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
  Purpose

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.


Condition Intervention Phase
Fanconi Anemia
Biological: anti-thymocyte globulin
Drug: cyclophosphamide
Drug: fludarabine phosphate
Procedure: hematopoietic stem cell transplantation
Drug: methylprednisolone
Drug: filgrastim
Drug: cyclosporine
Drug: Mycophenolate Mofetil
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study of Cyclophosphamide, Fludarabine, and Antithymocyte Globulin Followed by Matched Sibling Donor Hematopoietic Cell Transplantation in Patients With Fanconi Anemia

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 45
Study Start Date: February 2000
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 59 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00630253

Contacts
Contact: Margaret MacMillan, M.D. 612-626-2778 macmi002@umn.edu

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Patricia Kleinke, RN    612-273-0857    Kleink1@fairview.org   
Principal Investigator: Margaret MacMillan, M.D.         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Margaret L. MacMillan, MD Masonic Cancer Center, University of Minnesota
  More Information

Additional Information:
No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00630253     History of Changes
Other Study ID Numbers: MT2000-09, 0001M34441
Study First Received: March 5, 2008
Last Updated: May 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
Fanconi anemia

Additional relevant MeSH terms:
Fanconi Anemia
Fanconi Syndrome
Anemia
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
Antilymphocyte Serum
Cyclophosphamide
Cyclosporins
Cyclosporine
Mycophenolate mofetil
Fludarabine monophosphate
Lenograstim
Fludarabine
Methylprednisolone Hemisuccinate
Prednisolone
Mycophenolic Acid
Vidarabine
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate

ClinicalTrials.gov processed this record on July 26, 2014