We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Low-Dose Total-Body Irradiation and Fludarabine Phosphate Followed by Unrelated Donor Stem Cell Transplant in Treating Patients With Fanconi Anemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00093743
Recruitment Status : Completed
First Posted : October 8, 2004
Last Update Posted : February 20, 2017
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Center

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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).

Condition or disease Intervention/treatment Phase
Adult Acute Myeloid Leukemia in Remission Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult 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 Remission Childhood Myelodysplastic Syndromes Fanconi Anemia Previously Treated Myelodysplastic Syndromes Drug: fludarabine phosphate Drug: cyclosporine Radiation: total-body irradiation Procedure: allogeneic bone marrow transplantation Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Drug: mycophenolate mofetil Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine whether donor chimerism can be achieved in patients with Fanconi anemia receiving marrow or peripheral blood stem cell (PBSC) grafts from unrelated donors following low dose total body irradiation (TBI), fludarabine (fludarabine phosphate), mycophenolate mofetil, and cyclosporine.

II. To determine the lowest dose of TBI necessary to achieve donor chimerism in at least 80% of patients.

III. To determine the incidence of severe regimen-related toxicity.

SECONDARY OBJECTIVES:

I. To determine the survival of Fanconi anemia patients transplanted with unrelated donor marrow or PBSC grafts after conditioning with a non-myeloablative regimen.

II. To determine the incidence and severity of graft-vs-host disease (GVHD) incurred with unrelated bone marrow or PBSC grafts transplant patients with Fanconi anemia.

III. To determine if mixed chimerism results in amelioration of symptoms associated with bone marrow failure in patients with Fanconi anemia.

OUTLINE:

NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (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 orally (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.

After completion of study treatment, patients are followed up at 6 months and annually thereafter.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Low-Dose Total Body Irradiation and Fludarabine Followed By Unrelated Donor Stem Cell Transplantation for Patients With Fanconi Anemia - A Multicenter Trial
Study Start Date : January 2000
Actual Primary Completion Date : September 2007

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Treatment (allogeneic bone marrow or PBSC transplantation)

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 phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara

Drug: cyclosporine
Given IV or PO
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune

Radiation: total-body irradiation
Undergo TBI
Other Name: TBI

Procedure: allogeneic bone marrow transplantation
Undergo allogeneic bone marrow transplantation
Other Names:
  • bone marrow therapy, allogeneic
  • bone marrow therapy, allogenic
  • transplantation, allogeneic bone marrow
  • transplantation, allogenic bone marrow

Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic PBSC transplantation

Procedure: peripheral blood stem cell transplantation
Undergo allogeneic PBSC transplantation
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell

Drug: mycophenolate mofetil
Given PO or IV
Other Names:
  • Cellcept
  • MMF


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Engraftment, defined as donor chimerism (mixed or complete) [ Time Frame: Day 28 ]
    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.

  2. Engraftment, defined as donor chimerism (mixed or complete) [ Time Frame: Day 56 ]
    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.

  3. Engraftment, defined as donor chimerism (mixed or complete) [ Time Frame: Day 84 ]
    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.

  4. Engraftment, defined as donor chimerism (mixed or complete) [ Time Frame: Day 180 ]
    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.

  5. Regimen toxicity assessed using the Bearman scale [ Time Frame: Up to day 100 ]
    Patient data will be summarized using standard statistical methods.

  6. Acute GvHD defined using the Seattle criteria [ Time Frame: Day 84 ]
    For the evaluation of GvHD, time of onset, severity, and treatment will be recorded. Patient data will be summarized using standard statistical methods.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00093743


Locations
Layout table for location information
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center
Chicago, Illinois, United States, 60611
United States, Indiana
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Utah
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States, 84112
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Center
National Heart, Lung, and Blood Institute (NHLBI)
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Hans-Peter Kiem Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Fred Hutchinson Cancer Center
ClinicalTrials.gov Identifier: NCT00093743    
Other Study ID Numbers: 1444.00
NCI-2012-00593 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
1444.00 ( Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
First Posted: October 8, 2004    Key Record Dates
Last Update Posted: February 20, 2017
Last Verified: February 2017
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Fanconi Syndrome
Anemia
Myelodysplastic Syndromes
Fanconi Anemia
Syndrome
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Hematologic Diseases
Bone Marrow Diseases
 Precancerous Conditions
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Congenital Bone Marrow Failure Syndromes
Bone Marrow Failure Disorders
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Male Urogenital Diseases