Related Hematopoietic Stem Cell Transplantation (HSCT) for Genetic Diseases of Blood Cells

Summary

Many genetic diseases of lymphohematopoietic cells (such as sickle cell anemia, thalassemia, Diamond-Blackfan anemia, Combined Immune Deficiency (CID), Wiskott-Aldrich syndrome, chronic granulomatous disease, X-linked lymphoproliferative disease, and metabolic diseases affecting hematopoiesis) are sublethal diseases caused by mutations that adversely affect the development or function of different types of blood cells. Although pathophysiologically diverse, these genetic diseases share a similar clinical course of significant progressive morbidity, overall poor quality of life, and ultimate death from complications of the disease or its palliative treatment. Supportive care for these diseases includes chronic transfusion, iron chelation, and surgery (splenectomy or cholecystectomy) for the hemoglobinopathies; prophylactic antibiotics, intravenous immunoglobulin, and immunomodulator therapies for the immune deficiencies; and enzyme replacement injections and dietary restriction for some of the metabolic diseases. The suboptimal results of such supportive care measures have led to efforts to implement more aggressive therapeutic interventions to cure these lymphohematopoietic diseases. The most logical strategies for cure of these diseases have been either replacement of the patient's own hematopoietic stem cells (HSC) with those derived from a normal donor allogeneic bone marrow transplant (BMT) or hematopoietic stem cell transplant (HSCT), or to genetically modify the patient's own stem cells to replace the defective gene (gene therapy).

Conditions

• Stem Cell Transplantation
• Bone Marrow Transplantation
• Peripheral Blood Stem Cell Transplantation
• Allogeneic Transplantation
• Genetic Diseases
• Thalassemia
• Pediatrics
• Diamond-Blackfan Anemia
• Combined Immune Deficiency
• Wiskott-Aldrich Syndrome
• Chronic Granulomatous Disease
• X-linked Lymphoproliferative Disease
• Metabolic Diseases

Interventions

DRUG

Cyclophosphamide Dose Level 1

given by IV at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. After ten patients the de-escalation will begin if the stopping rule is not met.

DRUG

Cyclophosphamide Dose Level 2

Level 2 will be 70mg/kg in 2 divided given once a day for 2 days;

DRUG

Cyclophosphamide Dose Level 3

Level 3 will be 35mg/kg as a one-time dose.

DRUG

Cyclophosphamide Dose Level 4

Level 4 will be no cytoxan.

Sponsors & Collaborators

• Lucile Packard Children's Hospital

  collaborator OTHER

• Children's Hospital Los Angeles

  lead OTHER

Principal Investigators

• Neena Kapoor, M.D. · Children's Hospital Los Angeles

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

3 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-02-28

Primary Completion

2013-09-30

Completion

2014-02-28