Blood and Lymph Conditions

All Conditions

Neoplasms

Immune System Diseases

Diseases and Abnormalities at or Before Birth

Symptoms and General Pathology

Rare Diseases

Thrombocytopenia

Lymphoma

Leukemia

Anemia, Sickle Cell

Thalassemia

beta-Thalassemia

Anemia

Anemia, Aplastic

Hodgkin Disease

Hematologic Diseases

Anemia, Diamond-Blackfan

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hemolysis

Anemia, Hemolytic

Anemia, Hemolytic, Congenital

Hemoglobinopathies

Genetic Diseases, Inborn

Blood Platelet Disorders

Cytopenia

Bone Marrow Failure Disorders

Pancytopenia

Bone Marrow Diseases

Anemia, Hypoplastic, Congenital

Red-Cell Aplasia, Pure

Syndrome

Congenital Bone Marrow Failure Syndromes

Lymphosarcoma

Beta-thalassemia

Aplastic Anemia

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Sickle Cell Anemia

Diamond-Blackfan Anemia

Severe Congenital Neutropenia

Pure Red Cell Aplasia

Matched allogeneic donor stem cells will be processed utilizing α/β CD3+/CD19+ cell depletion with the Prodigy system. Standard pre-conditioning and post-transplant motioning will be given.

donor cells will be collected and subsequently undergo α/β CD3+/CD19+ cell depletion.

alpha beta depletion

Mitchell S Cairo, MD

Lauren Harrison, RN

Lauren Harrison, MSN

Mitchell S Cairo

Children, adolescents, and young adults with malignant and non-malignant conditionsundergoing an allogeneic stem cell transplantation (AlloSCT) will have the stem cells selected utilizing α/β CD3+/CD19+ cell depletion. All other treatment is standard of care.

Patients wiith selected malignant or non-malignant conditions meeting eligibility criteria will be enrolled on this study. Patients will receive one of either full intensity, reduced intensity, or reduced toxicity conditioning appropriate based on disease, disease status, organ function and performance status and will undergo α/β T-cell and CD 19+ B cell depleted alloSCT.

Patients will be following for engraftment, chimerism, immune reconstitution, GVHD and QOL.

AlloSCT for Malignant and Non-malignant Hematologic Diseases Utilizing Alpha/Beta T Cell and CD19+ B Cell Depletion

Allogeneic Stem Cell Transplantation for Malignant and Non-malignant Hematologic Diseases Utilizing Alpha/Beta T Cell and CD19+ B Cell Depletion - NYMC 588

patients will be monitored for any adverse events related to administration of α/β CD3+/CD19+ cell depleted stem cells

patients will have routine chimerism performed to monitoring engraftment of donor cells

patients will be monitored post transplant for signs of acute and chronic GVHD

Mitchell Cairo

Co-Investgiator

Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Digestive System Diseases

Nutritional and Metabolic Diseases

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Leukemia, Myelomonocytic, Juvenile

Myelodysplastic Syndromes

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Acquired Immunodeficiency Syndrome

HIV Infections

Immunologic Deficiency Syndromes

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Neutropenia

Lymphocytosis

Macrophage Activation Syndrome

Primary Immunodeficiency Diseases

Histiocytosis, Langerhans-Cell

Histiocytosis

Shwachman-Diamond Syndrome

Precancerous Conditions

Myeloproliferative Disorders

Chronic Disease

Disease Attributes

Myelodysplastic-Myeloproliferative Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Granulocytopenia

Langerhans Cell Histiocytosis

Familial Hemophagocytic Lymphohistiocytosis

Sickle Beta Thalassemia

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Pharmaceutical Solutions

Anti-Inflammatory Agents

Anti-Infective Agents

Hematinics

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Tacrolimus

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Melphalan

Prednisolone

Sirolimus

Busulfan

Liver Extracts

Methylprednisolone

Thiotepa

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Alemtuzumab

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Calcineurin Inhibitors

Enzyme Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Protective Agents

Antineoplastic Agents, Hormonal

Antineoplastic Agents, Immunological

Patients will start their pre-conditioning regimen on 8 days before scheduled transplant. Fractionated total body irradiation (TBI) will be administered twice daily on the 6th, 7th, and 8th before transplant. Patients will receive Thiotepa on the 4th and 5th day before transplant, Cyclophosphamide on the 2nd and 3rd day before transplant, and Alemtuzumab on the 1st-5th day(s) before transplant. Then the stem cell infusion will be performed (allogeneic family member or ≥ 8/10 HLA matched adult unrelated donor peripheral blood stem cell transplantation with CD34 Selection using CliniMACS CD34+ Reagent System). GVHD prophylaxis will consist of tacrolimus only. Tacrolimus administration will begin on the day after transplant, and methylprednisolone will start on day -5.

Patients will start their pre-conditioning regimen 9 days before their scheduled transplant. Patients will receive busulfan twice daily on the 5th-8th day before transplant, and Melphalan on the 2nd-4th days before transplant and Alemtuzumab on the 1st-5th day before transplant. Subjects will then undergo with their stem cell infusion (allogeneic family member or ≥ 8/10 HLA matched adult unrelated donor peripheral blood stem cell transplantation with CD34 Selection using CliniMACS CD34+ Reagent System) and GVHD prophylaxis will consist of tacrolimus only. Tacrolimus administration will begin on the day after their transplant, and methylprednisolone will start on day -5.

Patients will begin tacrolimus 8 days pre-transplant, and then will receive alemtuzumab on the 3rd-7th day pre-transplant; busulfan twice daily on the 5th-8th day pre-transplant; and fludarabine on the 2nd-7th day pre-transplant. Methylprednisolone will start on day -7.The stem cell infusion will be performed (with CD34 Selection using CliniMACS CD34+ Reagent System). GVHD prophylaxis will consist of tacrolimus or sirolimus. For patients with a history of hepatic toxicity and/or high-risk for veno-occlusive disease or other liver toxicity post stem cell transplant, melphalan at 70 mg/m2 will be substituted for Busulfan, followed by fludarabine on the 2nd-7th day before transplant and alemtuzumab on the 3rd-7th day before transplant.

The CliniMACS® Reagent System (Miltenyi Biotec, Germany), is a semi-automated immunomagnetic cell selection medical device that is used in vitro to select and enrich specific cell populations in a closed, sterile environment. The system is comprised of a computer controlled medical device containing a permanent magnet, a closed-system sterile tubing set containing columns coated with a ferromagnetic matrix, and a magnetic cell specific labeling reagent.

CliniMACS CD34+ Reagent System

Standard of care: Thiotepa should be diluted in normal saline (NS) (1-5 mg/ml) and infused over 2 hrs on Days -5, -4. IV fluids should be at maintenance rate (1500 ml/m2). It is recommended that total parental nutrition not being used during Thiotepa administration as amino acid infusions may interfere with Thiotepa metabolism.

Standard of care: Cyclophosphamide (Cytoxan) should be infused over one hour. The drug can be diluted in dextrose water solvent (D5W), NS, or other solutions (250cc) to a maximum concentration of 20 mg/mL.

Standard of care: Each dose of alemtuzumab is to be diluted in D5W or NS (maximum concentration: 0.3 mg/mL) for IV infusion over two hours.

Standard of care: Tacrolimus dosing will be 0.03mg/kg/24 hours as continuous IV infusion or 0.12 mg/kg/day po divided Q8-12 hr

Standard of care: Melphalan 45mg/m2 (1.5 mg/kg IV for children \<1 year of age or \<10 kg) diluted in 0.9% NS to a concentration of 0.1- 0.45mg/ml, given IV over 30 minutes.

Standard of care: Busulfan will be given IV in 0.9% sodium chloride or D5W to a final solution for infusion equal to 10 times the volume of diluent to Busulfex (to a concentration \>0.5 mg/mL), through a central venous access device over 2 hours.

Standard of care: Fludarabine will be given IV in 50-100 ml of D5W or 0.9% sodium chloride, over 30 minutes.

Standard of care: Methylprednisolone will be give IV slow infusion over 15-30 minutes.

Jody Campbell, MPA

Desmarie Sherwood

Diane George, MD

The purpose of this study is to learn more about the effects of (classification determinant) CD34+ stem cell selection on graft versus host disease (GVHD) in children, adolescents, and young adults. CD34+ stem cells are the cells that make all the types of blood cells in the body. GVHD is a condition that results from a reaction of transplanted donor T-lymphocytes (a kind of white blood cell) against the recipient's body and organs. Study subjects will be offered treatment involving the use of the CliniMACS® Reagent System (Miltenyi Biotec), a CD34+ selection device to remove T-cells from a peripheral blood stem cell transplant in order to decrease the risk of acute and chronic GVHD.

This study involves subjects who are diagnosed with a malignant disease, that has either failed standard therapy or is unlikely to be cured with standard non-transplant therapy, who will receive a peripheral blood stem cell transplant. A malignant disease includes the following: Chronic Myeloid Leukemia (CML) in chronic phase, accelerated phase or blast crisis; Acute Myelogenous Leukemia (AML); Myelodysplastic Syndrome (MDS); Juvenile Myelomonocytic Leukemia (JMML); Acute Lymphoblastic Leukemia (ALL); or Lymphoma (Hodgkin's and Non-Hodgkin's).

Graft versus host disease (GVHD) is one of the serious complications following allogeneic stem cell transplantation. The incidence and severity of GVHD increase with the degree of HLA incompatibility between the host and donor. The most reliable way to prevent acute and chronic GVHD is to remove T cells from the graft. However, the incidence of graft failure increases with the efficiency of T cell depletion and low T cell numbers are predictive of graft failure. Immunomagnetic selection of HLA-mismatched CD34+ progenitor cells has demonstrated high levels of T cell depletion and successful engraftment in adult and pediatric patients with the malignant and nonmalignant disease.

CD34+ (Malignant) Stem Cell Selection for Patients Receiving Allogenic Stem Cell Transplant

CD34+ Stem Cell Selection for Patients Receiving a Matched or Partially Matched Family or Unrelated Adult Donor Allogeneic Stem Cell Transplant for Malignant Disease

Acute GVHD will be assessed and graded with standard NCI grading criteria.Evaluated daily while hospitalized, then weekly (1-60 days post-transplant), as clinically indicated (60-365 days post transplant), then 1 year, 1.5 years, 2 years and yearly (366+ days post-transplant)

Will be assessed multiple times while hospitalized, 1-60 days post transplant, 100 days post-transplant, 180 days post-transplant, and 1-year post transplant. Neutrophil engraftment is defined as the first of three days following the neutrophil nadir with an absolute neutrophil count above 500/mm3.

Immune reconstitution studies will be conducted (For T-cell, B-cell, natural killer (NK)-cell and immunoglobulins) 60 days post-transplant, 100 days post-transplant, 150 days post-transplant, 180 days post-transplant, 270 days post-transplant, 1-year post-transplant, and 2 years post transplant.

Will be assessed weekly or more as indicated until 84 or 100 days post-transplant, then as clinically indicated.

Will be assessed multiple times while hospitalized, 1-60 days post transplant, 100 days post-transplant, 180 days post-transplant, and 1-year post transplant.

Chronic GVHD will be assessed and graded with standard NCI grading criteria.

Acute GVHD will be assessed and graded with standard NCI grading criteria.

Chronic GVHD will be assessed and graded with standard NCI grading criteria. Evaluated daily while hospitalized, then weekly (1-60 days post-transplant), as clinically indicated (60-365 days post transplant), then 1 year, 1.5 years, 2

Primary graft rejection is defined as the presence of \< 20% donor cells

The presence of \< 20% donor derived hematopoietic cells in peripheral blood

Diane George

Assistant Professor of Pediatrics, Department of Pediatrics Onc/BMT/Hem

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
AlloSCT for Malignant and Non-malignant Hematologic Diseases Utilizing Alpha/Beta T Cell and CD19+ B Cell Depletion	NCT04099966	Acute Leukemia Severe Aplastic... Non-hodgkin Lym... Hodgkin Lymphom... Kostmann Diamond Blackfa... Amegakaryocytic... Sickle Cell Dis... Beta-Thalassemi...	alpha beta depl...	1 Day - 30 Years	New York Medical College
CD34+ (Malignant) Stem Cell Selection for Patients Receiving Allogenic Stem Cell Transplant	NCT02061800	Chronic Myeloid... Acute Myelogeno... Myelodysplastic... Juvenile Myelom... Acute Lymphobla... Lymphoma (Hodgk...	CliniMACS CD34+... Thiotepa Cyclophosphamid... Alemtuzumab Tacrolimus Melphalan Busulfan Fludarabine Methylprednisol...	- 22 Years	Columbia University

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