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

June 29, 2016 updated by: Memorial Sloan Kettering Cancer Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
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.
Drug: Cyclophosphamide
Cyclophosphamide (10mg/kg/day x 4days)
Drug: Fludarabine
Fludarabine (30mg/m^2/day x 5 days)
Radiation: Total body irradiation (TBI)
TBI (450 cGY in a single fraction)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence & Quality of Engraftment & Hematopoietic Reconstitution
Time Frame: 8 years
Number of patients who engrafted
8 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI)
Miltenyi Biotec, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2001

Primary Completion (Actual)

May 1, 2013

Study Completion (Actual)

May 1, 2013

Study Registration Dates

First Submitted

January 7, 2008

First Submitted That Met QC Criteria

January 15, 2008

First Posted (Estimate)

January 16, 2008

Study Record Updates

Last Update Posted (Estimate)

August 10, 2016

Last Update Submitted That Met QC Criteria

June 29, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 01-062

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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