Unrelated HSCT in Patients With Fanconi Anemia

July 6, 2017 updated by: Neena Kapoor, M.D.

A Study of Total Body Irradiation, Cyclophosphamide and Fludarabine Followed by Alternated Donor Hematopoietic Cell Transplantation in Patients With Fanconi Anemia

The protocol is designed for the compassionate treatment of patients with Fanconi Anemia who do not have an HLA-matched sibling donor. The purpose of this study is to determine the likelihood of engraftment in Fanconi Anemia patients using total body irradiation (TBI), cyclophosphamide (CY), fludarabine (FLU) and antithymocyte globulin (ATG) followed by an unrelated donor hematopoietic cell transplant with T-cell depletion using the CliniMACS device.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

The major obstacle to successful alternate donor HCT for patients with Fanconi Anemia is graft failure. While T-cell depletion decreases the incidence of aGVHD, its effect on improving long term survival is unproven. To potentially improve engraftment rate, we have chosen a relatively new immunosuppressive agent, fludarabine (FLU), FLU is an antineoplastic agent that has been shown to be an effective immunosuppressive agen in BMT conditioning therapy. The addition of FLU to the commonly used preparative regimen of CY and TBU in Fanconi Anemia patients may improve engraftment rates.

Based on all presented data and its outcome, hematopoietic stem cell transplantation with the use of total body irradiation (450 cGy), cyclophosphamide (10 mg/kg IV) and fludarabine (35 mg/m2 IV) as preparative cytoreductive therapy has become the standard treatment for the hematologic manifestations of Fanconi Anemia at CHLA. However, the use of Isolex 300i will be replaced by CliniMACS in processing T-cell depletion.

The CliniMACS CD34 Reagent System is an investigational medical device that has not yet been approved by the FDA. This device is used in vitro to select and enrich specific cell populations. When using the CliniMACS CD34 Reagent, the system selects CD34+ cells from heterogenous hematological cell populations for transplantation in cases where this is clinically indicated. Based on the gathered data, CliniMACS has not been a contributing factor in the toxicity of patients, although may have a potential of eliciting "antibody" reactions in some patients, the process has been of significant life-saving benefit as compared to the potential risks.

Study Type

Interventional

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

    • California
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles

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

1 month to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients must be > 2 months and < 21 years of age with a diagnosis of Fanconi anemia.
  • Patients must have an HLA-A, B, DRB1 identical or 1 antigen mismatched related (non-sibling) or unrelated 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 a 2 antigen mismatched related donor will be eligible for the protocol but evaluated separately).
  • Patients with FA must have high risk genotype or aplastic anemia (AA) or myelodysplastic syndrome without excess blasts.
  • Aplastic anemia is defined as having at least one of the following:

    1. platelet count <20 x 109/L
    2. ANC <5 x 108/L
    3. Hgb <8 g/dL with at least one of the following:
    1. transfusion dependence
    2. supportive care toxicity
  • Myelodysplastic syndrome with multilineage dysplasia with or without chromosomal anomalies.
  • High risk genotype (e.g. IVS-4 or exon 14 FANCC mutations)
  • Adequate major organ function including:
  • Cardiac: ejection fraction >45%
  • Renal: creatinine clearance >40 mL/min.
  • 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:

  • Available HLA-genotypically identical related donor.
  • The harvested marrow (prior to TCD) should contain a minimum of 2.5 x 108 nucleated cells/kg recipient body weight with a goal of >5.0 x 108 nucleated cells/kg recipient body weight.
  • Positive lymphocytotoxic crossmatch against donor (T cells and B cells)
  • History of gram negative sepsis or systemic fungal infection (proven or suspected based on radiographic studies).
  • Myelodysplastic syndrome with excess blasts or leukemia.
  • Active CNS leukemia at time of HCT.
  • Malignant solid tumor (e.g. squamous cell carcinoma of the head/neck/cervix) within 2 years of HCT.
  • Pregnant or lactating female.
  • Prior radiation therapy preventing use of TBI 450 cGy.

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
Other: CD34+ selected cells
use of unrelated bone marrow or peripheral blood for hematopoietic stem cell transplantation with CD34+ selected cells
Compassionate treatment of Fanconi Anemia patients with unrelated bone marrow or peripheral blood HSCT followed by the infusion of CD34+ selected cells using CliniMACS
Other Names:
  • CD34+ selected cells using CliniMACS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event free survival post stem cell transplant
Time Frame: 5 years
Patients who are alive at 5 years post transplants with assessments at 30, 60, 90, 180 and yearly up to 5 years
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peripheral blood CBC counts for engraftment evaluation
Time Frame: 3 years
Normalization of Hemoglobin, platelets and neutrophil count
3 years
Chimerism assay for engraftment evaluation
Time Frame: 3 years
Assessment of chimerism by FISH or STR on peripheral blood and bone marrow
3 years
Graft Versus Host Disease (GVHD) surveillance after HSCT
Time Frame: 3 years
GHVD disease surveilance done by clinical evaluation, to include history, physical examination, specifically for rash, jaundice, liver dysfunction, nausea and vomiting, diarrhea and failure to thrive
3 years

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Neena Kapoor, M.D., Children's Hospital Los Angeles, University of Southern California

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 (Anticipated)

March 1, 2011

Primary Completion (Actual)

March 1, 2016

Study Completion (Actual)

March 1, 2016

Study Registration Dates

First Submitted

October 19, 2012

First Submitted That Met QC Criteria

April 29, 2014

First Posted (Estimate)

May 1, 2014

Study Record Updates

Last Update Posted (Actual)

July 11, 2017

Last Update Submitted That Met QC Criteria

July 6, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Procedure as well as de-identified data is reported to CIBMTR and is available to other researchers.

IPD Sharing Time Frame

End of subject enrollment and following 2 year subject follow-up

IPD Sharing Access Criteria

Researchers/Investigators interested in severe combined immune deficiency disease treatment and outcomes.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Clinical Study Report (CSR)

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.

Clinical Trials on Fanconi Anemia

Clinical Trials on CD34+ selected cells

3
Subscribe