Reduced Intensity Conditioning for Umbilical Cord Blood Transplant in Pediatric Patients With Non-Malignant Disorders

Duke University

Status and phase

Completed

Phase 1

Conditions

Thalassemia

Non Malignant Disorders

Inborn Errors of Metabolism

Hemoglobinopathies

Lysosomal Storage Disease

Immunodeficiencies

Congenital Marrow Failures

Sickle Cell

Treatments

Drug: Reduced Intensity Conditioning

Biological: Unrelated Umbilical Cord Blood Transplant

Study type

Interventional

Funder types

Other

Identifiers

NCT00744692

Pro00008753

Details and patient eligibility

About

The primary objective is to determine the feasibility of attaining acceptable rates of donor cell engraftment (>25% donor chimerism at 180 days) following reduced intensity conditioning (RIC) regimens in pediatric patients < 21 years receiving cord blood transplantation for non-malignant disorders.

Full description

Myeloablative doses of chemotherapy and/or radiation therapy are employed with the primary purpose of eradicating malignant cells. Additionally, these regimens exert varying degree of immunosuppression/immunoablation that aids in reducing the likelihood of rejection by host hematopoietic cells. However, myeloablative /immunoablative regimens have also been associated with significant regimen related toxicity (RRT) and regimen related mortality (RRM) that may cause death in up to 20% of patients and significantly higher rate of severe organ dysfunction or failure. While most of these RRT occur typically in the first 100 days [ e.g. VOD (veno occlusive disease), pulmonary or intracranial hemorrhage, multiorgan failure (MOF)], there are significant long term toxicities of TBI and/or chemotherapy including growth impairment, gonadal dysfunction/failure, hypothyroidism, cataracts, neurocognitive impairment, and second malignancies.

The secondary objectives are:

To describe the pace of neutrophil and platelet recovery
To evaluate the pace of immune reconstitution.
To determine the treatment related mortality, overall survival and disease free survival by days 100 and 180 post-transplant
To describe incidence of acute Graft Versus Host Disease (GVHD) (II - IV) and chronic extensive GVHD
To describe the incidence of grade 3-4 organ toxicity
To evaluate long-term complications, such as sterility, endocrinopathy, and growth failure
To evaluate the incidence of late graft failures at 2 years post-transplant

Enrollment

22 patients

Sex

All

Ages

Under 21 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

0-21 years of age with a diagnosis of a immunodeficiency, congenital marrow failure syndrome, inborn error of metabolism, or hereditary anemia
Appropriately matched related or unrelated umbilical cord blood unit with a cell dose ≥ 3 x 10e7cells/kg
Performance score (lansky or karnofsky) greater than or equal to 70
Adequate organ function (Creatinine ≤ 2.0 mg/dl and creatinine clearance ≥ 50 ml/min/1.73 m2; Hepatic transaminases (ALT/AST) ≤ 4 x normal; Shortening fraction >26% or ejection fraction >40% or > 80% of normal value for age; Pulmonary function tests demonstrating CVC or FEV1/FVC of >60% of predicted for age.)
Informed consent
Not pregnant or breast feeding
Minimum life expectancy of at least 6 months
HIV negative
No uncontrolled infections at the time of cytoreduction
Disease specific inclusion criteria

Exclusion criteria

Patients with hemoglobinopathies > 3 years of age
UCB unit with a total nucleated cell count < 3 x 10e7/kg or > 2 antigen mismatching
Available HLA-matched related living donor able to donate without previous UCB donation
Allogeneic hematopoietic stem cell transplant within the previous 6 months
Any active malignancy, MDS, or any history of malignancy
Severe acquired aplastic anemia
DLCO < 60% of normal value for age; requirement for supplemental oxygen
Uncontrolled bacterial, viral or fungal infection (currently taking medication and progression of clinical symptoms)
Pregnancy or nursing mother
HIV/HTLV seropositive, Hep B surface antigen positive, or HCV RNA positive by PCR
Any condition that precludes serial follow-up