CD34+ Stem Cell Selection for Patients Receiving a Matched or Partially Matched Family or Unrelated Adult Donor Allogeneic Stem Cell Transplantation for Non-Malignant Disease
CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation
Sponsors
Source
Columbia University
Oversight Info
Has Dmc
Yes
Is Fda Regulated Drug
Yes
Is Fda Regulated Device
No
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.
Detailed Description
Graft-versus-host disease (GVHD) is a condition that results from a reaction of transplanted
donor T-lymphocytes against the body and organs of the patient receiving the transplanted
cells. There are two forms: acute (early) and chronic (late). Acute GVHD may produce skin
rashes, liver disease, diarrhea, and an increased risk of infection. Chronic GVHD can appear
in patients without prior acute GVHD. Chronic GVHD may also produce skin rashes, liver
disease, diarrhea and an increased risk of infection. GVHD can make patients very sick, and
have GVHD can make it more likely that patients will not survive their transplant. In this
study, the investigators are offering to treat the donor peripheral blood stem cells in the
hope that it will make it less likely for the patient who receives them from having GVHD.
Patients on this study are being offered an experimental treatment involving the use of the
CliniMACS® Reagent System (Miltenyi Biotec, Germany), a CD34+ selection device to remove
T-cells from the peripheral blood stem cell transplant in order to decrease the risk of acute
and chronic GVHD. CD34+ stem cells are selected from the donor's peripheral blood stem cells.
In doing this, T-cells are also removed. T-cells are the cells which are responsible for
graft versus host disease (GVHD). This study is a clinical trial for patients diagnosed with
a non-malignant disease who will receive a peripheral blood stem cell transplant. Patients
with the following types of non-malignant diseases can participate in this study: Bone marrow
failure syndromes (including Severe Aplastic Anemia, Severe Congenital Neutropenia,
Amegakaryocytic Thrombocytopenia (Kostmann's Syndrome), Diamond-Blackfan Anemia, Schwachman
Diamond Syndrome, Primary Immunodeficiency Syndromes, Acquired Immunodeficiency Syndromes,
and Histiocytic Disorders) and Hemoglobinopathies (including Sickle Cell Anemia and
Sickle/Beta Thalassemia). Patients on this study will be given standard transplant therapy
with either high doses of chemotherapy drugs or lower doses of chemotherapy drugs, depending
on their disease. Diseases within each disease group will receive chemotherapy that is
standard for that condition.
Some patients on this study will receive an allogeneic stem cell transplant (AlloSCT) from a
matched related donor. If a patient does not have a matched related donor, a bone marrow
search will be done at all of the bone marrow banks in the world. The patient will then go on
to receive an AlloSCT from either a partially matched family member or an unrelated adult
stem cell transplant donor. The transplanted cells will allow all the normal parts of the
patient's blood system to recover. The experimental portion of this treatment involves the
use of a Miltenyi CliniMACS CD34+ selection device to remove T-cells from the peripheral
blood stem cell transplant in order to decrease the risk of acute and chronic GVHD. CD34+
stem cell selection AlloSCT has been studied in adults with the malignant and non-malignant
disease with successful engraftment and has shown some improvement in GVHD. It is unknown if
CD34+ stem cell selection will work to prevent severe GVHD in children and adolescents.
Overall Status
Recruiting
Start Date
2013-03-01
Completion Date
2019-12-01
Primary Completion Date
2019-12-01
Phase
Early Phase 1
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
|
Incidence of acute graft versus host disease (GVHD) |
100 days |
Secondary Outcome
Measure |
Time Frame |
|
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 |
|
Incidence of secondary graft failure |
1 year |
Enrollment
25
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
, 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 Intervention
Intervention Type
Biological
Intervention Name
Description
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).
Arm Group Label
CliniMACS PLUS followed by chemotherapy
Eligibility
Criteria
Inclusion Criteria:
- 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.
- Additional eligibility for patients with non-malignant disorders receiving reduced
intensity conditioning
- Adequate renal function as determined by the institutional normal range.
- Adequate liver function per protocol.
- Adequate cardiac function per protocol.
- Adequate pulmonary function per protocol.
Exclusion Criteria:
- 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.
-- The following additional exclusion criteria for patients with sickle cell anemia
the following exclusion criteria also apply
- 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.
Gender
All
Minimum Age
N/A
Maximum Age
40 Years
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
Diane George, MD |
Principal Investigator |
Columbia University |
Overall Contact
Location
Facility |
Status |
Contact |
Investigator |
|
Morgan Stanley Children's Hospital, New York-Presbyterian, Columbia University New York New York 10032 United States |
Recruiting |
Last Name: Diane George, MD Role: Principal Investigator |
Location Countries
Country
United States
Verification Date
2019-03-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor-Investigator
Investigator Affiliation
Columbia University
Investigator Full Name
Diane George, MD
Investigator Title
Assistanct Professor of Pediatrics
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
, 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 Has Expanded Access
No
Condition Browse
Acquired Immunodeficiency Syndrome , HIV Infections , Histiocytosis, Langerhans-Cell , Anemia , Anemia, Sickle Cell , Thrombocytopenia , Thalassemia , Neutropenia , Anemia, Aplastic , beta-Thalassemia , Histiocytosis , Hemoglobinopathies , Pancytopenia , Anemia, Diamond-Blackfan , Lymphocytosis , Lymphohistiocytosis, Hemophagocytic , Immunologic Deficiency Syndromes , Macrophage Activation Syndrome , Syndrome
, HIV Infections , Histiocytosis, Langerhans-Cell , Anemia , Anemia, Sickle Cell , Thrombocytopenia , Thalassemia , Neutropenia , Anemia, Aplastic , beta-Thalassemia , Histiocytosis , Hemoglobinopathies , Pancytopenia , Anemia, Diamond-Blackfan , Lymphocytosis , Lymphohistiocytosis, Hemophagocytic , Immunologic Deficiency Syndromes , Macrophage Activation Syndrome , Syndrome Number Of Arms
1
Arm Group
Arm Group Label
CliniMACS PLUS followed by chemotherapy
Arm Group Type
Experimental
Description
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).
Firstreceived Results Date
N/A
Overall Contact Backup
Patient Data
Sharing Ipd
Undecided
Firstreceived Results Disposition Date
N/A
Study Design Info
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Study First Submitted
October 17, 2013
Study First Submitted Qc
October 17, 2013
Study First Posted
October 21, 2013
Last Update Submitted
March 12, 2019
Last Update Submitted Qc
March 12, 2019
Last Update Posted
March 14, 2019
ClinicalTrials.gov processed this data on December 05, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.