Ex Vivo T-Cell Depletion of Mobilized Peripheral Blood Stem Cells Via CD34-Selection (EXCESS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Baylor College of Medicine
Sponsor:
Collaborators:
Texas Children's Hospital
The Methodist Hospital System
Center for Cell and Gene Therapy, Baylor College of Medicine
Information provided by (Responsible Party):
Robert Krance, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01189786
First received: August 25, 2010
Last updated: June 25, 2014
Last verified: June 2014
  Purpose

Participants are being asked to take part in this study because treatment of his or her disease requires a stem cell transplant. Stem cells or "mother" cells are the source of normal blood cells and lead to recovery of blood counts after bone marrow transplantation. Unfortunately, there is not a perfectly matched stem cell donor (like a sister or brother) for the participant and his or her disease does not permit enough time to identify another donor (like someone from a registry list that is not his or her relative) or another suitable donor has not been identified. However, a close relative of the patient has been identified whose stem cells are not a perfect match, but can be used.

Alternatively, the patient may have already received a stem cell transplant but have evidence of mixed chimerism, which means some of the patient's own bone marrow cells are present, rather than all of the donor's cells. This may lead to an increased risk of the disease coming back. Or, the patient may have all donor cells but his or her bone marrow is not working very well, which may lead to frequent blood or platelet (cells that help in clotting blood) transfusions or infection.

Regardless of the reason, it may be necessary to isolate stem cells from a haploidentical (half-match) donor in order to provide bone marrow function. Because the stem cells from the donor are only half-matched to the participant, the risk of graft-versus-host disease (GvHD) is very high. GvHD is a complication after transplant caused by donor T cells (graft) that attack the transplant recipient, and this complication can cause death after transplant. Thus, it is important that the donor's blood cells are treated to minimize cells that are most likely to attack the host's tissues. This is done by using a special device to capture the CD34+ stem cells from the donor's stem cell product prior to giving the cells to the host. This method minimizes the donor T cells, which are responsible for causing GvHD.

Purpose: In an effort to lower the occurrences and severity of graft-versus-host disease in patients and to lower the rate of transplant failure, investigators would like to specially treat the donor's blood cells to minimize the cells that are most likely to attack the patient's tissues.


Condition Intervention
Stem Cell Transplant
Allogeneic
Device: CliniMACS CD34 Reagent system

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Ex Vivo T-Cell Depletion of Mobilized Peripheral Blood Stem Cells Via CD34-Selection (EXCESS)

Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • The total incidence of overall acute GvHD (greater than or equal to grade 3) [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
    For both Cohorts, the overall incidence of acute GvHD will be measured 100 days post stem cell transplant. The regimen will be considered acceptable if aGvHD greater than or equal to grade 3 rate is at least 10% or lower.

  • For Cohort 1 only: the rate of primary engraftment 100 days post SCT [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
    Primary engraftment is defined as achievement of absolute neutrophil count (ANC) is greater than or equal to 500/ul for three consecutive days by day 50 post transplant. The treatment regimen will be considered clinically useful if the primary engraftment rate is at least 85%.


Estimated Enrollment: 74
Study Start Date: October 2010
Estimated Study Completion Date: November 2021
Estimated Primary Completion Date: October 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 2: CD34+ cells as a top off
Cohort 2 consists of patients needing additional CD34+ stem cells collected by 'CliniMACS CD34 Reagent system' as a "topoff" without the need for additional conditioning prior to the infusion. These patients who have already received SCT and are receiving CD34+ cells from their original donor for poor graft function, declining chimerism or disease relapse.
Device: CliniMACS CD34 Reagent system
A special machine that separates out the donor cells that have been mixed with a special protein, CD34 antibody, that binds to the stem cells from the white blood cells.
Experimental: Cohort 1: CD34+ Cells for transplant
Cohort 1 consists of patients receiving CD34+ selected peripheral blood stem cell transplant with a preceding conditioning regimen (chemotherapy with, or without, radiation). The stem cells will then be separated out from the white blood cells by a special machine- called a CliniMACS CD34 Reagent System in the laboratory.
Device: CliniMACS CD34 Reagent system
A special machine that separates out the donor cells that have been mixed with a special protein, CD34 antibody, that binds to the stem cells from the white blood cells.

Detailed Description:

Participation in this project will last approximately one year with follow-up exams.

Before treatment can begin, stem cells will be collected from the donor (a close relative) that has been selected as the best match for the participant. White blood cells will be collected from the donor. The cells will then be mixed with a special protein, called a CD34 antibody, that binds to the stem cells, which will then be separated out from the white blood cells by a special machine- called a CliniMACS CD34 Reagent System in the laboratory. This is an investigational device that is not approved by the FDA. Although this device is not approved for use in this country, it has been in use for years and is approved in other countries. The stem cells will be collected and frozen before they will be given to the participant.

On about days 28, 100 and 365 after the transplant, the participant will have the same tests/evaluations since the time of transplant; however, the participant will also have a bone marrow aspirate. This is where samples of bone marrow are taken to evaluate the participant's disease and Graft vs. Host Disease (GvHD) status. For patients who do not develop GvHD, they may have an additional bone marrow aspirate about a year after transplant.

In addition, for purposes of the study, health-related information will be collected for a year from the time of stem cell infusion. This will be used to determine survival, relapse, infections and GvHD that may occur following transplant.

  Eligibility

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria: for Stem Cell Transplant WITH Conditioning (COHORT 1)

The following must be answered YES for a patient to eligible to participate in study:

  • Patient requiring allogeneic SCT
  • Age between birth and 70 years
  • Patient and/or responsible person able to understand and sign consent

Exclusion criteria: for Stem Cell Transplant WITH Conditioning (COHORT 1)

The following must be answered NO for a patient to be eligible to participate in study:

  • Active, acute GvHD > grade II or extensive, chronic GvHD
  • Severe life, threatening infection
  • Pulmonary dysfunction (FEV1, FVC or DLCO 40% of predicted or 3 SD below normal)
  • Cardiac dysfunction (LVSF less than 25%)
  • Psychiatric disturbance
  • Lansky or Karnofsky score < 50%
  • The presence of severe hepatic disease (direct bilirubin >3x upper limit of normal and AST > 5x upper limit of normal)
  • Creatinine > 3x normal
  • Known HIV Positivity
  • Pregnancy

Inclusion Criteria: for CD34+ Topoff WITHOUT conditioning (COHORT 2)

The following must be answered YES for a patient to be eligible to participate in study:

  • Allogeneic SCT Recipient requiring additional cellular therapy
  • Age between birth and 70 years
  • Patient and/or responsible person able to understand and sign consent
  • At least ONE of the following must be answered YES for a patient to be eligible to receive CD34+ topoff:
  • Evidence of mixed chimerisms (less than 95% donor cells)
  • Evidence of of poor bone marrow function (bone marrow cellularity less than 50% with at least one cytopenia)
  • Relapsed disease

Exclusion criteria: for CD34+ Topoff WITHOUT conditioning (COHORT 2)

The following must be answered NO for a patient to be eligible to participate in study:

  • Active, acute GvHD > grade II or extensive, chronic GvHD
  • Severe life, threatening infection

Note: Patients on a clinical treatment protocol, such as MOHEL or HIMSUM are still eligible to receive CD34+ stem cells on this protocol.

  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: NCT01189786

Contacts
Contact: Robert Krance, MD 832-824-4661 rakrance@txch.org
Contact: Marlen Dinu 832-824-4881 mxdinu@txch.org

Locations
United States, Texas
Houston Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Robert Krance, MD    832-824-4661    rakrance@txch.org   
Contact: Marlen Dinu    832-824-4881    mxdinu@txch.org   
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Robert Krance, MD    832-824-4661    rakrance@txch.org   
Contact: Marlen Dinu    832-824-4881    mxdinu@txch.org   
Sponsors and Collaborators
Baylor College of Medicine
Texas Children's Hospital
The Methodist Hospital System
Center for Cell and Gene Therapy, Baylor College of Medicine
Investigators
Principal Investigator: Robert Krance, MD Texas Children's Hospital
  More Information

No publications provided

Responsible Party: Robert Krance, Professor of Pediatrics-Hem-Onc Cell & Gene, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01189786     History of Changes
Other Study ID Numbers: 27251-EXCESS, EXCESS
Study First Received: August 25, 2010
Last Updated: June 25, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:
Haploidentical Stem Cell Transplant
CD34+ Selection
CliniMACS CD34 Reagent system

ClinicalTrials.gov processed this record on July 22, 2014