CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation

NCT01966367 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: AAAL0156
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This study's goal is to determine the frequency and severity of acute graft versus host disease, to evaluate incidence of primary and secondary graft rejection, to assess event free survival and overall survival, to determine the time to neutrophil and platelet engraftment, to determine the time to immune reconstitution (including normalization of T, B and natural killer (NK) cell repertoire and Immunoglobulin G production), and to establish the incidence of infectious complications including bacterial, viral, fungal and atypical mycobacterial and other infections following CD34+ selection in children, adolescents and young adults receiving an allogeneic peripheral blood stem cell transplant from a family member or unrelated adult donor for a non-malignant disease.

Conditions

Bone Marrow Failure Syndrome; Severe Aplastic Anemia; Severe Congenital Neutropenia; Amegakaryocytic Thrombocytopenia; Diamond-Blackfan Anemia; Schwachman Diamond Syndrome; Primary Immunodeficiency Syndromes; Acquired Immunodeficiency Syndromes; Histiocytic Syndrome; Familial Hemophagocytic Lymphocytosis; Lymphohistiocytosis; Macrophage Activation Syndrome; Langerhans Cell Histiocytosis (LCH); Hemoglobinopathies; Sickle Cell Disease; Sickle Cell-beta-thalassemia

Keywords

Unrelated donor transplant; Haploidentical donor transplant; Peripheral blood stem cell transplantation; CD34+ selection; Non-malignant disease; Bone marrow failure syndrome; Severe Aplastic Anemia; Severe Congenital Neutropenia; Amegakaryocytic Thrombocytopenia; Diamond-Blackfan Anemia; Schwachman Diamond Syndrome; Primary Immunodeficiency Syndrome; Acquired Immunodeficiency Syndrome; Histiocytic Syndrome; Familial Hemophagocytic Lymphocytosis; Lymphohistiocytosis; Macrophage Activation Syndrome; Langerhans Cell Histiocytosis (LCH); Hemoglobinopathies; Sickle Cell Disease; Sickle Cell-beta-thalassemia

Outcome Measures

Primary Outcomes (1)

• Incidence of acute graft versus host disease (GVHD)

  Determine the incidence and severity of acute GVHD.

  100 days

Secondary Outcomes (6)

• Incidence of primary graft failure

  1 year

• Survival Rate

  5 years

• Time to neutrophil and platelet engraftment

  1 year

• Time to immune reconstitution

  2 years

• Incidence of infectious complications

  2 years

Study Arms (1)

CliniMACS PLUS followed by chemotherapy

EXPERIMENTAL

Patients will receive a pre-transplant conditioning regimen of Busulfan Fludarabine and Alemtuzumab. For patients with pre-transplant hepatic dysfunction, Melphalan will be substituted for the Busulfan. For patients receiving a second transplant or a "boost", pre-transplant conditioning based on the clinical condition of the patient will be determined by the Principal Investigator and the patient's bone marrow transplantation (BMT) physician. The donor peripheral blood stem cells will undergo CD34+ selection (Biological/Vaccine: CD34 Stem Cell Selection Therapy). The CliniMACS (PLUS) Reagent System will be used to remove T-cells from the peripheral blood stem cell transplant in order to decrease the risk of acute and chronic graft versus host disease (GVHD).

Biological: CD34 Stem Cell Selection Therapy

Interventions

CD34 Stem Cell Selection Therapy BIOLOGICAL

The CliniMACS (PLUS) Reagent System (Miltenyi CliniMACS CD34+ Cell Selection Device) will be used to remove T-cells from the peripheral blood stem cell transplant in order to decrease the risk of acute and chronic graft versus host disease (GVHD).

CliniMACS PLUS followed by chemotherapy

Eligibility Criteria

• Age: Up to 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• General Eligibility (All Patients)
• Patient must be \< or = 40 years of age. Patients with sickle cell anemia must be at least 2 years of age.
• Patient or the patient's legally authorized guardian must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign an informed consent in accordance with the institutional policies approved by the U.S. Department of Health and Human Services.
• Approval for the use of this treatment protocol by the individual institution's Human Rights Committee must be obtained, in accordance with the institutional assurance policies of the U. S. Department of Health and Human Services.
• Human leukocyte antigen (HLA) typing will be performed by high-resolution molecular DNA typing for HLA Class I A, B, and C and HLA Class II DRB1 and DQB1 alleles.
• Unrelated donor: An 8/10, 9/10 or 10/10 matched unrelated adult donor (MUD) will be required for study entry.
• Related Donor: A 5/10, 6/10, 7/10, 8/10, 9/10 or 10/10 matched (or partially matched) family donor will be required for study entry.
• Non-malignant Disorders per protocol.
• Hemoglobinopathies per protocol.
• Requirement for CD34+ stem cell selection for a second infusion of stem cells following an allogeneic stem cell transplant from a related or unrelated adult donor.
• Additional eligibility for patients with non-malignant disorders receiving myeloablative conditioning
• Adequate renal function as determined by the institutional normal range.
• Adequate liver function per protocol.
• Adequate cardiac function defined by radionucleotide angiogram or echocardiogram.
• Adequate pulmonary function by pulmonary function test. For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \>94% on room air.

You may not qualify if:

• Patients with documented uncontrolled infection at the time of study entry are not eligible.
• Pregnancy/Breast-Feeding Females who are pregnant or breast feeding at the time of study entry are not eligible.
• Patients with bridging fibrosis or cirrhosis of the liver.
• Uncontrolled bacterial, viral or fungal infection in the past month.
• Seropositivity for HIV.
• Patients who have received prior hematocrit (HCT) within three months of enrollment for reduced intensity regimen and within six months for myeloablative regimen/reduced toxicity regimens.

Sponsors & Collaborators

• Diane George: lead

Study Sites (1)

Morgan Stanley Children's Hospital, New York-Presbyterian, Columbia University

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Bone Marrow Failure Disorders; Anemia, Aplastic; Neutropenia, Severe Congenital, Autosomal Recessive 3; Anemia, Diamond-Blackfan; Shwachman-Diamond Syndrome; Primary Immunodeficiency Diseases; Acquired Immunodeficiency Syndrome; Histiocytosis; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome; Histiocytosis, Langerhans-Cell; Hemoglobinopathies; Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia; Anemia, Hypoplastic, Congenital; Red-Cell Aplasia, Pure; Congenital Bone Marrow Failure Syndromes; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Exocrine Pancreatic Insufficiency; Pancreatic Diseases; Digestive System Diseases; Lipid Metabolism, Inborn Errors; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipomatosis; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Lymphatic Diseases; Histiocytosis, Non-Langerhans-Cell; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic

Study Officials

• Diane George, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: October 17, 2013
• First Posted: October 21, 2013
• Study Start: March 1, 2013
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): February 1, 2030
• Last Updated: August 14, 2025

Record last verified: 2025-08

Locations

US (1)