Cytoxan, Fludara, and Antithymocyte Globulin Conditioning Followed By Stem Cell Transplant in Treating Fanconi Anemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00630253
First received: March 5, 2008
Last updated: May 15, 2014
Last verified: May 2014

March 5, 2008
May 15, 2014
February 2000
August 2014   (final data collection date for primary outcome measure)
Graft failure [ Time Frame: From Day 1 to event ] [ Designated as safety issue: Yes ]
graft failure = absolute neutrophil count (ANC) <5 x 10^8/L and an acellular bone marrow aspirate/biopsy
  • Graft failure [ Designated as safety issue: No ]
  • Mortality at day 100 [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00630253 on ClinicalTrials.gov Archive Site
  • Incidence of Acute Graft-Versus-Host Disease (GVHD) [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
  • Overall survival [ Time Frame: 1 Year ] [ Designated as safety issue: No ]

    The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate.

    Overall survival will be defined as time from enrollment to date of death or censored at the date of last documented contact for patients still alive.

  • Incidence of Chronic Graft-Versus-Host Disease (GVHD) [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.
  • Transplant Related Deaths [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
    In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation
  • Incidence of acute graft-versus-host disease (GVHD) and chronic GVHD [ Designated as safety issue: Yes ]
  • Incidence of relapse [ Designated as safety issue: No ]
  • One-year survival [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Cytoxan, Fludara, and Antithymocyte Globulin Conditioning Followed By Stem Cell Transplant in Treating Fanconi Anemia
A Study of Cyclophosphamide, Fludarabine, and Antithymocyte Globulin Followed by Matched Sibling Donor Hematopoietic Cell Transplantation in Patients With Fanconi Anemia

RATIONALE: Giving chemotherapy, such as cyclophosphamide and fludarabine, before a donor stem cell transplant helps to remove the patient's cells to allow for the transplant cells to take and grow. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells can make an immune response against the body's normal cells. Giving antithymocyte globulin and removing the T cells from the donor cells before transplant and giving cyclosporine before and after transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the side effects of cyclophosphamide, fludarabine, and antithymocyte globulin followed by donor stem cell transplant and to see how well it works in treating patients with Fanconi anemia.

OBJECTIVES:

Primary

  • To determine the probability of engraftment in patients with Fanconi anemia treated with cyclophosphamide, fludarabine phosphate, and antithymocyte globulin followed by HLA-genotypically identical sibling donor hematopoietic stem cell transplantation that is T-cell depleted.

Secondary

  • To evaluate the incidence of acute graft-versus-host disease (GVHD) and chronic GVHD in patients treated with this regimen.
  • To evaluate the incidence of regimen-related toxicity in these patients.
  • To evaluate the 1-year survival of patients treated with this regimen.
  • To evaluate the incidence of late secondary malignancies (e.g., squamous cell carcinoma of the head and neck or cervix) in patients treated with this regimen.

OUTLINE:

  • Preparative cytoreductive therapy: Patients receive cyclophosphamide IV over 2 hours on days -6 to -3 and fludarabine phosphate IV over 30 minutes and anti-thymocyte globulin IV over 4-6 hours on days -6 to -2.
  • T-cell depleted donor hematopoietic stem cell transplantation: Patients undergo T-cell depleted donor bone marrow or umbilical cord blood stem cell transplantation on day 0. Patients also receive filgrastim (G-CSF) IV beginning on day 1 and continuing until blood counts recover.
  • Graft-versus-host disease prophylaxis: Patients receive cyclosporine IV over 2 hours or orally every 8-12 hours beginning on day -3 and continuing until day 100, followed by a taper. Patients will receive Mycophenolate Mofetil (MMF) therapy beginning on day -3 through day +30 or for 7 days after engraftment, whichever day is later, if no acute GVHD. Engraftment is defined as 1st day of 3 consecutive days of absolute neutrophil count [ANC] > 0.5 x 10^9/L.

After completion of study therapy, patients are followed periodically.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Fanconi Anemia
  • Biological: anti-thymocyte globulin
    30 mg/kg/day will be administered after MP on days -6, - 5, -4, -3 and -2.
    Other Name: ATGAM
  • Drug: cyclophosphamide
    5 mg/kg is to be given as a 2 hour infusion, Days -6 through -3.
    Other Name: Cytoxan
  • Drug: fludarabine phosphate
    35 mg/m^2 intravenously (IV) on days -6 through -2.
    Other Name: Fludara
  • Procedure: hematopoietic stem cell transplantation
    Bone marrow or umbilical cord blood infusion on day 0.
    Other Name: stem cell transplant
  • Drug: methylprednisolone
    MP 2 mg/kg/day intravenously every 24 hours will be given from day -6 until day +15 at which time it will be tapered 50% every 4 days to be discontinued by day +24 (i.e. MP 1 mg/kg/day on days +16-19, then 0.5 mg/kg/day on days +20-23, then discontinue). MP will be used as a premedication for ATG on day -6 to -2.
    Other Name: MP
  • Drug: filgrastim
    Initiate G-CSF 5 mcg/kg per day intravenously (IV) continue until Absolute neutrophil count > or = 2.5 x 10^9/L
    Other Name: G-CSF
  • Drug: cyclosporine
    cyclosporine IV over 2 hours or orally every 8-12 hours beginning on day -3 and continuing until day 100, followed by a taper
    Other Name: CSA
  • Drug: Mycophenolate Mofetil
    Patients will receive Mycophenolate Mofetil (MMF) therapy beginning on day -3 through day +30 or for 7 days after engraftment, whichever day is later, if no acute GVHD. Engraftment is defined as 1st day of 3 consecutive days of absolute neutrophil count [ANC] > 0.5 x 10^9/L. MMF will be given at a dose of 15 mg/kg/dose every 8 hours PO (to a maximum dose of 1 gram).
    Other Name: MMF
Experimental: Cyclophosphamide/Fludarabine/ATG
Patients with Fanconi Anemia receiving cyclophosphamide, fludarabine phosphate, antithymocyte globulin followed by matched sibling donor hematopoietic stem cell transplantation (HSCT). Patients also receive Mycophenolate Mofetil, methylprednisolone, cyclosporine and filgrastim.
Interventions:
  • Biological: anti-thymocyte globulin
  • Drug: cyclophosphamide
  • Drug: fludarabine phosphate
  • Procedure: hematopoietic stem cell transplantation
  • Drug: methylprednisolone
  • Drug: filgrastim
  • Drug: cyclosporine
  • Drug: Mycophenolate Mofetil
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
45
August 2014
August 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must be <60 years of age with a diagnosis of Fanconi Anemia (FA).
  • Patients must have an HLA-A, B, DRB1 identical sibling 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 moderately severe aplastic anemia (AA), early myelodysplastic syndrome (MDS) with no excess blasts with or without chromosomal abnormalities.

    • In patients <18 years of age, moderately severe aplastic anemia is defined as having at least one of the following:

      • platelet count <40 x 10^9/L
      • absolute neutrophil count (ANC) <10 x 10^8/L
      • Hgb <9 g/dL
    • In patients 18-60 years of age, moderately severe aplastic anemia is defined as having at least one of the following:

      • platelet count <20 x 10^9/L
      • absolute neutrophil count ANC <5 x 10^8/L
      • Hgb <8 g/dL
    • Early myelodysplastic syndrome, with multilineage dysplasia with < 5% blasts, with or without chromosomal anomalies.
  • Adequate major organ function including:

    • Cardiac: ejection fraction >45%
    • Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites)
    • 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:

  • Active bacterial infection within one week of hematopoietic cell transplant (HCT)
  • Active fungal infection at time of HCT.
  • Late MDS with greater than 5% blasts in bone marrow.
  • Acute myelogenous leukemia (AML) or history of AML
  • Malignant solid tumor (e.g. squamous cell carcinoma of the head/neck/cervix) within 2 years of HCT.
  • Pregnant or lactating female.
Both
up to 59 Years
No
Contact: Margaret MacMillan, M.D. 612-626-2778 macmi002@umn.edu
United States
 
NCT00630253
MT2000-09, 0001M34441
Yes
Masonic Cancer Center, University of Minnesota
Masonic Cancer Center, University of Minnesota
Not Provided
Principal Investigator: Margaret L. MacMillan, MD Masonic Cancer Center, University of Minnesota
Masonic Cancer Center, University of Minnesota
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP