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

NCT01189786 | Recruiting DMC FDA Device

• 2 other identifiers: H-27251 EXCESSEXCESS
• Study Type: interventional
• Target: 241
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Stem Cell Transplant; Allogeneic

Keywords

Haploidentical Stem Cell Transplant; CD34+ Selection; CliniMACS CD34 Reagent system

Outcome Measures

Primary Outcomes (2)

• For Cohort 1: the rate of primary engraftment 50 days post SCT

  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%.

  50 days

• For Cohort 2 (Without Conditioning) and Cohort 3 (With Conditioning): The total incidence of overall acute GvHD (greater than or equal to grade 3)

  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.

  100 days

Secondary Outcomes (1)

• Assessment of Long Term Survival

  1 year

Study Arms (3)

Cohort 2: CD34+ cells as a top off Without Conditioning

EXPERIMENTAL

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

Cohort 1: CD34+ Cells for transplant

EXPERIMENTAL

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

Cohort 3: CD34+ cells as a top off With Conditioning

EXPERIMENTAL

Cohort 3 consists of patients needing additional CD34+ stem cells collected by 'CliniMACS CD 34+ Reagent System' as a "topoff" with the need for additional conditioning prior to the infusion. These patients who have already received SCT with conditioning and are receiving CD34+ cells from their original donor for poor graft function, declining chimerism or disease relapse.

Device: CliniMACS CD34 Reagent system

Interventions

CliniMACS CD34 Reagent system DEVICE

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.

Cohort 1: CD34+ Cells for transplant; Cohort 2: CD34+ cells as a top off Without Conditioning; Cohort 3: CD34+ cells as a top off With Conditioning

Eligibility Criteria

• Age: Up to 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

Study Officials

• Robert Krance, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Robert Krance, MD

CONTACT

832-824-4661; rakrance@txch.org

Marlen Dinu

CONTACT

832-824-4881; mxdinu@txch.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics-Hem-Onc Cell & Gene

Study Record Dates

• First Submitted: August 25, 2010
• First Posted: August 27, 2010
• Study Start: October 1, 2010
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): November 1, 2027
• Last Updated: December 3, 2025

Record last verified: 2025-11

Locations

US (2)