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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief Summary: 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.

Detailed Summary:

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
Sponsor: Diane George, MD

Current Primary Outcome:

  • 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)
  • Incidence 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 years and yearly (366+ days post-transplant)
  • Severity of acute GVHD [ Time Frame: Up to 2 years post-transplant ]
    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 ]
    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 ]

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • 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.
    • 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
    • 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
    • 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


    Original Secondary Outcome: Same as current

    Information By: Columbia University

    Dates:
    Date Received: February 11, 2014
    Date Started: November 2013
    Date Completion: December 2018
    Last Updated: July 26, 2016
    Last Verified: July 2016