Clinical Trial Finder

Inclusion Criteria:

• - Appropriate diagnosis: Patients must have a disease or syndrome amenable to therapy with hematopoietic stem cell transplantation.

Diagnoses include, but are not limited to:

• - Congenital and Other Non-malignant Disorders: - Immunodeficiency disorders (e.g. Severe Combined Immunodeficiency, Wiskott-Aldrich Syndrome) - Congenital hematopoietic stem cell defects (e.g. Chediak-Higashi Syndrome, Congenital Osteopetrosis, Osteogenesis Imperfecta) - Metabolic disorders (e.g. Hurler's Syndrome) - Severe aplastic anemia.

• - High-Risk Leukemia: - Acute Myelogenous Leukemia.

• - Refractory to standard induction therapy (more than 1 cycle required to achieve remission) - Recurrent (in CR ≥ 2) - Treatment-related AML or MDS.

• - Evolved from myelodysplastic syndrome.

• - Presence of FLT3 abnormalities.

• - FAB M6 or M7.

• - Adverse cytogenetics.

• - Myelodysplastic Syndrome.

• - Acute Lymphoblastic Leukemia including T lymphoblastic leukemia: - Refractory to standard induction therapy (time to CR >4 weeks) - Recurrent (in CR ≥ 2) - WBC count >30,000/mcL at diagnosis.

• - Age >30 at diagnosis.

• - Adverse cytogenetics, such as t(9:22), t(1:19), t(4:11), and other MLL rearrangements.

• - Chronic Myelogenous Leukemia in accelerated phase or blast crisis.

• - Biphenotypic or undifferentiated leukemia.

• - Burkitt's leukemia or lymphoma.

• - Lymphoma: - Large cell, Mantle cell, Hodgkin lymphoma refractory or recurrent, chemo-sensitive, and ineligible for an autologous stem cell transplant or previously treated with autologous SCT.

• - Marginal zone or follicular lymphoma that is progressive after at least two prior therapies.

• - Multiple Myeloma, recurrent following high-dose therapy and autologous SCT or ineligible for an autologous HSCT.

• - Solid tumors, with efficacy of allogeneic HSCT demonstrated for the specific disease and disease status.

• - Adequate organ function: - Cardiac - LVEF >45%, or shortening fraction >25%, Absence of congestive heart failure or conduction disturbances with high risk for sudden death.

• - Pulmonary - DLCO (corrected for hemoglobin), FEV1 and FVC ≥ 50% predicted; - Renal - serum Cr < 1.5 times the upper limit of normal for age or GFR ≥ 50 ml/min/1.73m2.

• - Hepatic - total bilirubin level < 2 times the upper limit of normal (except for patients with Gilbert's syndrome or hemolysis); if the primary disease process is causal, this criterion will be reconsidered.

ALT, AST, and Alkaline phosphatase ≤ 5 times upper limit of normal.

• - Performance Status Karnofsky or Lansky score ≥ 70%.

• - Informed Consent must be obtained prior to initiating conditioning therapy.

• - Receipt of viable cord blood product(s), single or dual, must be confirmed with the stem cell processing laboratory prior to initiating conditioning therapy.

Exclusion Criteria:

• - Availability of 10/10 or 9/10 HLA-matched related or unrelated donor within a reasonable timeframe dictated by the clinical urgency of the transplant.

• - Autologous HSCT < 6 months prior to proposed UCB transplant.

• - Pregnant or breast feeding.

• - Current uncontrolled infection.

- Evidence of HIV infection or positive HIV serology

This study is a single-center treatment protocol with four possible preparative regimens, designed to validate the process of umbilical cord blood stem cell transplantation at our institution. Enrolled patients will receive chemotherapy +/-total body radiation as a pre-transplant conditioning regimen. Patients will then receive cord blood stem cells followed by GvHD prophylaxis that will include Tacrolimus and Mycophenolate Mofetil, or Cyclosporin A and Methylprednisolone. Multiple data points will be collected prior to, during, and following transplantation to ensure safety of the process and to evaluate the stated objectives.

Arms

Other: Full Intensity, TBI-based Conditioning

Full Intensity TBI-based Conditioning Total Body Irradiation 1200 cGy in fractions of 150 cGy days -8 or -7 to -4 Cyclophosphamide 60 mg/kg/day x 2 doses days -3 and -2 Mesna 60 mg/kg/day with 20% loading dose with first Cyclophosphamide followed by continuous infusion over 24 hours x 2 doses [to be completed 24 hours after final Cyclophosphamide dose] followed by Cord Blood Infusion Other names: TBI/Cy

Other: Full Intensity, Chemo-based Conditioning

Full Intensity, Chemotherapy Conditioning Busulfan days -7 to -4 Recipients <5 years - 1 mg/kg/dose x 16 doses every 6 hours Recipients >/= 5 years - 0.8 mg/kg/dose x 16 doses every 6 hours Cyclophosphamide 60 mg/kg/day x 2 doses days -3 and -2 Mesna 60 mg/kg/day with 20% loading dose with first Cyclophosphamide followed by continuous infusion over 24 hours x 2 doses [to be completed 24 hours after final Cyclophosphamide dose] followed by Cord Blood Infusion Other names: Bu/Cy

Other: Reduced Intensity Chemotherapy

Reduced Intensity Chemotherapy Fludarabine 30 mg/m2/day x 5 doses days -6 to -2 Melphalan 140 mg/m2/day x 1 dose day -2 Cord Blood Infusion Other names: Flu/Mel

Other: Non-Myeloablative Conditioning

Fludarabine 40 mg/m2/day x 5 doses days -6 to -2 Cyclophosphamide 50 mg/kg/day x 1 dose day -6 Mesna 50 mg/kg/day with 20% loading dose with Cyclophosphamide dose followed by continuous infusion over 24 hours x 1 dose [to be completed 24 hours after Cyclophosphamide dose] Total Body Irradiation 200 cGy in a single fraction day -1 Cord Blood Infusion Other names: Flu/Cy/TBI

Interventions

Radiation: - Total Body Irradiation 1200 cGy

Total Body Irradiation 1200 cGy in 8 fractions

Radiation: - Total Body Irradiation 200 cGy

Total Body Irradiation 200 cGy in one fraction

Drug: - Cyclophosphamide

50 mg/kg or 60 mg/kg

Drug: - Mesna

50 mg/kg or 60 mg/kg plus 10% loading dose

Procedure: - Cord Blood Infusion

Intravenous infusion of cord blood stem cells

Drug: - Busulfan

0.8 mg/kg x 16 doses

Drug: - Fludarabine

30 mg/m2/day x 5 or 40 mg/m2/day x 5

Drug: - Melphalan

140 mg/m2