA Repair-Deficiency DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

CyclosporinsPeptides, CyclicMacrocyclic CompoundsPolycyclic CompoundsPeptidesAmino Acids, Peptides, and ProteinsRadiotherapyTherapeuticsInvestigative TechniquesSurgical Procedures, OperativeHematopoietic Stem Cell TransplantationStem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological TherapyCaproatesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsFatty AcidsLipids

Study Officials

  • Hans-Peter Kiem

    Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    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
SPONSOR

Study Record Dates

First Submitted

October 6, 2004

First Posted

October 8, 2004

Study Start

January 1, 2000

Primary Completion

September 1, 2007

Last Updated

February 20, 2017

Record last verified: 2017-02

Locations

US(5)