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

Primary Purpose

Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q)

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
fludarabine phosphate
cyclosporine
total-body irradiation
allogeneic bone marrow transplantation
allogeneic hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
mycophenolate mofetil
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Acute Myeloid Leukemia in Remission

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Robert H. Lurie Comprehensive Cancer Center
  • Riley Hospital for Children
  • Vanderbilt-Ingram Cancer Center
  • Huntsman Cancer Institute/University of Utah
  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (allogeneic bone marrow or PBSC transplantation)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
Regimen toxicity assessed using the Bearman scale
Patient data will be summarized using standard statistical methods.
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.

Secondary Outcome Measures

Full Information

First Posted
October 6, 2004
Last Updated
February 16, 2017
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00093743
Brief Title
Low-Dose Total-Body Irradiation and Fludarabine Phosphate Followed by Unrelated Donor Stem Cell Transplant in Treating Patients With Fanconi Anemia
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 Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
January 2000 (undefined)
Primary Completion Date
September 2007 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (allogeneic bone marrow or PBSC transplantation)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Other Intervention Name(s)
2-F-ara-AMP, Beneflur, Fludara
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Other Intervention Name(s)
ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune
Intervention Description
Given IV or PO
Intervention Type
Radiation
Intervention Name(s)
total-body irradiation
Other Intervention Name(s)
TBI
Intervention Description
Undergo TBI
Intervention Type
Procedure
Intervention Name(s)
allogeneic bone marrow transplantation
Other Intervention Name(s)
bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow
Intervention Description
Undergo allogeneic bone marrow transplantation
Intervention Type
Procedure
Intervention Name(s)
allogeneic hematopoietic stem cell transplantation
Intervention Description
Undergo allogeneic PBSC transplantation
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Other Intervention Name(s)
PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Intervention Description
Undergo allogeneic PBSC transplantation
Intervention Type
Drug
Intervention Name(s)
mycophenolate mofetil
Other Intervention Name(s)
Cellcept, MMF
Intervention Description
Given PO or IV
Primary Outcome Measure Information:
Title
Engraftment, defined as donor chimerism (mixed or complete)
Description
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.
Time Frame
Day 28
Title
Engraftment, defined as donor chimerism (mixed or complete)
Description
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.
Time Frame
Day 56
Title
Engraftment, defined as donor chimerism (mixed or complete)
Description
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.
Time Frame
Day 84
Title
Engraftment, defined as donor chimerism (mixed or complete)
Description
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.
Time Frame
Day 180
Title
Regimen toxicity assessed using the Bearman scale
Description
Patient data will be summarized using standard statistical methods.
Time Frame
Up to day 100
Title
Acute GvHD defined using the Seattle criteria
Description
For the evaluation of GvHD, time of onset, severity, and treatment will be recorded. Patient data will be summarized using standard statistical methods.
Time Frame
Day 84

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hans-Peter Kiem
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Robert H. Lurie Comprehensive Cancer Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Huntsman Cancer Institute/University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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