Reduced Intensity Conditioning for Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT

Launched by PAUL SZABOLCS · Oct 10, 2013

Keywords

ClinConnect Summary

This clinical trial is exploring a new approach for treating certain non-cancerous blood disorders using a less intense conditioning method before a stem cell transplant. Specifically, it focuses on patients with conditions like primary immunodeficiency, congenital bone marrow failure, inherited metabolic disorders, hereditary anemias, and inflammatory conditions. The goal is to see how effective this reduced-intensity method is when using umbilical cord blood or bone marrow from matched donors for transplantation. After the procedure, doctors will monitor patients for any long-term effects and to ensure the transplanted cells are working well.

To be eligible for this trial, participants should have a suitable donor and meet specific health criteria, such as having good organ function and no active infections. This trial is open to individuals aged 60 and older, and all genders are welcome to participate. If someone qualifies and chooses to join, they can expect close follow-up care after the transplant to track their recovery and any potential side effects. Overall, this trial aims to improve treatment options for patients with these serious but non-malignant disorders.

Gender

ALL

Eligibility criteria

• Inclusion:
• • 1. A 4/6, 5/6 or 6/6 HLA matched related or unrelated UCB unit available that will deliver a pre-cryopreservation total nucleated cell dose of ≥ 3 x 10e7 cells/kg, or double unit grafts, each cord blood unit delivering at least 2 x 10e7 cells/kg OR an 8 of 8 or 7 of 8 HLA allele level matched unrelated donor bone marrow or peripheral blood progenitor graft.
• 2. Adequate organ function as measured by:
• • 1. Creatinine ≤ 2.0 mg/dL and creatinine clearance ≥ 50 mL/min/1.73 m2.
• • 2. Hepatic transaminases (ALT/AST) ≤ 4 x upper limit of normal (ULN).
• • 3. Adequate cardiac function by echocardiogram or radionuclide scan (shortening fraction \> 26% or ejection fraction \> 40% or \> 80% of normal value for age).
• • 4. Pulmonary evaluation testing demonstrating CVC or FEV1/FVC of ≥ 50% of predicted for age and/or resting pulse oximeter ≥ 92% on room air or clearance by the pediatric or adult pulmonologist. For adult patients DLCO (corrected for hemoglobin) should be ≥ 50% of predicted if the DLCO can be obtained.
• • 3. Written informed consent and/or assent according to FDA guidelines.
• • 4. Negative pregnancy test if pubertal and/or menstruating.
• • 5. HIV negative.
• 6. A non-malignant disorder amenable to treatment by stem cell transplantation, including but not limited to:
• 1. Primary Immunodeficiency syndromes including but not limited to:
• • Severe Combined Immune Deficiency (SCID) with NK cell activity
• • Omenn Syndrome
• • Bare Lymphocyte Syndrome (BLS)
• • Combined Immune Deficiency (CID) syndromes
• • Combined Variable Immune Deficiency (CVID) syndrome
• • Wiskott-Aldrich Syndrome
• • Leukocyte adhesion deficiency
• • Chronic granulomatous disease (CGD)
• • X-linked Hyper IgM (XHIM) syndrome
• • IPEX syndrome
• • Chediak - Higashi Syndrome
• • Autoimmune Lymphoproliferative Syndrome (ALPS)
• • Hemophagocytic Lymphohistiocytosis (HLH) syndromes
• • Lymphocyte Signaling defects
• • Other primary immune defects where hematopoietic stem cell transplantation may be beneficial
• 2. Congenital bone marrow failure syndromes including but not limited to:
• • Dyskeratosis Congenita (DC)
• • Congenital Amegakaryocytic Thrombocytopenia (CAMT)
• • Osteopetrosis
• 3. Inherited Metabolic Disorders (IMD) including but not limited to:
• • Mucopolysaccharidoses
• • Hurler syndrome (MPS I)
• • Hunter syndrome (MPS II)
• • Leukodystrophies
• • Krabbe Disease, also known as globoid cell leukodystrophy
• • Metachromatic leukodystrophy (MLD)
• • X-linked adrenoleukodystrophy (ALD)
• • Hereditary diffuse leukoencephalopathy with spheroids (HDLS)
• • Other inherited metabolic disorders
• • alpha mannosidosis
• • Gaucher Disease
• • Other inheritable metabolic diseases where hematopoietic stem cell transplantation may be beneficial.
• • 4. Hereditary anemias
• • Thalassemia major
• * Sickle cell disease (SCD) - patients with sickle disease must have one or more of the following:
• • Overt or silent stroke
• • Pain crises ≥ 2 episodes per year for past year
• • One or more episodes of acute chest syndrome
• • Osteonecrosis involving ≥ 1 joints
• • Priapism
• • Diamond Blackfan Anemia (DBA)
• • Other congenital transfusion dependent anemias
• • 5. Inflammatory Conditions
• • Crohn's Disease/Inflammatory Bowel Disease
• Exclusion:
• • 1. Allogeneic hematopoietic stem cell transplant within the previous 6 months.
• • 2. Any active malignancy or MDS.
• • 3. Severe acquired aplastic anemia.
• • 4. Uncontrolled bacterial, viral or fungal infection (currently taking medication and with progression of clinical symptoms).
• • 5. Pregnancy or nursing mother.
• • 6. Poorly controlled pulmonary hypertension.
• • 7. Any condition that precludes serial follow-up.