TCRαβ/CD19 Depletion of Stem Cell Grafts for Transplant

NCT05968170 | Withdrawn DMC FDA Device

• 2 other identifiers: CHLA-23-00327NCI-2024-07368
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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. 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).

Conditions

Graft Vs Host Disease; Graft-versus-host-disease; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Non-hematologic Malignancy; Hematologic Malignancy

Keywords

Reduce Graft Vs Host Disease; Transplant; Depletion of Stem Cell Grafts

Outcome Measures

Primary Outcomes (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.

  Day+100 post-HSCT

Secondary Outcomes (3)

• Incidence of engraftment at Day+30.

  Day+30 post-HSCT

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

  1-Year post-HSCT

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

  Day+180 post-HSCT

Other Outcomes (1)

• Incidence of microbial contamination of the infused cells product leading to possible infection in the recipient (i.e., antibiotics needed for > 48 hours).

  Day+30

Study Arms (1)

Patients receiving allogeneic hematopoietic stem cell transplants

EXPERIMENTAL

The 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.

Device: CliniMACS® device

Interventions

CliniMACS® device DEVICE

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

Also known as: CliniMACS® CD19 reagent system, CliniMACS® depletion tubing set, CliniMACS® TCR α/β reagent system

Patients receiving allogeneic hematopoietic stem cell transplants

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Neena Kapoor, M.D.: lead

Related Publications (15)

• 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.

  PMID: 17222748 BACKGROUND

• 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.

  PMID: 22209888 BACKGROUND

• 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.

  PMID: 21613256 BACKGROUND

• 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.

  PMID: 23233586 BACKGROUND

• 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.

  PMID: 24296490 BACKGROUND

• 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.

  PMID: 15160713 BACKGROUND

• 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.

  PMID: 15562555 BACKGROUND

• 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.

  PMID: 28672883 BACKGROUND

• 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.

  PMID: 30804948 BACKGROUND

• 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.

  PMID: 25307958 BACKGROUND

• 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.

  PMID: 34476574 BACKGROUND

• 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.

  PMID: 35405368 BACKGROUND

• 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.

  PMID: 33830028 BACKGROUND

• 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.

  PMID: 31271477 BACKGROUND

• 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.

  PMID: 34952929 BACKGROUND

MeSH Terms

Conditions

Graft vs Host Disease; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Immune System Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site

Study Officials

• Neena Kapoor, MD

  Children's Hospital Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: April 18, 2022
• First Posted: August 1, 2023
• Study Start: May 27, 2025
• Primary Completion (Estimated): May 27, 2028
• Study Completion (Estimated): July 1, 2035
• Last Updated: July 14, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data will be made available upon request by submitting criteria of interest. The Sponsor-Investigator will provide a copy of the data. The copy will be indefinitely available to the interested party.
• Access Criteria: Data will be made available upon request by submitting criteria of interest. A copy of the redacted data will be given. No other party will have access to the database at any time outside of the Sponsor-Investigator and data management/CRC team.