T Cell Depletion for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts

Summary

Subjects are being asked to participate in this study because treatment of their disease requires them to receive a stem cell transplant. Stem cells or "mother" cells are the source of normal blood cells and lead to recovery of blood counts after bone marrow transplantation (BMT). Unfortunately, there is not a perfectly matched stem cell donor (like a sister or brother) and the subject's disease is considered rapidly progressive and does not permit enough time to identify another donor (like someone from a registry list that is not their relative). We have, however, identified a close relative of the subject's whose stem cells are not a perfect match, but can be used. However, with this type of donor, there is typically an increased risk of developing graft-versus-host disease (GVHD), a high rate of transplant failure, and a longer delay in the recovery of the immune system.

GVHD is a serious and sometimes fatal side effect of stem cell transplant. GVHD occurs when the new donor cells (graft) recognizes that the body tissues of the patient (host) are different from those of the donor. When this happens, cells in the graft may attack the host organs, primarily the skin, liver, and intestines. The number of occurrences and harshness of severe GVHD depends on several factors, including the degree of genetic differences between the donor and recipient, the intensity of the pre-treatment conditioning regimen, the quantity of transplanted cells, and the recipient's age. In recipients of mismatched family member or matched unrelated donor stem cell transplants, there is a greater risk of GVHD so that 70-90% of recipients of unchanged marrow will develop severe GVHD which could include symptoms such as marked diarrhea, liver failure, or even death.

In an effort to lower the occurrences and severity of graft-versus-host disease in patients and to lower the rate of transplant failure, we would like to specially treat the donor's blood cells to remove cells that are most likely to attack the patient's tissues. This will occur in combination with intense conditioning treatment that the patient will receive before the transplant.

Conditions

• Acute Lymphoblastic Leukemia
• Non Hodgkins Lymphoma
• Myelodysplastic Syndrome
• Acute Myeloid Leukemia
• Chronic Myelogenous Leukemia
• Hemophagocytic Lymphohistiocytosis (HLH)
• Familial Hemophagocytic Lymphohistiocytosis (FLH)
• Viral-associated Hemophagocytic Syndrome (VAHS)
• X-linked Lymphoproliferative Disease (XLP)

Interventions

DRUG

Ara-C

day-8 through day-5 3 g/m2 q 12 hours

DRUG

Cyclophosphamide

day-7 and day-6 45 mg/kg

BIOLOGICAL

Campath-1H

day-3 through day-1 Dosing for children: 5 - 15kg : 3mg IV in 30ml NS 15.1 - 30kg : 5mg IV in 50ml NS \>30 kg : 10mg IV in 100ml NS Adults will receive 10mg IV in 100ml NS

RADIATION

Total Body Irradiation

day-4 through day-1 175 cGy x 2 at 24 cGy/min

PROCEDURE

Stem Cell Infusion

Stem cells are infused on day 0

Sponsors & Collaborators

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

  collaborator OTHER

• The Methodist Hospital Research Institute

  collaborator OTHER

• Baylor College of Medicine

  lead OTHER

Principal Investigators

• Robert A. Krance, MD · Baylor College of Medicine

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

55 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2000-04-30

Primary Completion

2015-11-30

Completion

2016-11-30

Countries

• United States

Study Locations