A Feasibility Study Using CLINIMACS® for Alpha/Beta T-Cell Depletion in Stem Cell Transplant

NCT04337515 | Recruiting FDA Device

• 1 other identifier: 19-28063
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

Patients in need of an allogeneic hematopoietic cell transplant (HCT) are at risk of developing graft-versus-host-disease (GVHD). In certain clinical situations, the optimal approach to minimize the risk of GVHD is to perform ex vivo alpha-beta T-cell depletion of the donor cells. However, the CliniMACS® Device is FDA-approved only for a narrow indication. All other uses of ex vivo processed cells must be done under a feasibility study protocol.

Conditions

Graft Vs Host Disease; Graft-versus-host-disease

Outcome Measures

Primary Outcomes (1)

• 100-day incidence of Grade III-IV acute GVHD

  The cumulative incidence of Grade III-IV acute GVHD at Day 100 will be summarized by incidence curves. GVHD evaluations will be performed using standard criteria.37 Patients with graft rejection will be censored.

  100 days

Secondary Outcomes (5)

• 30-day incidence of engraftment

  30 days

• 1-year incidence of transplant-related mortality

  12 months

• 1-year incidence of systemic steroid-requiring chronic GVHD

  12 months

• 1-year incidence of autoimmunity requiring intervention with immunosuppressive agents as treatment.

  12 months

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

  180 days

Study Arms (1)

Patients receiving allogeneic hematopoietic cell transplant

EXPERIMENTAL

The test product is a stem cell product which has been alpha-beta T- cell depleted using the CliniMACS system. Alpha-beta T-cell depleted cells are given intravenously over a period of time as dictated by the final volume of the infused product (5 ml/kg/hour). The target dose of CD34+ cells is ≥20x10\^6/kg, but a minimum of ≥2.5x10\^6/kg is required. The target dose of T-cell receptor (TCR) alpha-beta CD3+ cells is ≤1x10\^5/kg.

Device: CliniMacs®

Interventions

CliniMacs® DEVICE

CliniMACS® CD34 Reagent System is now indicated for processing hematopoietic progenitor cells collected by apheresis (PBSC) from an allogeneic, HLA-identical MSD to obtain a CD34+ cell-enriched population for hematopoietic reconstitution following a myeloablative preparative regimen without the need for additional GVHD prophylaxis in patients with AML in first morphologic complete remission (CR1).

Also known as: CliniMACS® CD34 Reagent System

Patients receiving allogeneic hematopoietic cell transplant

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or female 0-30 years of age at time of transplant admission
• Documentation of a disease requiring HCT
• A donor (mismatched related or unrelated) must be located who are healthy and willing, and whom are able to donate bone marrow (BM) or peripheral blood stem cells (PBSC). Matched related donors may be used for patients with Fanconi Anemia.
• Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study

You may not qualify if:

• Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data
• Presence of a healthy and willing HLA-identical related donor (except when the patient has Fanconi Anemia).
• Patient with an anticipated life expectancy of \<1 month
• Patients with known hypersensitivity to murine (mouse) proteins or iron dextran

Sponsors & Collaborators

• Christopher Dvorak: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

Related Publications (8)

• 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

• Klein OR, Buddenbaum J, Tucker N, Chen AR, Gamper CJ, Loeb D, Zambidis E, Llosa NJ, Huo JS, Robey N, Holuba MJ, Kasamon YL, McCurdy SR, Ambinder R, Bolanos-Meade J, Luznik L, Fuchs EJ, Jones RJ, Cooke KR, Symons HJ. Nonmyeloablative Haploidentical Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide for Pediatric and Young Adult Patients with High-Risk Hematologic Malignancies. Biol Blood Marrow Transplant. 2017 Feb;23(2):325-332. doi: 10.1016/j.bbmt.2016.11.016. Epub 2016 Nov 22.

  PMID: 27888014 BACKGROUND

• Berger M, Lanino E, Cesaro S, Zecca M, Vassallo E, Faraci M, De Bortoli M, Barat V, Prete A, Fagioli F. Feasibility and Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant High-Dose Cyclophosphamide for Children and Adolescents with Hematologic Malignancies: An AIEOP-GITMO Retrospective Multicenter Study. Biol Blood Marrow Transplant. 2016 May;22(5):902-9. doi: 10.1016/j.bbmt.2016.02.002. Epub 2016 Feb 6.

  PMID: 26860636 BACKGROUND

• Abboud R, Keller J, Slade M, DiPersio JF, Westervelt P, Rettig MP, Meier S, Fehniger TA, Abboud CN, Uy GL, Vij R, Trinkaus KM, Schroeder MA, Romee R. Severe Cytokine-Release Syndrome after T Cell-Replete Peripheral Blood Haploidentical Donor Transplantation Is Associated with Poor Survival and Anti-IL-6 Therapy Is Safe and Well Tolerated. Biol Blood Marrow Transplant. 2016 Oct;22(10):1851-1860. doi: 10.1016/j.bbmt.2016.06.010. Epub 2016 Jun 16.

  PMID: 27318038 BACKGROUND

• Handgretinger R, Klingebiel T, Lang P, Schumm M, Neu S, Geiselhart A, Bader P, Schlegel PG, Greil J, Stachel D, Herzog RJ, Niethammer D. Megadose transplantation of purified peripheral blood CD34(+) progenitor cells from HLA-mismatched parental donors in children. Bone Marrow Transplant. 2001 Apr;27(8):777-83. doi: 10.1038/sj.bmt.1702996.

  PMID: 11477433 BACKGROUND

• Mancusi A, Ruggeri L, Velardi A. Haploidentical hematopoietic transplantation for the cure of leukemia: from its biology to clinical translation. Blood. 2016 Dec 8;128(23):2616-2623. doi: 10.1182/blood-2016-07-730564. Epub 2016 Oct 3.

  PMID: 27697774 BACKGROUND

• Ortin M, Raj R, Kinning E, Williams M, Darbyshire PJ. Partially matched related donor peripheral blood progenitor cell transplantation in paediatric patients adding fludarabine and anti-lymphocyte gamma-globulin. Bone Marrow Transplant. 2002 Sep;30(6):359-66. doi: 10.1038/sj.bmt.1703667.

  PMID: 12235520 BACKGROUND

• Dvorak CC, Long-Boyle JR, Holbrook-Brown L, Abdel-Azim H, Bertaina A, Vatsayan A, Talano JA, Bunin N, Anderson E, Flower A, Lalefar N, Higham CS, Kapoor N, Klein O, Odinakachukwu MC, Cho S, Jacobsohn DA, Collier W, Pulsipher MA. Effect of rabbit ATG PK on outcomes after TCR-alphabeta/CD19-depleted pediatric haploidentical HCT for hematologic malignancy. Blood Adv. 2024 Dec 10;8(23):6003-6014. doi: 10.1182/bloodadvances.2024012670.

  PMID: 39042892 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Christopher C Dvorak, MD

  Professor of Clinical Pediatrics

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christopher C. Dvorak, MD

CONTACT

415-476-0554; christopher.dvorak@ucsf.edu

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: Professor of Pediatrics

Study Record Dates

• First Submitted: February 27, 2020
• First Posted: April 7, 2020
• Study Start: December 19, 2019
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2035
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)