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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02512679
• Date of registration: 21/05/2015
• Prospective Registration: No
• Primary sponsor: Children's Hospital Los Angeles
• Public title: Related Hematopoietic Stem Cell Transplantation (HSCT) for Genetic Diseases of Blood Cells
• Scientific title: Protocol for Related Donor Hematopoietic Stem Cell Transplantation (HSCT) for Treatment of Symptomatic Genetic Lymphohematological Diseases
• Date of first enrolment: February 2007
• Target sample size: 20
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02512679
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Contacts

• Name: Neena Kapoor, M.D.
• Affiliation: Children's Hospital Los Angeles

Key inclusion & exclusion criteria

Inclusion Criteria:

- All patients with lethal or sublethal genetic lymphohematological disease (such as
Hemaphagocytic lymphohistiocytosis (HLH) / Familial Erythrophagocytic
Lymphohistiocytosis (FEL), Hurler's Syndrome, Hunter's Syndrome, Kostmann's Syndrome,
Blackfan-Diamond Anemia, Chronic granulomatous Disease (CGD), Red Cell Aplasia, CID,
Sickle Cell Anemia, Thalassemia, Adreno-leukodystrophy, metachromatic leukodystrophy,
Wiskott-Aldrich Syndrome, X-Linked Lymphoproliferative Disease (XLD), Metabolic
diseases affecting hematopoiesis, but not limited to), who are candidates for
allogeneic transplantation for their disease and have a histocompatible sibling or
related donor, ages 0 to 21 years, will be candidates for this study protocol. The
suitable related donor is a 10/10 or 9/10 allele Human Leukocyte Antigen (HLA) match
with the patient. All patients who have previously had serious life- threatening
events due to disease process may be included in the study. Patients must have
adequate physical function and vital organ function to tolerate transplant procedure,
as measured by:

- Cardiac: Shortening fraction >26% or left ventricular ejection fraction at rest must
be > 40%.

- Hepatic: Bilirubin, Alanine Aminotransferase (ALT) and Aspartate Aminotransferase
(AST) < 3x upper limit of normal (as per local laboratory) for age (with the exception
of isolated hyperbilirubinemia due to Gilbert's syndrome).

- Renal: Serum creatinine < 2x upper limit of normal for age or if serum creatinine
elevated beyond normal range patient must have creatinine Clearance or Glomerular
filtration rate (GFR) >50% lower limit of normal for age.

- Pulmonary: Forced expiratory volume (FEV)1, Forced Vital Capacity (FVC), and Diffusing
Lung Capacity for Carbon Monoxide (DLCO) (corrected for Hgb) > 50% predicted. For
patients where pulse oximetry is performed, O2 saturation > 92%

- Evaluation of iron status in patients who have received more than 12 red cell
transfusions. Measurements of serum ferritin levels and MRI of the liver and heart
tissue will evaluate the iron stores. If high iron load is identified in these organs
further evaluation will be done to determine the suitability as transplant recipient.
Should these studies indicate that chelation is necessary the following should apply:
That the treating hematologist will provide the specific chelation type and timing.
Evaluation of organ iron load will be part of the HSCT work-up and if high iron load
is identified then the BMT team will work with the hematologist attending in
developing a plan for the patient.

Exclusion Criteria:

- Karnofsky performance status < 70%, or Lansky < 40% for patients < 16 years old.

- Uncontrolled bacterial, viral, or fungal infections (currently taking medication yet
clinical symptoms progress).

- Seropositivity for the human immunodeficiency virus (HIV).

- Acute active hepatitis.

- Diagnosis of end-organ dysfunction that precludes the ability to tolerate the
transplant procedure.

- Patients with a diagnosis of Fanconi Anemia are excluded.



Age minimum: 3 Months
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Allogeneic Transplantation

Genetic Diseases

Combined Immune Deficiency

Metabolic Diseases

Thalassemia

Wiskott-Aldrich Syndrome

Peripheral Blood Stem Cell Transplantation

Pediatrics

Chronic Granulomatous Disease

Stem Cell Transplantation

Bone Marrow Transplantation

X-linked Lymphoproliferative Disease

Diamond-Blackfan Anemia

Intervention(s)

Drug: Cyclophosphamide Dose Level 1

Drug: Cyclophosphamide Dose Level 2

Drug: Cyclophosphamide Dose Level 3

Drug: Cyclophosphamide Dose Level 4

Primary Outcome(s)

Number of Participants Who Developed Severe Mucositis, Veno-occlusive Disease (VOD), Toxicity of the Kidney, Liver, or Gastrointestinal (GI) Tract up to 1 Year Post-transplant [Time Frame: 1 year]

Number of Participants With Neutrophil Engraftment (=/>500 Cells/uL) and Platelet Engraftment (>20K Cell/uL) at 30 Days [Time Frame: 30 days]

Number of Participants With Disease Recurrence at 1 Year Post-transplant [Time Frame: 1 year]

Secondary Outcome(s)

Number of Participants Who Were Disease Progression-Free and Death-Free at 1 Year Post-transplant [Time Frame: 1 yr]

Number of Participants Who Developed Graft-Versus-Host-Disease (GVHD) as Determined by the Glucksberg Scale [Time Frame: 1 yr]

Secondary ID(s)

CCI-06-00177

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Lucile Packard Children's Hospital

Results

• Results available: Yes
• Date Posted: 17/06/2016
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02512679