Stem Cell Transplantation for Fanconi Anemia

NCT00167206 | Terminated Phase 1 Results DMC

• 2 other identifiers: 0312M54991MT2003-18
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Fanconi Anemia

Keywords

Stem Cell Transplant; Thymic Shielding; Total Body Irradiation; Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Number of Patients Who Exhibited Hematopoietic Recovery and Engraftment

  Calculated from Day 1 of hematopoietic cell transplant to Day 42 post-transplant. Hematopoietic recovery and engraftment is defined as the first of three consecutive days the patient's absolute neutrophil count is greater than or equal to 0.5X10\^9/Liter.

  Day 42 after hematopoietic cell transplant

Secondary Outcomes (8)

• Number of Patients Who Exhibited Secondary Graft Failure

  Day 100 after hematopoietic cell transplant

• Number of Patients With Acute Graft Versus-Host Disease (aGVHD)

  Day 100 after hematopoietic cell transplant

• Number of Patients With Chronic Graft Versus-Host Disease (GVHD)

  1 year after hematopoietic cell transplant

• Number of Patients Who Exhibited Regimen-related Toxicity (RRT)

  1 year after hematopoietic cell transplant

• Immune Reconstitution - Mean Value (1 Year)

  1 year post-transplant.

Study Arms (1)

HSCT Patients

EXPERIMENTAL

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; Procedure: Thymic Shielding During Radiation; Procedure: Total Body Irradiation; Drug: Cyclophosphamide, Fludarabine

Interventions

Hematopoietic Stem Cell Transplant 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.

Also known as: Bone Marrow Transplant

HSCT Patients

Thymic Shielding During Radiation PROCEDURE

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

Also known as: TBI

HSCT Patients

Total Body Irradiation 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.

Also known as: Radiation Therapy, Therapuetic Radiation

HSCT Patients

Cyclophosphamide, Fludarabine DRUG

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

Also known as: Cytoxan, Fludara

HSCT Patients

Eligibility Criteria

• Age: 1 Day - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (1)

• 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.

  PMID: 25824692 DERIVED

MeSH Terms

Conditions

Fanconi Anemia

Interventions

Stem Cell Transplantation; Bone Marrow Transplantation; Whole-Body Irradiation; Radiotherapy; CF regimen; Cyclophosphamide; fludarabine phosphate

Condition Hierarchy (Ancestors)

Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Tissue Transplantation; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Limitations and Caveats

Study ended early as thymic shielding was found to be safe. Therefore, a new study was designed using thymic shielding.

Results Point of Contact

• Title: Margaret MacMillan, M.D.
• Organization: Masonic Cancer Center, University of Minnesota

macmi002@umn.edu

612-626-2778

Study Officials

• Margaret MacMillan, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2005
• First Posted: September 14, 2005
• Study Start: March 1, 2004
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: August 26, 2019
• Results First Posted: November 26, 2009

Record last verified: 2019-08

Locations

US (1)