NCT00630253

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

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 31 (actual)
• Sponsor: Masonic Cancer Center, University of Minnesota · Academic / Other
• Sex: All
• Age: 59 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Fanconi Anemia

Interventions

Type	Name	Description
BIOLOGICAL	Anti-Thymocyte Globulin	30 mg/kg/day will be administered after MP on days -6, -5, -4, -3 and -2.
DRUG	Cyclophosphamide	5 mg/kg is to be given as a 2 hour infusion, Days -6 through -3.
DRUG	Fludarabine	35 mg/m\^2 intravenously (IV) on days -6 through -2.
PROCEDURE	Hematopoietic Stem Cell Transplantation	Bone marrow or umbilical cord blood infusion on day 0.
DRUG	Methylprednisolone	Methylprednisolone (MP) 2 mg/kg/day intravenously every 24 hours will be given from day -6 until day -2 as a premedication for ATG.
DRUG	Filgrastim	5 mcg/kg per day intravenously (IV) continue until Absolute neutrophil count \> or = 2.5 x 10\^9/L
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.
DRUG	Mycophenolate Mofetil	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).

Timeline

• Start date: 2000-02-17
• Primary completion: 2020-10-10
• Completion: 2020-10-10
• First posted: 2008-03-06
• Last updated: 2021-10-12
• Results posted: 2021-10-12

Locations

1 site across 1 country: United States