TBI Dose De-escalation for Fanconi Anemia - Full Text View

Sponsor:	Masonic Cancer Center, University of Minnesota
Information provided by:	Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:	NCT00352976

Purpose

This is a single arm, total body irradiation (TBI) trial. All patients will be prescribed TBI 300 cGy with the goal of evaluating secondary endpoints.

Condition	Intervention	Phase
Fanconi Anemia	Drug: Cyclophosphamide Drug: Fludarabine Drug: anti-thymocyte globulin (ATG) Procedure: Total Body Irradiation Procedure: Bone Marrow Transplantation	Phase II Phase III

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Crossover Assignment, Safety/Efficacy Study
Official Title:	Total Body Irradiation Dose De-escalation Study in Patients With Fanconi Anemia Undergoing Alternate Donor Hematopoietic Cell Transplantation

Resource links provided by NLM:

MedlinePlus related topics: Anemia Bone Marrow Transplantation

Drug Information available for: Cyclophosphamide Fludarabine Fludarabine monophosphate

U.S. FDA Resources

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

Primary Outcome Measures:

Incidence of neutrophil recovery (absolute neutrophil count ≥500/µL for three consecutive days) . [ Time Frame: by day 42 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Incidence of grade ≥3 regimen related toxicity . [ Time Frame: at day 100 ] [ Designated as safety issue: Yes ]
Incidence of secondary graft failure at 100 days. [ Time Frame: 100 days ] [ Designated as safety issue: No ]
Incidence of acute graft-versus-host disease (GVHD) [ Time Frame: at 100 days. ] [ Designated as safety issue: No ]
Incidence of chronic GVHD . [ Time Frame: at one year ] [ Designated as safety issue: No ]
Probability of survival . [ Time Frame: at one year ] [ Designated as safety issue: No ]
Incidence of infections . [ Time Frame: at 100 days, 6 months and one year ] [ Designated as safety issue: No ]
Immune reconstitution . [ Time Frame: at 100 days, 6 month and one year ] [ Designated as safety issue: No ]

Estimated Enrollment:	45
Study Start Date:	May 2006
Estimated Study Completion Date:	May 2016
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Treatment with TBI: Experimental Patients treated with total body irradiation, chemotherapy and transplant.	Drug: Cyclophosphamide Day -5 through Day -2, subjects will receive chemotherapy of Cyclophosphamide via central line (i.e. Hickman or Broviac). Drug: Fludarabine Day -5 through Day -2, subjects will receive chemotherapy of Fludarabine via central line (i.e. Hickman or Broviac). Drug: anti-thymocyte globulin (ATG) Day -5 through Day -2, subjects will receive chemotherapy of ATG via central line (i.e. Hickman or Broviac). Procedure: Total Body Irradiation total body irradiation with thymic shielding will be given six days before the stem cells are given (day -6). 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. Procedure: Bone Marrow Transplantation Certain cancers can 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, such as cancer. 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.

Arms

Assigned Interventions

Treatment with TBI: Experimental

Patients treated with total body irradiation, chemotherapy and transplant.

Drug: Cyclophosphamide

Day -5 through Day -2, subjects will receive chemotherapy of Cyclophosphamide via central line (i.e. Hickman or Broviac).

Drug: Fludarabine

Day -5 through Day -2, subjects will receive chemotherapy of Fludarabine via central line (i.e. Hickman or Broviac).

Drug: anti-thymocyte globulin (ATG)

Day -5 through Day -2, subjects will receive chemotherapy of ATG via central line (i.e. Hickman or Broviac).

Procedure: Total Body Irradiation

total body irradiation with thymic shielding will be given six days before the stem cells are given (day -6). 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.

Procedure: Bone Marrow Transplantation

Certain cancers can 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, such as cancer. 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.

Detailed Description:

Study Treatment: 1. If the subject is to receive total body irradiation with thymic shielding, it will be given six days before the stem cells are given (day -6). 2. Day -5 through Day -2, subjects will receive a chemotherapy regimen of Fludarabine, Cyclophosphamide, anti-thymocyte globulin (ATG), and Methylprednisone (a steroid used to help make sure the transplant "takes") via central line (i.e. Hickman or Broviac). On days -5 to -1, subjects will receive ATG and Methylprednisone. The methylprednisone will continue until about three weeks after transplant.3. Starting Day -3, subjects will be given cyclosporin A (CSA) therapy to help prevent graft-versus-host-disease. We will continue to give CSA until about six months after the transplant. 4. If the subject is receiving bone marrow or "peripheral" stem cells (cells collected from the donor's arm via a cell separator), on the day of transplantation, the stem cells taken from the donor will be put into a machine which will separate the lymphocytes (the cells that cause graft-versus-host disease [GVHD]) from the stem cells. If the subject is receiving an umbilical cord blood, the lymphocytes will not be removed because the risk of GVHD is not as high. Otherwise all patients will receive the same treatment. The stem cells are given as an infusion into the subject's existing catheter over 1-2 hours on day 0.5. On the day after transplant (day +1) subjects will be given G-CSF to stimulate the growth of the transplanted cells. 6. While receiving treatment and until the subject's blood counts recover he/she will have daily blood tests, and several bone marrow biopsies and aspirates. After recovery, subjects will be seen once a month for a health assessment and blood tests until at least 3 months after the cells have been infused. Additional blood tests or assessments may be done as medically indicated.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Standard risk patients must be <18 years of age with a diagnosis of Fanconi anemia (FA)with 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
absolute neutrophil count (ANC) <5 x 10^8/L
hemoglobin (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)
High risk FA patients must have at least one of the following:
- History at any time of systemic fungal or gram negative infection
- Severe renal disease with a creatinine clearance <40 mL/min
- Recipient age > or = 18 years
- Advanced myelodysplastic syndrome (MDS) (i.e., RAEB or RAEBt) or acute leukemia
Patients must have a ≤1 antigen mismatched HLA-A, B, DRB1 unrelated donor or ≤1 antigen mismatched related (non-HLA-matched sibling) or ≤2 antigen mismatched unrelated UCB donor.
Adequate major organ function including: cardiac - ejection fraction >45%, hepatic - bilirubin, AST/ALT, ALP <5x normal, Karnofsky performance status >70% or Lansky >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.
Refractory anemia with excess blasts, or leukemia.
Active CNS leukemia at time of hematopoietic stem cell transplant(HSCT).
History of squamous cell carcinoma of the head/neck/cervix within 2 years of HSCT.
Pregnant or lactating female.
Prior radiation therapy that prevents further total body irradiation (TBI).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00352976

Contacts

Contact: Margaret L MacMillan, M.D.

612-626-2778

macmi002@umn.edu

Locations

United States, Minnesota
University of Minnesota Medical Center	Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Margaret L MacMillan, M.D. 612-626-2778 macmi002@umn.edu

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

Investigators

Principal Investigator:

Margaret L MacMillan, M.D.

University of Minnesota Medical Center

More Information

No publications provided

Responsible Party:	Masonic Cancer Center, University of Minnesota ( MacMillan, Margaret L., MD )
Study ID Numbers:	0605M85788, MT2006-05
Study First Received:	July 14, 2006
Last Updated:	October 1, 2009
ClinicalTrials.gov Identifier:	NCT00352976 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Masonic Cancer Center, University of Minnesota:

Bone Marrow transplant
stem cell transplant
cord blood transplant
total body irradiation
thymic shielding

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
DNA Repair-Deficiency Disorders
Physiological Effects of Drugs
Cyclophosphamide
Therapeutic Uses
Anemia, Aplastic
Alkylating Agents
Metabolic Diseases
Hematologic Diseases

Fanconi Anemia
Anemia
Fludarabine monophosphate
Immunosuppressive Agents
Pharmacologic Actions
Antilymphocyte Serum
Anemia, Hypoplastic, Congenital
Genetic Diseases, Inborn
Myeloablative Agonists
Fludarabine
Antineoplastic Agents, Alkylating
Bone Marrow Diseases
Antirheumatic Agents

ClinicalTrials.gov processed this record on November 25, 2009