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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00093743
First received: October 6, 2004
Last updated: March 10, 2014
Last verified: March 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Engraftment, defined as donor chimerism (mixed or complete) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    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.

  • Engraftment, defined as donor chimerism (mixed or complete) [ Time Frame: Day 56 ] [ Designated as safety issue: No ]
    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.

  • Engraftment, defined as donor chimerism (mixed or complete) [ Time Frame: Day 84 ] [ Designated as safety issue: No ]
    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.

  • Engraftment, defined as donor chimerism (mixed or complete) [ Time Frame: Day 180 ] [ Designated as safety issue: No ]
    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.

  • Regimen toxicity assessed using the Bearman scale [ Time Frame: Up to day 100 ] [ Designated as safety issue: Yes ]
    Patient data will be summarized using standard statistical methods.

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


Enrollment: 2
Study Start Date: January 2000
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00093743

Locations
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 Research Center
Investigators
Principal Investigator: Hans-Peter Kiem Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00093743     History of Changes
Other Study ID Numbers: 1444.00, NCI-2012-00593, 1444.00, P30CA015704
Study First Received: October 6, 2004
Last Updated: March 10, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Anemia
Myelodysplastic Syndromes
Preleukemia
Leukemia
Syndrome
Fanconi Anemia
Fanconi Syndrome
Neoplasms by Histologic Type
Neoplasms
Hematologic Diseases
Bone Marrow Diseases
Precancerous Conditions
Disease
Pathologic Processes
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases
Kidney Diseases
Urologic Diseases
Renal Tubular Transport, Inborn Errors
Metabolism, Inborn Errors
Fludarabine
Fludarabine phosphate
Mycophenolic Acid
Cyclosporins
Cyclosporine

ClinicalTrials.gov processed this record on October 01, 2014