Use of Rft5-Dga to Deplete Alloreactive Cells for Pts With Fanconi Anemia After Haploidentical SCT

Summary

While stem cell transplantation has proven an effective means of treating a wide variety of diseases involving hematopoietic stem cells and their progeny, a shortage of donors has proved a major impediment to the widest application of the approach. Until recently, only MHC identical donors could be used with safety. Such donors were originally siblings or other closely related family members. Over the past decade, the growth of allogeneic donor panels has allowed transplantation with stem cells obtained from a volunteer donor panel.

While it is now possible to obtain HLA identical unrelated donor stem cells for approximately 75% of individuals of Northern European backgrounds, the situation for most other ethnic groups is much less satisfactory. Even when a matched donor can be found, the elapsed time between commencing the search and collecting the stem cells usually exceeds three months, a delay that may doom many of the neediest patients. Hence there has been considerable interest in making use of HLA haploidentical family donors. Most individuals have a first-degree relative who would be suitable for such protocols. Fanconi anemia (FA) is an autosomal recessive disorder characterized by the development of progressive aplastic anemia usually evident by about age seven years and often associated with various diverse congenital anomalies such as short stature, microcephaly, radial anomalies, horseshoe kidney, and cafe au lait spots.

This study will determine the number of donor lymphocytes that can be given to recipients of haploidentical stem cell transplants with Fanconi anemia after depletion of recipient-reactive T lymphocytes by ex-vivo treatment with a fixed dose of RFT5-dgA immunotoxin, and will result in a rate of Grade III/IV GVHD of \< / = 25%.

Conditions

• FANCONI ANEMIA

Interventions

PROCEDURE

CD34 selected haploidentical PBSCT

Infusion of CD34 selected haploidentical PBSCT

DRUG

Fludarabine

day -8 through day -4 Fludarabine 30 mg/m\^2

BIOLOGICAL

T cell infusion

At least 30 days after the stem cell infusion, patients will be dosed with T cells. This study will begin with a dose of T cells known not to cause GvHD even in haploidentical recipients, even when the T cells administered have not first been allodepleted. Dose escalation will follow a traditional up and down method, but as results become available they will be used to determine subsequent dose levels by the continual reassessment method. Initially, 2 patients will be entered beginning at dose level 1. Each and every patient will receive up to three additional injections of T cells at the same dose, at monthly intervals, provided there is no evidence of grade 2 or higher GVHD, until total T cell numbers are \> 1000/ul. Dose level -1 (1 x 10\^3 T cells/Kg); Dose level 1 (1 x 10\^4 T cells/Kg); Dose level 2 (1 x 10\^5 T cells/Kg); Dose level 3 (1 x 10\^6 T cells/Kg); Dose level 4 (5 x 10\^6 T cells/Kg)

BIOLOGICAL

Campath 1h

10 mg iv over 4 hours day-8 through day-6

BIOLOGICAL

anti-CD45

anti-CD45 400 ug/kg over 6 hours day -5 through day -2

Sponsors & Collaborators

• University of Texas, Southwestern Medical Center at Dallas

  collaborator OTHER

• Center for Cell and Gene Therapy, Baylor College of Medicine

  collaborator OTHER

• Baylor College of Medicine

  lead OTHER

Principal Investigators

• Malcolm Brenner, MB, PhD · Baylor College of Medicine

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

64 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2002-03-31

Primary Completion

2009-07-31

Completion

2009-07-31

Countries

• United States

Study Locations