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

NCT00586274 | Terminated Phase 1 DMC

• 1 other identifier: H-11428
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 2

Brief 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

Keywords

Stem Cell Transplant; Anemia; Fanconi

Outcome Measures

Primary Outcomes (1)

• Determine # of donor lymphocytes that can be given to recipients of haplo-SCT with FA after depletion of recipient-reactive T lymphocytes by ex-vivo tx with a fixed dose of RFT5-dgA immunotoxin, and will result in Grade III/IV GVHD of < / = 25%.

  1 yr

Secondary Outcomes (2)

• To analyze immune reconstitution in these patients.

  1 yr

• To measure their overall and disease free survival, at 100 days and at 1 year after transplant.

  1 yr

Study Arms (1)

CD34 selected haploidentical PBSCT

EXPERIMENTAL

CD34 selected haploidentical PBSCT

Procedure: CD34 selected haploidentical PBSCT; Drug: Fludarabine; Biological: T cell infusion; Biological: Campath 1h; Biological: anti-CD45

Interventions

CD34 selected haploidentical PBSCT PROCEDURE

Infusion of CD34 selected haploidentical PBSCT

CD34 selected haploidentical PBSCT

Fludarabine DRUG

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

CD34 selected haploidentical PBSCT

T cell infusion BIOLOGICAL

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)

CD34 selected haploidentical PBSCT

Campath 1h BIOLOGICAL

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

CD34 selected haploidentical PBSCT

anti-CD45 BIOLOGICAL

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

CD34 selected haploidentical PBSCT

Eligibility Criteria

• Age: Up to 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• At the time of eligibility for infusion of allodepleted T -cells patients must satisfy the criteria below:
• Patients with Fanconi anemia of all ages with severe aplasia (as evidenced by hypocellular bone marrow) who lack a suitable conventional related (i.e. 5/6 or 6/6 related) or 5/6 or 6/6 unrelated donor with at least 2 out of 3 of the following: a) ANC \< 500/mm3, b) reticulocytes \< 1% c) platelets \< 50,000/mm3
• Diagnosis of Fanconi anemia confirmed by studies of peripheral blood or bone marrow sensitivity to mitomycinC or DEB prior to stem cell transplant. Have received a related haploidentical CD34-selected peripheral blood stem cell transplant with evidence of a full or partial hematopoietic donor chimerism (\> 50%) in the peripheral blood.

You may not qualify if:

• Patients with a life expectancy (\< 6 weeks) limited by diseases other than FA
• Patients with active GVHD \> / = Grade II
• Patients with severe renal disease (i.e. creatinine greater than 3 X normal for age)
• Patients with severe hepatic disease (direct bilirubin greater than 3ug/dl or SGPT greater than 500ug/dl)
• Patients with a severe intercurrent infection
• Lansky scale \< 60 or Karnofsky \< 60

Sponsors & Collaborators

• Baylor College of Medicine: lead
• University of Texas, Southwestern Medical Center at Dallas: collaborator
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (2)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

The Methodist Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Fanconi Anemia; Anemia

Interventions

fludarabine; Alemtuzumab

Condition Hierarchy (Ancestors)

Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Malcolm Brenner, MB, PhD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 21, 2007
• First Posted: January 4, 2008
• Study Start: March 1, 2002
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: March 4, 2014

Record last verified: 2014-03

Locations

US (2)