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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Columbia University
Sponsor:
Information provided by (Responsible Party):
Diane George, MD, Columbia University
ClinicalTrials.gov Identifier:
NCT02061800
First received: February 11, 2014
Last updated: NA
Last verified: February 2014
History: No changes posted
  Purpose

This study is a research study involving 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) The purpose of this study is to learn more about the effects of 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 a Miltenyi CliniMacs 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.


Condition Intervention Phase
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)
Device: CliniMACS CD34+ Reagent System
Drug: Thiotepa
Drug: Cyclophosphamide
Drug: Alemtuzumab
Drug: Tacrolimus
Drug: Melphalan
Drug: Busulfan
Drug: Fludarabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Incidence of acute GVHD [ Time Frame: Up to 2 years post-transplant ] [ Designated as safety issue: No ]
    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)

  • Incidence of chronic GVHD [ Time Frame: Up to 2 years post-transplant ] [ Designated as safety issue: No ]
    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 years and yearly (366+ days post-transplant)

  • Severity of acute GVHD [ Time Frame: Up to 2 years post-transplant ] [ Designated as safety issue: No ]
    Actue 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)

  • Severity of chronic GVHD [ Time Frame: Up to 2 years post-transplant ] [ Designated as safety issue: No ]
    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 years and yearly (366+ days post-transplant).

  • Incidence of primary graft failure [ Time Frame: 42 (or more) days post-transplant ] [ Designated as safety issue: No ]
    Primary graft rejection is defined as the presence of < 20% donor cells assessed by bone marrow or peripheral blood chimerism assays on day 42 post-transplant. Infusion of a second stem cell product on or prior to day 42 post-transplant will be considered primary graft rejection.

  • Incidence of secondary graft failure [ Time Frame: 42 (or more) days post-transplant ] [ Designated as safety issue: No ]
    The presence of < 20% donor derived hematopoietic cells in peripheral blood or bone marrow after day 42 post-transplant in a patient with prior evidence of > 20% donor cells will be considered late graft rejection. Also, infusion of a second stem cell product beyond day 42 post initial transplant will be considered late graft rejection.


Secondary Outcome Measures:
  • Time to neutrophil engraftment [ Time Frame: Up to 1 year post-transplant ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 2 years post-transplant ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 100 days post-transplant ] [ Designated as safety issue: No ]
    Will be assessed weekly or more as indicated until 84 or 100 days post-transplant, then as clinically indicated

  • Time to platelet engraftment [ Time Frame: Up to 1 year post-transplant ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 25
Study Start Date: November 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Full intensity with Total body irradiation (TBI)
Patients will start their pre-conditioning regimen on 8 days before scheduled transplant. Fractionated total body irradiation (TBI) will be administered twice daily for 3 days 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. GVHD prophylaxis will consist of tacrolimus only. Tacrolimus administration will begin on the day after transplant.
Device: CliniMACS CD34+ Reagent System
The CliniMACS® Reagent System (Miltenyi Biotec, Bergisch Gladbach, 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.
Drug: Thiotepa
Other Name: Thioplex
Drug: Cyclophosphamide
Other Names:
  • Cytoxan
  • CTX
Drug: Alemtuzumab
Other Name: Campath
Drug: Tacrolimus
Other Names:
  • Prograf
  • FK506
Experimental: Full intensity without TBI
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 and GVHD prophylaxis will consist of tacrolimus only. Tacrolimus administration will begin on the day after their transplant.
Device: CliniMACS CD34+ Reagent System
The CliniMACS® Reagent System (Miltenyi Biotec, Bergisch Gladbach, 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.
Drug: Alemtuzumab
Other Name: Campath
Drug: Tacrolimus
Other Names:
  • Prograf
  • FK506
Drug: Melphalan
Other Name: Alkeran
Drug: Busulfan
Other Name: Busulfex
Experimental: Reduced Toxicity

Patients will begin tacrolimus on the first day of conditioning (8 days before scheduled transplant). Patients will receive alemtuzumab on the 3rd-7th day before transplant; busulfan twice daily on the 5th-8th day before transplant; and fludarabine on the 2nd-7th day before transplant. The stem cell infusion will be performed and GVHD prophylaxis will consist of tacrolimus only.

For patients with a prior history of hepatic toxicity and/or high-risk for veno-occlusive disease (VOD) or other liver toxicity post stem cell transplant, melphalan at 70 mg/m2 will be substituted for Busulfan on the 8th and 9th day before transplant, followed by fludarabine on the 2nd-7th day before transplant and alemtuzumab on the 3rd-7th day before transplant. The stem cell infusion will be performed and GVHD prophylaxis will consist of tacrolimus only.

Device: CliniMACS CD34+ Reagent System
The CliniMACS® Reagent System (Miltenyi Biotec, Bergisch Gladbach, 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.
Drug: Alemtuzumab
Other Name: Campath
Drug: Tacrolimus
Other Names:
  • Prograf
  • FK506
Drug: Busulfan
Other Name: Busulfex
Drug: Fludarabine
Other Name: Fludara

Detailed Description:

CD34+ stem cells (the cells that make all the types of blood cells in the body) are selected (removed) from the donor's peripheral blood stem cells. In doing this, T-cells (a type of blood cell) are also removed. T-cells are the cells which are responsible for severe acute and chronic graft versus host disease (GVHD). GVHD is a condition that results from a reaction of the transplanted donor T-lymphocytes (a kind of white blood cell) against the body and organs. 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 also appear in subjects without prior acute GVHD. Chronic GVHD may also produce skin rashes, liver disease, diarrhea and an increased risk of infection. Chronic GVHD may be mild and respond to agents which suppress the immune system, or it could be very severe. It may also last for over a year.

Once this CD34 selection process is complete, the CD34+ stem cell AlloSCT is given to the recipient without most of the T-cells to see if this therapy will lessen the incidence and seriousness of graft versus host disease (GVHD). CD34+ stem cell selection AlloSCT has been studied in adults with malignant and non-malignant disease with successful engraftment and has shown some improvement in GVHD. We do not know if CD34+ stem cell selection will work to prevent severe GVHD in children, adolescents and young adults.

Subjects are being offered this experimental treatment involving 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. There will be about 25 subjects participating in this study at Columbia University Medical Center. The purpose of this study is to learn more about the effects of CD34+ stem cell selection on GVHD in children, adolescents and young adults.

The goals of this study are:

  • To determine how often acute GVHD occurs and how severe the acute GVHD is in the children, adolescents and young adults receiving CD34+ selection of their peripheral blood stem cell transplant from a family member or adult unrelated donor.
  • To determine how often primary graft failure and secondary graft failure occurs in the children, adolescents and young adults receiving a peripheral blood stem cell transplant from a family member or adult unrelated donor.
  • To see how quickly neutrophils (infection fighting white blood cells) will recover following CD34+ selection of their peripheral blood stem cell transplant from a family member or adult unrelated donor.
  • To see if the time for the immune system (the body's defense system) to recover will benefit from receiving CD34+ selection of their peripheral blood stem cell transplant from a family member or adult unrelated donor.
  • To see how often bacterial, viral, fungal and atypical mycobacteria (TB-like) infections will occur in the children, adolescents and young adults receiving CD34+ selection of their peripheral blood stem cell transplant from a family member or adult unrelated donor.

No tests will be performed for research purposes only. All required testing in this protocol is for the purpose of standard of care clinical assessment specific to the subject's disease. The only procedure specific to research will be the selection of CD34+ cells from the donor's peripheral blood stem cells using the Miltenyi Clinimacs CD34+ selection device.

Study specific requirements occur up to 2 years post-transplant, although the study team will collect data on the progress of subjects yearly until termination of the study to observe if subjects are responding to therapy and have no worsening GVHD.

  Eligibility

Ages Eligible for Study:   up to 22 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02061800

Contacts
Contact: Jean Sosna, RN 212-305-2050 js4403@columbia.edu

Locations
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Jean Sosna, RN    212-305-2050      
Principal Investigator: Diane George, MD         
Sponsors and Collaborators
Diane George, MD
Investigators
Principal Investigator: Diane George, MD Columbia University
  More Information

No publications provided

Responsible Party: Diane George, MD, Assistant Professor of Pediatrics, Department of Pediatrics Onc/BMT/Hem, Columbia University
ClinicalTrials.gov Identifier: NCT02061800     History of Changes
Other Study ID Numbers: AAAK8060
Study First Received: February 11, 2014
Last Updated: February 11, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Columbia University:
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

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Myelodysplastic-Myeloproliferative Diseases
Busulfan
Cyclophosphamide
Melphalan
Thiotepa
Fludarabine monophosphate
Tacrolimus
Campath 1G

ClinicalTrials.gov processed this record on July 26, 2014