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

NCT02061800 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: AAAK8060
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Chronic Myeloid Leukemia (CML); Acute Myelogenous Leukemia (AML); Myelodysplastic Syndrome (MDS); Juvenile Myelomonocytic Leukemia (JMML); Acute Lymphoblastic Leukemia (ALL); Lymphoma (Hodgkin's and Non-Hodgkin's)

Keywords

Unrelated donor transplant; Allogenic Stem Cell Transplant; Adult Bone Marrow Transplant; Pediatric Bone Marrow Transplant; Related donor transplant; Haploidentical donor transplant; Peripheral blood stem cell transplantation; Non-malignant disease; 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; Reduced-Intensity Conditioning; Sickle Cell Disease; Sickle Cell-beta-thalassemia

Outcome Measures

Primary Outcomes (1)

• Incidence of acute GVHD

  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)

  Up to 2 years post-transplant

Secondary Outcomes (9)

• Time to neutrophil engraftment

  Up to 1 year post-transplant

• Time to immune reconstitution

  Up to 2 years post-transplant

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

  Up to 100 days post-transplant

• Time to platelet engraftment

  Up to 1 year post-transplant

• Incidence of chronic GVHD

  Up to 2 years post-transplant

Study Arms (3)

Full intensity with TBI

ACTIVE COMPARATOR

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.

Device: CliniMACS CD34+ Reagent System; Drug: Thiotepa; Drug: Cyclophosphamide; Drug: Alemtuzumab; Drug: Tacrolimus; Drug: Methylprednisolone

Full intensity without TBI

EXPERIMENTAL

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.

Device: CliniMACS CD34+ Reagent System; Drug: Alemtuzumab; Drug: Tacrolimus; Drug: Melphalan; Drug: Busulfan; Drug: Methylprednisolone

Reduced intensity

EXPERIMENTAL

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.

Device: CliniMACS CD34+ Reagent System; Drug: Alemtuzumab; Drug: Tacrolimus; Drug: Busulfan; Drug: Fludarabine; Drug: Methylprednisolone

Interventions

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.

Full intensity with TBI; Full intensity without TBI; Reduced intensity

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.

Also known as: Thioplex

Full intensity with TBI

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.

Also known as: Cytoxan

Full intensity with TBI

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.

Also known as: Campath

Full intensity with TBI; Full intensity without TBI; Reduced intensity

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

Also known as: Prograf, FK506

Full intensity with TBI; Full intensity without TBI; Reduced intensity

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.

Also known as: Alkeran

Full intensity without TBI

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.

Also known as: Busulfex

Full intensity without TBI; Reduced intensity

Fludarabine DRUG

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

Also known as: Fludara

Reduced intensity

Methylprednisolone DRUG

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

Also known as: Solu-Medrol

Full intensity with TBI; Full intensity without TBI; Reduced intensity

Eligibility Criteria

• Age: Up to 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Diane George: lead

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Juvenile; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma; 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

Interventions

Thiotepa; Cyclophosphamide; Alemtuzumab; Tacrolimus; Melphalan; Busulfan; fludarabine; fludarabine phosphate; Methylprednisolone; Methylprednisolone Hemisuccinate

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System 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; 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; Histiocytosis, Non-Langerhans-Cell; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic

Intervention Hierarchy (Ancestors)

Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Diane George, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics, Department of Pediatrics Onc/BMT/Hem

Study Record Dates

• First Submitted: February 11, 2014
• First Posted: February 13, 2014
• Study Start: June 3, 2013
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: June 4, 2024

Record last verified: 2024-06

Locations

US (1)