Overview

This trial is active, not recruiting.

Conditions 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
Treatments fludarabine phosphate, cyclosporine, total-body irradiation, allogeneic bone marrow transplantation, allogeneic hematopoietic stem cell transplantation, peripheral blood stem cell transplantation, mycophenolate mofetil
Phase phase 1
Sponsor Fred Hutchinson Cancer Research Center
Collaborator National Heart, Lung, and Blood Institute (NHLBI)
Start date January 2000
End date September 2007
Trial size 2 participants
Trial identifier NCT00093743, 1444.00, NCI-2012-00593, P30CA015704

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).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(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.
fludarabine phosphate 2-F-ara-AMP
Given IV
cyclosporine ciclosporin
Given IV or PO
total-body irradiation TBI
Undergo TBI
allogeneic bone marrow transplantation bone marrow therapy, allogeneic
Undergo allogeneic bone marrow transplantation
allogeneic hematopoietic stem cell transplantation
Undergo allogeneic PBSC transplantation
peripheral blood stem cell transplantation PBPC transplantation
Undergo allogeneic PBSC transplantation
mycophenolate mofetil Cellcept
Given PO or IV

Primary Outcomes

Measure
Engraftment, defined as donor chimerism (mixed or complete)
time frame: Day 28
Engraftment, defined as donor chimerism (mixed or complete)
time frame: Day 56
Engraftment, defined as donor chimerism (mixed or complete)
time frame: Day 84
Engraftment, defined as donor chimerism (mixed or complete)
time frame: Day 180
Regimen toxicity assessed using the Bearman scale
time frame: Up to day 100
Acute GvHD defined using the Seattle criteria
time frame: Day 84

Eligibility Criteria

Male or female participants of any age.

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

Additional Information

Official title Low-Dose Total Body Irradiation and Fludarabine Followed By Unrelated Donor Stem Cell Transplantation for Patients With Fanconi Anemia - A Multicenter Trial
Principal investigator Hans-Peter Kiem
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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by Fred Hutchinson Cancer Research Center.