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Graft Vs Host DiseaseNCT05968170

TCRαβ/CD19 Depletion of Stem Cell Grafts for Transplant

A study testing CliniMACS® device in people with Graft Vs Host Disease and Graft-versus-host-disease, run by Neena Kapoor, M.D..

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The CliniMACS® device is FDA-approved only for one indication (CD34+ selection). Additional use of this device outside of this indication requires the use of feasibility studies. Read more about this study

Who is it for?
Ages Up to 21 years
What is being tested?
CliniMACS® device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
27 May 2025to 1 Jul 2035
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Written informed consent (and written assent, if applicable) obtained prior to enrollment.
  • Age < 21.
  • Lansky Play-Performance Scale or Karnofsky Index score ≥ 60%.
  • Adequate organ function (within 4 weeks of initiation of preparative regimen) as evaluated per institutional guidelines. Adequate major organ system function as demonstrated by:
  • Renal: Creatinine clearance or GFR of ≥ 60mL/min/1.73m2.
  • Hepatic: total bilirubin < 2 mg/dL (unless due to Gilbert syndrome) and ALT/AST ≤ 2.5 times the upper limit of normal.
Show all 10Show fewer
  • Cardiac: LVEF at rest ≥ 50% or SF ≥ 27% (by MUGA or ECHO).
  • Pulmonary: DLCO, FEV1, and FVC ≥ 50% of predicted corrected for hemoglobin. For patients < 7 years of age or those unable to perform PFTs: O2 Sat ˃ 92% on room air by pulse oximetry and on no supplemental O2 at rest.
  • Available donor (matched/mismatched unrelated, mismatched related, related haploidentical) who is healthy and willing to donate peripheral blood stem cells.
  • Patients that have been diagnosed with graft rejection/failure or relapse may be eligible to receive a second transplant pending patient status.

Who cannot join

  • Patients with HIV or uncontrolled fungal, bacterial, or viral infections.
  • Patients with active CNS leukemia or any other active site of extramedullary disease at the time of enrollment.
  • Recipient with HLA antibody against donor.
  • Patients that are pregnant, breastfeeding or unwilling to practice birth control during participation of the study.
  • Any condition that, in the opinion of the Sponsor-Investigator, would compromise the safety of the participant, prevent study participation, or interfere with the evaluation of study endpoints.

About this study

Official title: A Feasibility Study Using the CliniMACS® Device for T-Cell Receptor (TCR) αβ+CD3+/CD19+ Depleted Hematopoietic Stem Cells for Patients Undergoing Transplant

The CliniMACS® device is FDA-approved only for one indication (CD34+ selection). Additional use of this device outside of this indication requires the use of feasibility studies.

Children, adolescents and young adults with malignant and non-malignant conditions undergoing hematopoietic stem cell transplants will have stem cells selected using alpha-beta+/CD19+ cell depletion. This is a single arm feasibility study using this processing of peripheral stem cells with alternative donor sources (haploidentical, mismatched, matched unrelated) to determine efficacy as seen by engraftment and graft-versus-host disease (GVHD).

Read the detailed description

Hematopoietic stem cell transplantation (HSCT) is recognized as an effective cure for a wide range of diagnoses including hematologic malignancies, bone marrow failure syndromes, red blood cell disorders (sickle cell, beta thalassemia), white blood cell disorders (CGD), and immune deficiency disorders. Current therapy with allogeneic HCT from HLA-matched sibling donors has shown to be a potentially curative option for children with high-risk and/or relapsed hematologic malignancies (ALL/AML) as well as primary immune deficiency disorders (PID), however only 25-30% of patients have an HLA-identical matched sibling. Alternative stem cell sources include matched unrelated donors (MUD) and unrelated cord blood (UCB), however, the likelihood of finding an unrelated match can range between 29-79% depending on the patient's ethnic background. Since 2015, the CHLA Transplant and Cellular Therapy Program has performed approximately 90 ex vivo processed haploidentical transplants. Greater than 80% of our patients belong to racial/ethnic groups with limited unrelated donor availability, relying heavily on haploidentical donors. This lack of matched stem cells represents a significant access disparity for underrepresented minorities with life-threatening hematologic or immunologic conditions to undergo a potentially curative HSCT.

The FDA approved the use of the CliniMACS CD34+ Reagent System as a Humanitarian Use Device for the prevention of GVHD in patients with acute myeloid leukemia (AML) in first complete remission undergoing allogeneic hematopoietic stem cell transplantation (HSCT) from a matched related donor. The CliniMACS CD34+ Reagent System decreases the risk of developing GVHD by efficiently removing donor T-cells from the graft prior to infusion by enriching CD34+ blood stem cells, which help to repopulate the patient's immune system. FDA approval was based on data from a phase II, single-arm, multi-center study conducted by the Blood and Marrow Transplant Clinical Trials Network that showed after an intensive myeloablative conditioning, receiving a stem cell transplant from a matched related donor processed through the CliniMACS CD34+ Reagent System as a GVHD prophylaxis led to a low incidence of chronic GVHD, about 19% at 2 years post-transplant. However, removal of all cells except CD34+ selected complicates immune recovery (delay in CD4+ cells) leading to higher rates of opportunistic viral infections and transplant-related mortality.

The use of CD34+ selected processing has facilitated approximately 42 HSCTs in combination of TCRαβ+/CD19 depletion at CHLA. The new approach to ex vivo processing utilizes negative depletion of cells thought to be responsible for the development of aGVHD, αβ TCR positive T-cells and includes simultaneous depletion of CD19+ B-cells. Since 2015, CHLA has conducted TCRαβ/CD19+ depleted HSCTs successfully on several protocols, including the ONC1401 KIR Study (IDE#16412).

Being tested
CliniMACS® device
Keywords
Reduce Graft Vs Host Disease, Transplant, Depletion of Stem Cell Grafts
Medical subject headings
Graft vs Host Disease, Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CliniMACS® deviceDevice

    Also called CliniMACS® CD19 reagent system, CliniMACS® depletion tubing set, CliniMACS® TCR α/β reagent system

    CliniMACS TCR αβ+/CD19+ cell depletion for related or unrelated haploidentical/mismatched/matched hematopoietic stem cell transplant patients and/or high risk GVHD patients.

Study groups in NCT05968170
Study groupRoleWhat they receive
Patients receiving allogeneic hematopoietic stem cell transplantsExperimentalThe test product is an αβ+/CD19+ T-cell depleted stem cell product using the CliniMACS system. The test product is given intravenously over a period of time as dictated by the final volume of the infused product (5mL/kg/hour). The target dose of CD34+ cells is 20-40 x 10^6/kg, but a minimum of 5 x 10^6/kg is required. The target dose of TCRαβ+ T-cells and CD19+/CD20+ T-cells is ≤ 1 x 10^5/kg.
Receives: Device: CliniMACS® device

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of grade 3-4 acute and/or chronic GVHD at Day+100

    Assess the cumulative incidence of severe GVHD following HSCT with TCRαβ+/CD19+ T-cell depleted grafts, as determined by the presence of Grade III-IV aGVHD and/or cGVHD by Day+100 post-HSCT.

    Measured: Day+100 post-HSCT

Secondary outcomes (3)
  1. Incidence of engraftment at Day+30.

    Assess the efficacy of TCRαβ+/CD19+ T-cell depleted HSCTs as measured by the engraftment of donor cells by Day+30 post-HSCT.

    Measured: Day+30 post-HSCT

  2. Incidence of transplant-related mortality at 1-year post-HSCT.

    Assess the efficacy of TCRαβ+/CD19+ T-cell depleted HSCTs as measured by the incidence of transplant-related mortality at 1-year post-HSCT.

    Measured: 1-Year post-HSCT

  3. Incidence of T-cell reconstitution at Day+180 (CD4+ T-cell count > 200 and proliferation to PHA > 50% control).

    Assess the immune reconstitution following TCRαβ+/CD19+ T-cell depleted HSCTs as measured by the presence of expanded T-cell numbers and function at Day+180 post-HSCT(CD4+ T-cell count > 200 and proliferation to PHA > 50% control).

    Measured: Day+180 post-HSCT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Aug 2023
  2. Study start27 May 2025 (estimated)
  3. Primary completion27 May 2028 (estimated)
  4. Study completion1 Jul 2035 (estimated)

Why it stopped: No funding available.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05968170
Sponsor's protocol ID
CHLA-23-00327
Other IDs
NCI-2024-07368
Status last verified
Jul 2025
First submitted
18 Apr 2022
Last updated
14 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
Yes: The data will be made available internally to other sub-investigators that have expressed interest. Data that will be shared must go through the Sponsor-Investigator and will be redacted (if not already done) prior to receiving the data so that no identifying information is present.

Publications

  • Oliansky DM, Rizzo JD, Aplan PD, Arceci RJ, Leone L, Ravindranath Y, Sanders JE, Smith FO 3rd, Wilmot F, McCarthy PL Jr, Hahn T. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute myeloid leukemia in children: an evidence-based review. Biol Blood Marrow Transplant. 2007 Jan;13(1):1-25. doi: 10.1016/j.bbmt.2006.10.024.

    PubMed 17222748
  • Oliansky DM, Camitta B, Gaynon P, Nieder ML, Parsons SK, Pulsipher MA, Dillon H, Ratko TA, Wall D, McCarthy PL Jr, Hahn T; American Society for Blood and Marrow Transplantation. Role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of pediatric acute lymphoblastic leukemia: update of the 2005 evidence-based review. Biol Blood Marrow Transplant. 2012 Apr;18(4):505-22. doi: 10.1016/j.bbmt.2011.12.585. Epub 2011 Dec 29.

    PubMed 22209888
  • Leung W, Campana D, Yang J, Pei D, Coustan-Smith E, Gan K, Rubnitz JE, Sandlund JT, Ribeiro RC, Srinivasan A, Hartford C, Triplett BM, Dallas M, Pillai A, Handgretinger R, Laver JH, Pui CH. High success rate of hematopoietic cell transplantation regardless of donor source in children with very high-risk leukemia. Blood. 2011 Jul 14;118(2):223-30. doi: 10.1182/blood-2011-01-333070. Epub 2011 May 25.

    PubMed 21613256
  • Fuchs EJ. Haploidentical transplantation for hematologic malignancies: where do we stand? Hematology Am Soc Hematol Educ Program. 2012;2012:230-6. doi: 10.1182/asheducation-2012.1.230.

    PubMed 23233586
  • Zeidan AM, Forde PM, Symons H, Chen A, Smith BD, Pratz K, Carraway H, Gladstone DE, Fuchs EJ, Luznik L, Jones RJ, Bolanos-Meade J. HLA-haploidentical donor lymphocyte infusions for patients with relapsed hematologic malignancies after related HLA-haploidentical bone marrow transplantation. Biol Blood Marrow Transplant. 2014 Mar;20(3):314-8. doi: 10.1016/j.bbmt.2013.11.020. Epub 2013 Dec 1.

    PubMed 24296490
  • Food and Drug Administration, HHS. Eligibility determination for donors of human cells, tissues, and cellular and tissue-based products. Final rule. Fed Regist. 2004 May 25;69(101):29785-834.

    PubMed 15160713
  • Food and Drug Administration, HHS. Current good tissue practice for human cell, tissue, and cellular and tissue-based product establishments; inspection and enforcement. Final rule. Fed Regist. 2004 Nov 24;69(226):68611-88.

    PubMed 15562555
  • Abdelhakim H, Abdel-Azim H, Saad A. Role of alphabeta T Cell Depletion in Prevention of Graft versus Host Disease. Biomedicines. 2017 Jun 26;5(3):35. doi: 10.3390/biomedicines5030035.

    PubMed 28672883
  • Radestad E, Sundin M, Torlen J, Thunberg S, Onfelt B, Ljungman P, Watz E, Mattsson J, Uhlin M. Individualization of Hematopoietic Stem Cell Transplantation Using Alpha/Beta T-Cell Depletion. Front Immunol. 2019 Feb 11;10:189. doi: 10.3389/fimmu.2019.00189. eCollection 2019.

    PubMed 30804948
  • Ciurea SO, Bayraktar UD. "No donor"? Consider a haploidentical transplant. Blood Rev. 2015 Mar;29(2):63-70. doi: 10.1016/j.blre.2014.09.009. Epub 2014 Sep 30.

    PubMed 25307958
  • Gournay V, Dumas G, Lavillegrand JR, Hariri G, Urbina T, Baudel JL, Ait-Oufella H, Maury E, Brissot E, Legrand O, Malard F, Mohty M, Guidet B, Dulery R, Bige N. Outcome of allogeneic hematopoietic stem cell transplant recipients admitted to the intensive care unit with a focus on haploidentical graft and sequential conditioning regimen: results of a retrospective study. Ann Hematol. 2021 Nov;100(11):2787-2797. doi: 10.1007/s00277-021-04640-7. Epub 2021 Sep 3.

    PubMed 34476574
  • Giardino S, Bagnasco F, Falco M, Miano M, Pierri F, Risso M, Terranova P, Di Martino D, Massaccesi E, Ricci M, Chianucci B, Dell'Orso G, Sabatini F, Podesta M, Lanino E, Faraci M. Haploidentical Stem Cell Transplantation After TCR-alphabeta+ and CD19+ Cells Depletion In Children With Congenital Non-Malignant Disease. Transplant Cell Ther. 2022 Jul;28(7):394.e1-394.e9. doi: 10.1016/j.jtct.2022.04.002. Epub 2022 Apr 8.

    PubMed 35405368
  • Arnold DE, MacMath D, Seif AE, Heimall JR, Wang Y, Monos D, Grupp SA, Bunin NJ. Immune Reconstitution Following TCRalphabeta/CD19-Depleted Hematopoietic Cell Transplantation for Hematologic Malignancy in Pediatric Patients. Transplant Cell Ther. 2021 Feb;27(2):169.e1-169.e9. doi: 10.1016/j.jtct.2020.10.006. Epub 2020 Dec 10.

    PubMed 33830028
  • Mitchell R, Cole T, Shaw PJ, Mechinaud F, O'Brien T, Fraser C. TCR alpha+ beta+ /CD19+ cell-depleted hematopoietic stem cell transplantation for pediatric patients. Pediatr Transplant. 2019 Sep;23(6):e13517. doi: 10.1111/petr.13517. Epub 2019 Jul 4.

    PubMed 31271477
  • Bethge WA, Eyrich M, Mielke S, Meisel R, Niederwieser D, Schlegel PG, Schulz A, Greil J, Bunjes D, Brecht A, Kuball J, Schumm M, Vucinic V, Wiesneth M, Bonig H, Westinga K, Biedermann S, Holtkamp S, Karitzky S, Malchow M, Siewert C, Handgretinger R, Lang P. Results of a multicenter phase I/II trial of TCRalphabeta and CD19-depleted haploidentical hematopoietic stem cell transplantation for adult and pediatric patients. Bone Marrow Transplant. 2022 Mar;57(3):423-430. doi: 10.1038/s41409-021-01551-z. Epub 2021 Dec 24.

    PubMed 34952929

Questions about this trial

What is this clinical trial studying?

A study testing CliniMACS® device in people with Graft Vs Host Disease and Graft-versus-host-disease, run by Neena Kapoor, M.D..

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 14 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of grade 3-4 acute and/or chronic GVHD at Day+100 (time frame: Day+100 post-HSCT). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05968170, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2025.

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