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Active, Not Recruiting

NCT Number: NCT02061800

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

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).

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Chronic Myeloid Leukemia (CML) Acquired Immunodeficiency Syndrome Acute Lymphoblastic Leukemia (ALL) Acute Myelogenous Leukemia (AML) Anemia Anemia, Aplastic Anemia, Diamond-Blackfan Anemia, Hemolytic Anemia, Hemolytic, Congenital Anemia, Hypoplastic, Congenital Anemia, Sickle Cell Blood-Borne Infections Bone Marrow Diseases Bone Marrow Failure Disorders Chronic Disease Communicable Diseases Congenital Bone Marrow Failure Syndromes Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Disease Attributes Exocrine Pancreatic Insufficiency Genetic Diseases, Inborn Genital Diseases HIV Infections Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies Histiocytosis Histiocytosis, Langerhans-Cell Histiocytosis, Non-Langerhans-Cell Immune System Diseases Immunologic Deficiency Syndromes Immunoproliferative Disorders Infections Juvenile Myelomonocytic Leukemia (JMML) Lentivirus Infections Leukemia Leukemia, Lymphoid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid Leukemia, Myeloid, Acute Leukemia, Myelomonocytic, Juvenile Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Lipomatosis Lung Diseases Lung Diseases, Interstitial Lymphatic Diseases Lymphohistiocytosis, Hemophagocytic Lymphoma Lymphoma (Hodgkin's and Non-Hodgkin's) Lymphoproliferative Disorders Macrophage Activation Syndrome Metabolic Diseases Myelodysplastic Syndrome (MDS) Myelodysplastic Syndromes Myelodysplastic-Myeloproliferative Diseases Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Neutropenia, Severe Congenital, Autosomal Recessive 3 Nutritional and Metabolic Diseases Pancreatic Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Precursor Cell Lymphoblastic Leukemia-Lymphoma Primary Immunodeficiency Diseases RNA Virus Infections Red-Cell Aplasia, Pure Respiratory Tract Diseases Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Shwachman-Diamond Syndrome Slow Virus Diseases Urogenital Diseases Virus Diseases

Age range

Up to 22 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Columbia University Irving Medical Center

New York, 10032, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

General Eligibility (All Patients)

  • Must be < 22 years of age
  • Diagnosed with a malignant disease
  • 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
  • For unrelated donor: A human leukocyte antigen (HLA) 8/10, 9/10 or 10/10 matched unrelated adult donor (MUD) will be required for study entry
  • For 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
  • Adequate renal function
  • Adequate liver function
  • Adequate cardiac function
  • Adequate pulmonary function

Exclusion criteria

  • Patients with documented uncontrolled infection at the time of study entry are not eligible
  • Females who are pregnant or breast feeding at the time of study entry are not eligible

Treatment and study plan

CliniMACS CD34+ Reagent System

Device

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.

Thiotepa

Drug

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.

Other names: Thioplex

Cyclophosphamide

Drug

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.

Other names: Cytoxan

Alemtuzumab

Drug

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.

Other names: Campath

Tacrolimus

Drug

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

Other names: Prograf, FK506

melphalan

Drug

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.

Other names: Alkeran

busulfan

Drug

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.

Other names: Busulfex

Fludarabine

Drug

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

Other names: Fludara

methylprednisolone

Drug

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

Other names: Solu-Medrol

Primary outcomes

  1. Incidence of acute GVHD

    Time frame: Up to 2 years post-transplant

    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)

Secondary outcomes

  1. Time to neutrophil engraftment

    Time frame: Up to 1 year 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.

  2. Time to immune reconstitution

    Time frame: Up to 2 years post-transplant

    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.

  3. Incidence of infection complications including bacterial, viral, fungal and atypical mycobacterial and other infections

    Time frame: Up to 100 days post-transplant

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

  4. Time to platelet engraftment

    Time frame: Up to 1 year 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.

  5. Incidence of chronic GVHD

    Time frame: Up to 2 years post-transplant

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

  6. Severity of acute GVHD

    Time frame: Up to 2 years post-transplant

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

  7. Severity of chronic GVHD

    Time frame: Up to 2 years post-transplant

    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

  8. Incidence of primary graft failure

    Time frame: 42 (or more) days post-transplant

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

  9. Incidence of secondary graft failure

    Time frame: 42 (or more) days post-transplant

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

Sponsors and collaborators

Lead sponsor

Diane George

Other

Registry information

Official study title

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

Important dates

Study start
2013
Primary completion
2026
Study completion
2026
First posted
Feb 13, 2014
Registry last updated
Jun 4, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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