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Hematopoietic Stem Cell Transplantation for Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using Total Body Irradiation, Cyclophosphamide and Fludarabine

Primary Purpose

Fanconi Anemia

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide
Fludarabine
Total body irradiation (TBI)
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fanconi Anemia focused on measuring Fanconi, Anemia, Stem Cell, Transplant

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Diagnosis:

  • Research participants must be have a diagnosis of Fanconi anemia (confirmed by mitomycin or diepoxybutane [DEB] chromosomal breakage testing).

Hematologic Diagnosis and Status:

  • Research participants must have one of the following hematologic diagnoses:

    • Severe Aplastic Anemia (SAA)/Severe Isolated Single lineage Cytopenia
    • Myelodysplastic Syndrome(MDS)
    • Acute leukemia.

HLA-compatible Unrelated volunteer donors:

  • Research participants who do not have a related HLA-matched donor but have an unrelated donor who is either matched at all A, B and DRB1 loci or who is mismatched at 1/6 loci (A, B, or DRB1) as tested by DNA analysis, will be eligible for entry on this protocol.

HLA-mismatched Related donors:

  • Research participants who do not have a related or unrelated HLA-compatible donor must have a healthy family member who is at least HLA-haplotype identical to the recipient. First degree related donors must have a normal DEB test.
  • The donor must be healthy and willing and able (1) to receive a 5 day course of G-CSF and undergo 2 daily leukaphereses, or (2) to undergo general anesthesia and bone marrow donation. In order to undergo a Tcell depletion, a donor should be able to have a volume of 15 ml/Kg of the research participant's body weight harvested safely.

HLA-compatible Cord Blood Units:

  • Research participants who do not have a related HLA-matched donor but have an unrelated placental cord blood unit which matched at all A, B and DRB1 loci or who is mismatched at 1/6 or 2/6 loci (A, B, or DRB1) as tested by DNA analysis, will be eligible for entry on this protocol.
  • Research participants may be of either gender or any ethnic background.
  • Research participants must have a Karnofsky adult, or Lansky pediatric performance scale status > 70%.
  • At the time of referral for transplantation, research participants must be in good clinical condition without co-existing medical problems that would significantly increase the risk of the transplant procedure. Research participants must be free of infections at the time of transplant. Research participants must have a life expectancy that is greater than 8 weeks.
  • Research participants must have adequate physical function measured by cardiac, Hepatic, Renal, Pulmonary.
  • Research participants must be available for follow-up evaluations at 30, 60, 180 days post BMT and yearly for 5 years.

Exclusion Criteria:

  • Active CNS leukemic involvement
  • Female research participants who are pregnant or breast-feeding
  • Active viral, bacterial or fungal infection
  • Research participant seropositive for HIV-I/II; HTLV -I/II

Sites / Locations

  • Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

This is an open-label single arm study of 131I-8H9, injected intravenously at 10 mCi/1.73 m^2 dose [intended specific activity of ~20 mCi/mg protein] preceded by administration of 50mg/1.73m^2 of unlabeled 8H9.

Outcomes

Primary Outcome Measures

Incidence & Quality of Engraftment & Hematopoietic Reconstitution
Number of patients who engrafted

Secondary Outcome Measures

Full Information

First Posted
January 7, 2008
Last Updated
June 29, 2016
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI), Miltenyi Biotec, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00595127
Brief Title
Hematopoietic Stem Cell Transplantation for Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using Total Body Irradiation, Cyclophosphamide and Fludarabine
Official Title
A Pilot Trial of Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using Total Body Irradiation, Cyclophosphamide and Fludarabine
Study Type
Interventional

2. Study Status

Record Verification Date
June 2016
Overall Recruitment Status
Completed
Study Start Date
June 2001 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
May 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI), Miltenyi Biotec, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this research study is to: (1) determine if the combination of low dose total body irradiation, low dose cyclophosphamide and the addition of fludarabine, and a serum to suppress the immune system can allow selected stem cells to take and grow; (2) determine if selected stem cells from the blood or marrow can take and not cause graft-versus-host disease (GvHD), and; (3) evaluate the side effects of the combination of low dose radiation and chemotherapy drugs used for these transplants.
Detailed Description
Patients with this disease are born with it and have a fragility of the genes (chromosomes) in all the cells of the body. The fragility of the chromosomes puts patients with FA at high risk for certain cancers. Patients with FA are especially at risk of having diseases of the blood and marrow systems. These include (1) aplastic anemia, a disease where there is a failure of the bone marrow to make blood cells and (2) myelodysplastic syndrome which is represented by a clone of cells of the marrow that becomes "malignant" and stops making adequate numbers of blood cells (it is also called preleukemia.) The progression of the myelodysplastic syndrome will lead to (3) acute leukemia. If you have Fanconi anemia and suffer from aplastic anemia, myelodysplastic syndrome, or leukemia standard treatment with medications or chemotherapy alone is not likely to cure these problems. An allogeneic blood or bone marrow (hematopoietic stem cell) transplant can be done to provide you with marrow or blood stem cells from a healthy donor that can develop a normal blood forming system. An allogeneic stem cell transplant can cure the problems of the marrow and blood system. It cannot cure the chromosome fragility of the whole body. When allogeneic stem cell transplants have been done for the treatment of FA using stem cells from donors other than matched siblings, they have been associated with a high risk of rejection of the transplant and of a complication called graft-versus-host disease. In order for the stem cells to grow and to kill leukemia cells, patients must receive chemotherapy and radiation therapy. This preparation is called cytoreduction. For patients with Fanconi anemia, the standard preparation for stem cell transplantation has been the use of total body irradiation (at a lower dose because of the high risk of side-effects) and a chemotherapy agent called cyclophosphamide (or Cytoxan) also at lower dose. While this has worked well with transplants from matched siblings, it was not enough in transplants from unrelated or cord blood donors and led to a high risk of rejection. In the last few years a medication called fludarabine was used successfully in transplants to give more immunosuppression and kill T-cells. Fludarabine allowed transplants to be done with low risks of rejection, and probably as importantly little risks of added side-effects. The addition of antithymocyte globulin to Total Body Irradiation, cyclophosphamide and fludarabine has made the chances of rejection very low.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
This is an open-label single arm study of 131I-8H9, injected intravenously at 10 mCi/1.73 m^2 dose [intended specific activity of ~20 mCi/mg protein] preceded by administration of 50mg/1.73m^2 of unlabeled 8H9.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide (10mg/kg/day x 4days)
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Fludarabine (30mg/m^2/day x 5 days)
Intervention Type
Radiation
Intervention Name(s)
Total body irradiation (TBI)
Intervention Description
TBI (450 cGY in a single fraction)
Primary Outcome Measure Information:
Title
Incidence & Quality of Engraftment & Hematopoietic Reconstitution
Description
Number of patients who engrafted
Time Frame
8 years

10. Eligibility

Sex
All
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Diagnosis: Research participants must be have a diagnosis of Fanconi anemia (confirmed by mitomycin or diepoxybutane [DEB] chromosomal breakage testing). Hematologic Diagnosis and Status: Research participants must have one of the following hematologic diagnoses: Severe Aplastic Anemia (SAA)/Severe Isolated Single lineage Cytopenia Myelodysplastic Syndrome(MDS) Acute leukemia. HLA-compatible Unrelated volunteer donors: Research participants who do not have a related HLA-matched donor but have an unrelated donor who is either matched at all A, B and DRB1 loci or who is mismatched at 1/6 loci (A, B, or DRB1) as tested by DNA analysis, will be eligible for entry on this protocol. HLA-mismatched Related donors: Research participants who do not have a related or unrelated HLA-compatible donor must have a healthy family member who is at least HLA-haplotype identical to the recipient. First degree related donors must have a normal DEB test. The donor must be healthy and willing and able (1) to receive a 5 day course of G-CSF and undergo 2 daily leukaphereses, or (2) to undergo general anesthesia and bone marrow donation. In order to undergo a Tcell depletion, a donor should be able to have a volume of 15 ml/Kg of the research participant's body weight harvested safely. HLA-compatible Cord Blood Units: Research participants who do not have a related HLA-matched donor but have an unrelated placental cord blood unit which matched at all A, B and DRB1 loci or who is mismatched at 1/6 or 2/6 loci (A, B, or DRB1) as tested by DNA analysis, will be eligible for entry on this protocol. Research participants may be of either gender or any ethnic background. Research participants must have a Karnofsky adult, or Lansky pediatric performance scale status > 70%. At the time of referral for transplantation, research participants must be in good clinical condition without co-existing medical problems that would significantly increase the risk of the transplant procedure. Research participants must be free of infections at the time of transplant. Research participants must have a life expectancy that is greater than 8 weeks. Research participants must have adequate physical function measured by cardiac, Hepatic, Renal, Pulmonary. Research participants must be available for follow-up evaluations at 30, 60, 180 days post BMT and yearly for 5 years. Exclusion Criteria: Active CNS leukemic involvement Female research participants who are pregnant or breast-feeding Active viral, bacterial or fungal infection Research participant seropositive for HIV-I/II; HTLV -I/II
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Farid Boulad, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mskcc.org
Description
Memorial Sloan-Kettering Cancer Center

Learn more about this trial

Hematopoietic Stem Cell Transplantation for Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using Total Body Irradiation, Cyclophosphamide and Fludarabine

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