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

NCT ID: NCT00630253

Last Updated: 2021-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-02-17
• Study Completion Date: 2020-10-10

Brief 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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Marrow Isolex

bone marrow processed using Isolex 300i (for patients enrolled through April 2010)

Group Type: EXPERIMENTAL

Anti-Thymocyte Globulin

Intervention Type: BIOLOGICAL

30 mg/kg/day will be administered after MP on days -6, -5, -4, -3 and -2.

Cyclophosphamide

Intervention Type: DRUG

5 mg/kg is to be given as a 2 hour infusion, Days -6 through -3.

Fludarabine

Intervention Type: DRUG

35 mg/m\^2 intravenously (IV) on days -6 through -2.

Hematopoietic Stem Cell Transplantation

Intervention Type: PROCEDURE

Bone marrow or umbilical cord blood infusion on day 0.

Methylprednisolone

Intervention Type: DRUG

Methylprednisolone (MP) 2 mg/kg/day intravenously every 24 hours will be given from day -6 until day -2 as a premedication for ATG.

Filgrastim

Intervention Type: DRUG

5 mcg/kg per day intravenously (IV) continue until Absolute neutrophil count \> or = 2.5 x 10\^9/L

Cyclosporine

Intervention Type: DRUG

Cyclosporine IV over 2 hours or orally every 8-12 hours beginning on day -3 and continuing until day 100, followed by a taper.

Mycophenolate Mofetil

Intervention Type: DRUG

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).

UCB

No processing Notes: sibling donor UCB is used as the stem cell source and co-enroll for unlicensed UCB registry

Group Type: EXPERIMENTAL

Anti-Thymocyte Globulin

Intervention Type: BIOLOGICAL

30 mg/kg/day will be administered after MP on days -6, -5, -4, -3 and -2.

Cyclophosphamide

Intervention Type: DRUG

5 mg/kg is to be given as a 2 hour infusion, Days -6 through -3.

Fludarabine

Intervention Type: DRUG

35 mg/m\^2 intravenously (IV) on days -6 through -2.

Hematopoietic Stem Cell Transplantation

Intervention Type: PROCEDURE

Bone marrow or umbilical cord blood infusion on day 0.

Methylprednisolone

Intervention Type: DRUG

Methylprednisolone (MP) 2 mg/kg/day intravenously every 24 hours will be given from day -6 until day -2 as a premedication for ATG.

Filgrastim

Intervention Type: DRUG

5 mcg/kg per day intravenously (IV) continue until Absolute neutrophil count \> or = 2.5 x 10\^9/L

Cyclosporine

Intervention Type: DRUG

Cyclosporine IV over 2 hours or orally every 8-12 hours beginning on day -3 and continuing until day 100, followed by a taper.

Mycophenolate Mofetil

Intervention Type: DRUG

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).

Marrow Clinimax

bone marrow processed using CliniMACS (for patients enrolled beginning with the August 2010 protocol version)

Group Type: EXPERIMENTAL

Anti-Thymocyte Globulin

Intervention Type: BIOLOGICAL

30 mg/kg/day will be administered after MP on days -6, -5, -4, -3 and -2.

Cyclophosphamide

Intervention Type: DRUG

5 mg/kg is to be given as a 2 hour infusion, Days -6 through -3.

Fludarabine

Intervention Type: DRUG

35 mg/m\^2 intravenously (IV) on days -6 through -2.

Hematopoietic Stem Cell Transplantation

Intervention Type: PROCEDURE

Bone marrow or umbilical cord blood infusion on day 0.

Methylprednisolone

Intervention Type: DRUG

Methylprednisolone (MP) 2 mg/kg/day intravenously every 24 hours will be given from day -6 until day -2 as a premedication for ATG.

Filgrastim

Intervention Type: DRUG

5 mcg/kg per day intravenously (IV) continue until Absolute neutrophil count \> or = 2.5 x 10\^9/L

Cyclosporine

Intervention Type: DRUG

Cyclosporine IV over 2 hours or orally every 8-12 hours beginning on day -3 and continuing until day 100, followed by a taper.

Mycophenolate Mofetil

Intervention Type: DRUG

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).

Interventions

Anti-Thymocyte Globulin

30 mg/kg/day will be administered after MP on days -6, -5, -4, -3 and -2.

Intervention Type: BIOLOGICAL

Cyclophosphamide

5 mg/kg is to be given as a 2 hour infusion, Days -6 through -3.

Intervention Type: DRUG

Fludarabine

35 mg/m\^2 intravenously (IV) on days -6 through -2.

Intervention Type: DRUG

Hematopoietic Stem Cell Transplantation

Bone marrow or umbilical cord blood infusion on day 0.

Intervention Type: PROCEDURE

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.

Intervention Type: DRUG

Filgrastim

5 mcg/kg per day intravenously (IV) continue until Absolute neutrophil count \> or = 2.5 x 10\^9/L

Intervention Type: 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.

Intervention Type: 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).

Intervention Type: DRUG

Other Intervention Names

ATG; Cytoxan; Fludara; HSCT; MP; G-CSF; CSA; MMF

Eligibility 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.

• Maximum Eligible Age: 59 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Margaret L. MacMillan, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

0001M34441

Identifier Type: OTHER

Identifier Source: secondary_id

MT2000-09

Identifier Type: -

Identifier Source: org_study_id