Stem Cell Transplantation for Fanconi Anemia - Full Text View

Purpose

The purpose of this study is to determine whether thymic shielding during total body irradiation can be given and whether it will reduce the risk of infections in Fanconi Anemia patients undergoing alternate donor (not a matched sibling) stem cell transplants.

Condition	Intervention	Phase
Fanconi Anemia	Procedure: Hematopoietic Stem Cell Transplant Procedure: Thymic Shielding During Radiation Procedure: Total Body Irradiation Drug: Cyclophosphamide, Fludarabine	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Study of Thymic Shielding in Recipients of Total Body Irradiation, Cyclophosphamide, and Fludarabine Followed by Alternate Donor Hematopoietic Stem Cell Transplantation in Patients With Fanconi Anemia

Resource links provided by NLM:

Genetics Home Reference related topics: Fanconi anemia

MedlinePlus related topics: Anemia

Drug Information available for: Cyclophosphamide Fludarabine Fludarabine phosphate

U.S. FDA Resources

Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:

Number of Patients Who Exhibited Hematopoietic Recovery and Engraftment [ Time Frame: Day 42 after hematopoietic cell transplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Number of Patients Who Exhibited Secondary Graft Failure [ Time Frame: Day 100 after hematopoietic cell transplant ] [ Designated as safety issue: No ]
Number of Patients With Acute Graft Versus-Host Disease (aGVHD) [ Time Frame: Day 100 after hematopoietic cell transplant ] [ Designated as safety issue: Yes ]
Number of Patients With Chronic Graft Versus-Host Disease (GVHD) [ Time Frame: 1 year after hematopoietic cell transplant ] [ Designated as safety issue: Yes ]
Number of Patients Who Exhibited Regimen-related Toxicity (RRT) [ Time Frame: 1 year after hematopoietic cell transplant ] [ Designated as safety issue: Yes ]
Immune Reconstitution - Mean Value (1 Year) [ Time Frame: 1 year post-transplant. ] [ Designated as safety issue: No ]
Immune Reconstitution - Mean Value (2 Years) [ Time Frame: at 2 years after transplant ] [ Designated as safety issue: No ]
Number of Patients Alive at 1 Year [ Time Frame: 1 year after transplant ] [ Designated as safety issue: No ]
Number of Patients Alive at 2 Years [ Time Frame: 2 years after transplant ] [ Designated as safety issue: No ]

Enrollment:	16
Study Start Date:	March 2004
Study Completion Date:	December 2008
Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: HSCT Patients Patients who received total body irradiation (450 cGy [centigray]) with thymic shielding prior to chemotherapy regimen and Hematopoietic Stem Cell Transplant (HSCT)	Procedure: Hematopoietic Stem Cell Transplant Bone marrow failure may be treated by giving patients stem cells that come from someone else. This is called a stem-cell transplant. As part of the transplant process, patients receive high doses of chemotherapy and/or radiation to treat their underlying disease. As one of its effects, this treatment also kills the healthy stem cells that are already in the marrow. The transplant provides new stem cells for the patient from a healthy donor; that replace the bone marrow and allow the blood counts to recover. Other Name: Bone Marrow Transplant Procedure: Thymic Shielding During Radiation protecting the thymus during total body radiation (450 cGy administered) Other Name: TBI Procedure: Total Body Irradiation Six days before the stem cells are given (day -6), subjects will receive total body irradiation with thymic shielding. Thymic shielding is done by placing a piece of lead on the chest during the irradiation treatment so that the irradiation beams do not go to the thymus. Other Name: Radiation Therapy, Therapuetic Radiation Drug: Cyclophosphamide, Fludarabine Day -5 through Day -2, subjects will receive a chemotherapy regimen of Fludarabine, Cyclophosphamide via central line Other Name: Cytoxan, Fludara

Arms

Assigned Interventions

Experimental: HSCT Patients

Patients who received total body irradiation (450 cGy [centigray]) with thymic shielding prior to chemotherapy regimen and Hematopoietic Stem Cell Transplant (HSCT)

Procedure: Hematopoietic Stem Cell Transplant

Bone marrow failure may be treated by giving patients stem cells that come from someone else. This is called a stem-cell transplant. As part of the transplant process, patients receive high doses of chemotherapy and/or radiation to treat their underlying disease. As one of its effects, this treatment also kills the healthy stem cells that are already in the marrow. The transplant provides new stem cells for the patient from a healthy donor; that replace the bone marrow and allow the blood counts to recover.

Other Name: Bone Marrow Transplant

Procedure: Thymic Shielding During Radiation

protecting the thymus during total body radiation (450 cGy administered)

Other Name: TBI

Procedure: Total Body Irradiation

Six days before the stem cells are given (day -6), subjects will receive total body irradiation with thymic shielding. Thymic shielding is done by placing a piece of lead on the chest during the irradiation treatment so that the irradiation beams do not go to the thymus.

Other Name: Radiation Therapy, Therapuetic Radiation

Drug: Cyclophosphamide, Fludarabine

Day -5 through Day -2, subjects will receive a chemotherapy regimen of Fludarabine, Cyclophosphamide via central line

Other Name: Cytoxan, Fludara

Detailed Description:

All subjects will be given the same treatment regimen of total body irradiation (TBI), Fludarabine, Cyclophosphamide, and anti-thymocyte globulin (ATG), followed by an alternate donor stem cell transplant. Since this treatment regimen has been given before, without thymic shielding, we will compare the outcomes of these patients with the historical data from subjects who did not receive thymic shielding.

Eligibility

Ages Eligible for Study:	up to 18 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients must be less than (<) 18 years of age with a diagnosis of Fanconi anemia.
Patients must have an HLA-A, B, DRB1 identical unrelated donor or less than or equal to (≤)1 antigen mismatched related (non-HLA-matched sibling) or <1 antigen mismatched unrelated UCB donor. Patients and donors will be typed for HLA-A and B using serological or molecular techniques and for DRB1 using high resolution molecular typing.
Patients with FA must have aplastic anemia (AA), myelodysplastic syndrome without excess blasts, or high risk genotype as defined below.
- Aplastic anemia is defined as having at least one of the following when not receiving growth factors or transfusions
- Platelet count <20 x 10^9/L
- ANC <5 x 10^8/L
- Hgb <8 g/dL
- Myelodysplastic syndrome with multilineage dysplasia with or without chromosomal anomalies
- High risk genotype (e.g. IVS-4 or exon 14 FANCC mutations, or BRCA1 or 2 mutations)
Adequate major organ function including
- Cardiac: ejection fraction greater than (>)45%
- Hepatic: bilirubin, AST/ALT, ALP <2 x normal
- Karnofsky performance status >70% or Lansky performance status >50%
Women of child-bearing age must be using adequate birth control and have a negative pregnancy test

Exclusion Criteria:

Available HLA-genotypically identical related donor
History of gram negative sepsis or systemic fungal infection (proven or suspected based on radiographic studies)
Refractory anemia with excess blasts, or leukemia
Active central nervous system (CNS) leukemia at time of hematopoietic cell transplant (HCT)
History of squamous cell carcinoma of the head/neck/cervix within 2 years of HCT
Pregnant or lactating female
Prior radiation therapy preventing use of total body irradiation (TBI) 450 centigray (cGy)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00167206

Locations

United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

Investigators

Principal Investigator:

Margaret MacMillan, MD

Masonic Cancer Center, University of Minnesota

More Information

No publications provided

Responsible Party:	MacMillan, Margaret L., MD, Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:	NCT00167206 History of Changes
Other Study ID Numbers:	0312M54991, MT2003-18
Study First Received:	September 9, 2005
Results First Received:	July 7, 2009
Last Updated:	November 30, 2009
Health Authority:	United States: Institutional Review Board

Keywords provided by Masonic Cancer Center, University of Minnesota:

Stem Cell Transplant
Thymic Shielding
Total Body Irradiation
Chemotherapy

Additional relevant MeSH terms:

Anemia
Fanconi Anemia
Fanconi Syndrome
Hematologic Diseases
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Bone Marrow Diseases
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases
Kidney Diseases
Urologic Diseases
Renal Tubular Transport, Inborn Errors
Metabolism, Inborn Errors
Cyclophosphamide

Fludarabine monophosphate
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on June 13, 2013