Back to resultsCD34+ (Malignant) Stem Cell Selection for Patients Receiving Allogenic Stem Cell Transplant
Primary Purpose
Chronic Myeloid Leukemia (CML), Acute Myelogenous Leukemia (AML), Myelodysplastic Syndrome (MDS)
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CliniMACS CD34+ Reagent System
Thiotepa
Cyclophosphamide
Alemtuzumab
Tacrolimus
Melphalan
Busulfan
Fludarabine
Methylprednisolone
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Myeloid Leukemia (CML) focused on measuring 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
Eligibility Criteria
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
Sites / Locations
- Columbia University Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Experimental
Experimental
Arm Label
Full intensity with TBI
Full intensity without TBI
Reduced intensity
Arm Description
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.
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
Time to neutrophil engraftment
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.
Time to immune reconstitution
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.
Incidence of infection complications including bacterial, viral, fungal and atypical mycobacterial and other infections
Will be assessed weekly or more as indicated until 84 or 100 days post-transplant, then as clinically indicated.
Time to platelet engraftment
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.
Incidence of chronic GVHD
Chronic GVHD will be assessed and graded with standard NCI grading criteria.
Severity of acute GVHD
Acute GVHD will be assessed and graded with standard NCI grading criteria.
Severity of chronic GVHD
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
Incidence of primary graft failure
Primary graft rejection is defined as the presence of < 20% donor cells
Incidence of secondary graft failure
The presence of < 20% donor derived hematopoietic cells in peripheral blood
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02061800
Brief Title
CD34+ (Malignant) Stem Cell Selection for Patients Receiving Allogenic Stem Cell Transplant
Official 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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Recruiting
Study Start Date
June 3, 2013 (Actual)
Primary Completion Date
December 2021 (Anticipated)
Study Completion Date
December 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Diane George
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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).
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Full intensity with TBI
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Full intensity without TBI
Arm Type
Experimental
Arm Description
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.
Arm Title
Reduced intensity
Arm Type
Experimental
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
CliniMACS CD34+ Reagent System
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Thiotepa
Other Intervention Name(s)
Thioplex
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Alemtuzumab
Other Intervention Name(s)
Campath
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
Prograf, FK506
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
Alkeran
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
Busulfex
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
Standard of care: Fludarabine will be given IV in 50-100 ml of D5W or 0.9% sodium chloride, over 30 minutes.
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone
Other Intervention Name(s)
Solu-Medrol
Intervention Description
Standard of care: Methylprednisolone will be give IV slow infusion over 15-30 minutes.
Primary Outcome Measure Information:
Title
Incidence of acute GVHD
Description
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)
Time Frame
Up to 2 years post-transplant
Secondary Outcome Measure Information:
Title
Time to neutrophil engraftment
Description
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.
Time Frame
Up to 1 year post-transplant
Title
Time to immune reconstitution
Description
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.
Time Frame
Up to 2 years post-transplant
Title
Incidence of infection complications including bacterial, viral, fungal and atypical mycobacterial and other infections
Description
Will be assessed weekly or more as indicated until 84 or 100 days post-transplant, then as clinically indicated.
Time Frame
Up to 100 days post-transplant
Title
Time to platelet engraftment
Description
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.
Time Frame
Up to 1 year post-transplant
Title
Incidence of chronic GVHD
Description
Chronic GVHD will be assessed and graded with standard NCI grading criteria.
Time Frame
Up to 2 years post-transplant
Title
Severity of acute GVHD
Description
Acute GVHD will be assessed and graded with standard NCI grading criteria.
Time Frame
Up to 2 years post-transplant
Title
Severity of chronic GVHD
Description
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
Time Frame
Up to 2 years post-transplant
Title
Incidence of primary graft failure
Description
Primary graft rejection is defined as the presence of < 20% donor cells
Time Frame
42 (or more) days post-transplant
Title
Incidence of secondary graft failure
Description
The presence of < 20% donor derived hematopoietic cells in peripheral blood
Time Frame
42 (or more) days post-transplant
10. Eligibility
Sex
All
Maximum Age & Unit of Time
22 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jody Campbell, MPA
Email
jc5422@cumc.columbia.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Desmarie Sherwood
Email
ds3851@cumc.columbia.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Diane George, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jody Campbell, MPA
Email
jc5422@cumc.columbia.edu
First Name & Middle Initial & Last Name & Degree
Desmarie Sherwood
Email
ds3851@cumc.columbia.edu
First Name & Middle Initial & Last Name & Degree
Diane George, MD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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CD34+ (Malignant) Stem Cell Selection for Patients Receiving Allogenic Stem Cell Transplant
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