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

Primary Purpose

Fanconi Anemia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Anti-Thymocyte Globulin
Cyclophosphamide
Fludarabine
Hematopoietic Stem Cell Transplantation
Methylprednisolone
Filgrastim
Cyclosporine
Mycophenolate Mofetil
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fanconi Anemia focused on measuring Fanconi anemia

Eligibility Criteria

undefined - 59 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Masonic Cancer Center, University of Minnesota

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Marrow Isolex

UCB

Marrow Clinimax

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Number of Participants Experiencing Graft Failure
graft failure = absolute neutrophil count (ANC) <5 x 10^8/L and an acellular bone marrow aspirate/biopsy

Secondary Outcome Measures

Number of Participants With Acute Graft-Versus-Host Disease (GVHD)
Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Number of Participants Experiencing Overall Survival
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.
Number of Participants With Chronic Graft-Versus-Host Disease (GVHD)
Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.
Number of Participants With Transplant Related Deaths
In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation

Full Information

First Posted
March 5, 2008
Last Updated
October 8, 2021
Sponsor
Masonic Cancer Center, University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT00630253
Brief Title
Cytoxan, Fludara, and Antithymocyte Globulin Conditioning Followed By Stem Cell Transplant in Treating Fanconi Anemia
Official Title
A Study of Cyclophosphamide, Fludarabine, and Antithymocyte Globulin Followed by Matched Sibling Donor Hematopoietic Cell Transplantation in Patients With Fanconi Anemia
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
February 17, 2000 (Actual)
Primary Completion Date
October 10, 2020 (Actual)
Study Completion Date
October 10, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fanconi Anemia
Keywords
Fanconi anemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Marrow Isolex
Arm Type
Experimental
Arm Description
bone marrow processed using Isolex 300i (for patients enrolled through April 2010)
Arm Title
UCB
Arm Type
Experimental
Arm Description
No processing Notes: sibling donor UCB is used as the stem cell source and co-enroll for unlicensed UCB registry
Arm Title
Marrow Clinimax
Arm Type
Experimental
Arm Description
bone marrow processed using CliniMACS (for patients enrolled beginning with the August 2010 protocol version)
Intervention Type
Biological
Intervention Name(s)
Anti-Thymocyte Globulin
Other Intervention Name(s)
ATG
Intervention Description
30 mg/kg/day will be administered after MP on days -6, -5, -4, -3 and -2.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
5 mg/kg is to be given as a 2 hour infusion, Days -6 through -3.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
35 mg/m^2 intravenously (IV) on days -6 through -2.
Intervention Type
Procedure
Intervention Name(s)
Hematopoietic Stem Cell Transplantation
Other Intervention Name(s)
HSCT
Intervention Description
Bone marrow or umbilical cord blood infusion on day 0.
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone
Other Intervention Name(s)
MP
Intervention Description
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
Intervention Name(s)
Filgrastim
Other Intervention Name(s)
G-CSF
Intervention Description
5 mcg/kg per day intravenously (IV) continue until Absolute neutrophil count > or = 2.5 x 10^9/L
Intervention Type
Drug
Intervention Name(s)
Cyclosporine
Other Intervention Name(s)
CSA
Intervention Description
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
Intervention Name(s)
Mycophenolate Mofetil
Other Intervention Name(s)
MMF
Intervention Description
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).
Primary Outcome Measure Information:
Title
Number of Participants Experiencing Graft Failure
Description
graft failure = absolute neutrophil count (ANC) <5 x 10^8/L and an acellular bone marrow aspirate/biopsy
Time Frame
From Day 1 to event, assessed up to100 days
Secondary Outcome Measure Information:
Title
Number of Participants With Acute Graft-Versus-Host Disease (GVHD)
Description
Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Time Frame
Day 42
Title
Number of Participants Experiencing Overall Survival
Description
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.
Time Frame
1 Year
Title
Number of Participants With Chronic Graft-Versus-Host Disease (GVHD)
Description
Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.
Time Frame
1 Year
Title
Number of Participants With Transplant Related Deaths
Description
In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation
Time Frame
Day 100

10. Eligibility

Sex
All
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Margaret L. MacMillan, MD
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Masonic Cancer Center, University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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