Cytoxan, Fludara, and Antithymocyte Globulin Conditioning Followed By Stem Cell Transplant in Treating Fanconi Anemia
Information source: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Fanconi Anemia
Intervention: anti-thymocyte globulin (Biological); cyclophosphamide (Drug); fludarabine phosphate (Drug); hematopoietic stem cell transplantation (Procedure); methylprednisolone (Drug); filgrastim (Drug); cyclosporine (Drug); Mycophenolate Mofetil (Drug)
Phase: Phase 1/Phase 2
Status: Recruiting
Sponsored by: Masonic Cancer Center, University of Minnesota Official(s) and/or principal investigator(s): Margaret L. MacMillan, MD, Principal Investigator, Affiliation: Masonic Cancer Center, University of Minnesota
Overall contact: Margaret MacMillan, M.D., Phone: 612-626-2778, Email: macmi002@umn.edu
Summary
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.
Clinical Details
Official title: A Study of Cyclophosphamide, Fludarabine, and Antithymocyte Globulin Followed by Matched Sibling Donor Hematopoietic Cell Transplantation in Patients With Fanconi Anemia
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Graft failure
Secondary outcome: Incidence of Acute Graft-Versus-Host Disease (GVHD)Overall survival Incidence of Chronic Graft-Versus-Host Disease (GVHD) Transplant Related Deaths
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
Minimum age: N/A.
Maximum age: 59 Years.
Gender(s): Both.
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.
Locations and Contacts
Margaret MacMillan, M.D., Phone: 612-626-2778, Email: macmi002@umn.edu
Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, United States; Recruiting Patricia Kleinke, RN, Phone: 612-273-0857, Email: Kleink1@fairview.org Margaret MacMillan, M.D., Principal Investigator
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: February 2000
Last updated: April 22, 2015
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