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

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Clinical Trial

Official title:

Low-Dose Total Body Irradiation and Fludarabine Followed By Unrelated Donor Stem Cell Transplantation for Patients With Fanconi Anemia - A Multicenter Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00093743
• Other study ID #: 1444.00
• Secondary ID: NCI-2012-0059314
• Status: Completed
• Phase: Phase 1
• First received: October 6, 2004
• Last updated: February 16, 2017
• Start date: January 2000

Study information

• Verified date: February 2017
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• 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)
• Anemia
• Childhood Acute Myeloid Leukemia in Remission
• Childhood Myelodysplastic Syndromes
• Fanconi Anemia
• Fanconi Syndrome
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Previously Treated Myelodysplastic Syndromes
• Syndrome

Intervention

Drug:
• fludarabine phosphate
Given IV
• cyclosporine
Given IV or PO

Radiation:
• total-body irradiation
Undergo TBI

Procedure:
• allogeneic bone marrow transplantation
Undergo allogeneic bone marrow transplantation
• allogeneic hematopoietic stem cell transplantation
Undergo allogeneic PBSC transplantation
• peripheral blood stem cell transplantation
Undergo allogeneic PBSC transplantation

Drug:
• mycophenolate mofetil
Given PO or IV

Locations

Country	Name	City	State
United States	Robert H. Lurie Comprehensive Cancer Center	Chicago	Illinois
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Regimen toxicity assessed using the Bearman scale	Patient data will be summarized using standard statistical methods.	Up to day 100
Primary	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