Stem Cell Transplantation for Fanconi Anemia

NCT ID: NCT00167206

Last Updated: 2019-08-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-03-31
• Study Completion Date: 2008-12-31

Brief Summary

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.

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.

Conditions

Fanconi Anemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HSCT Patients

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

Group Type: EXPERIMENTAL

Hematopoietic Stem Cell Transplant

Intervention Type: PROCEDURE

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.

Thymic Shielding During Radiation

Intervention Type: PROCEDURE

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

Total Body Irradiation

Intervention Type: PROCEDURE

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.

Cyclophosphamide, Fludarabine

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: PROCEDURE

Thymic Shielding During Radiation

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

Intervention Type: 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.

Intervention Type: PROCEDURE

Cyclophosphamide, Fludarabine

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

Intervention Type: DRUG

Other Intervention Names

Bone Marrow Transplant; TBI; Radiation Therapy, Therapuetic Radiation; Cytoxan, Fludara

Eligibility 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)

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Margaret MacMillan, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

References

MacMillan ML, DeFor TE, Young JA, Dusenbery KE, Blazar BR, Slungaard A, Zierhut H, Weisdorf DJ, Wagner JE. Alternative donor hematopoietic cell transplantation for Fanconi anemia. Blood. 2015 Jun 11;125(24):3798-804. doi: 10.1182/blood-2015-02-626002. Epub 2015 Mar 30.

Reference Type: DERIVED

PMID: 25824692 (View on PubMed)

Other Identifiers

MT2003-18

Identifier Type: OTHER

Identifier Source: secondary_id

0312M54991

Identifier Type: -

Identifier Source: org_study_id