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LeukemiaPhase 1/2NCT06839456

Phase 1/2: CD45RA Depleted Stem Cell Addback to Prevent Viral or Fungal Infections Post TCRab/CD19 Depleted HSCT

A Phase 1/2 study testing Phase 1 Dose Level 1, Phase 1 Dose Level 2 and Phase 1 Dose Level 3 in people with Leukemia and High Risk Acute Lymphoblastic Leukemia, run by Children's Hospital of Philadelphia at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The major morbidities of allogeneic hematopoietic stem cell transplant (HSCT) using donors that are not human leukocyte antigen (HLA) matched siblings are graft vs host disease (GVHD) and life- threatening infections. Read more about this study

Who is it for?
Ages 1 month to 25 years
What is being tested?
Phase 1 Dose Level 1, Phase 1 Dose Level 2 and Phase 1 Dose Level 3
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
1 siteUnited States
Study dates
21 Mar 2025to Mar 2032
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 1 month to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Disease for which allogeneic HSCT may be curative.
  • Remission status of hematologic malignancies and additional disease-specific eligibility determinations will be according to standards of practice within the CHOP Cellular Immunotherapy and Transplant Program (CTTS).
  • Patients must be 25 years of age and less
  • Evaluation for organ and infectious status as per our CTTS standard operating procedure.
  • Signed consent by parent/guardian or able to give consent if 18 years of age and older.
  • Participants of childbearing potential must have a negative pregnancy test as per institutional SOP.

Who cannot join

  • Patients who have performance score less than 60.
  • No suitable donor available for mobilized peripheral stem cells.
  • Patients with Hodgkin lymphoma or non-Burkitt, non-lymphoblastic lymphoma.
  • Planned receipt of alemtuzumab during conditioning.
  • Patients with an available 10/10 HLA matched sibling donor.
  • Patients who do not meet institutional disease, organ or infectious criteria.
Show all 17Show fewer
  • Donor selection and eligibility:
  • Unrelated donor meets National Marrow Donor Program criteria for donation.
  • Related donor (at least haploidentical) willing and able to donate mobilized peripheral stem cells.
  • HLA testing/matching
  • HLA testing to be done by molecular methods for A, B, C, DRB1, DQB1
  • Related donor: Must be ≥ 5/10 match
  • Unrelated donor: 10/10 or 9/10 match
  • KIR typing for haploidentical donor for hematologic malignancies
  • Donor specific HLA antibodies (DSA) should be assessed for all subjects receiving an HLA mismatched graft (≤ 9/10).
  • Donor must be willing to undergo granulocyte colony stimulating factor (GCSF) mobilization and peripheral blood stem cell collection
  • Donors must be willing to sign consent to participate in this study.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Megan Atkinson contact

215-590-2820

cttsbmtintake@chop.edu

Linda Zitkus, BSN,RN contact

zitkusl@chop.edu

United States1 site, 1 recruiting

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

    Megan Atkinson, 215-590-2820, atkinsonm@chop.edu

    Recruiting

Other trials in United States

About this study

Official title: Phase 1/2 Study: CD45RA Depleted Peripheral Stem Cell Addback to Prevent Viral and Fungal Infections Following Alternative Donor TCRab/CD19 Depleted Hematopoietic Stem Cell Transplant

The major morbidities of allogeneic hematopoietic stem cell transplant (HSCT) using donors that are not human leukocyte antigen (HLA) matched siblings are graft vs host disease (GVHD) and life- threatening infections. T cell receptor alpha beta (TCRαβ) T lymphocyte depletion and CD19+ B lymphocyte depletion of alternative donor hematopoietic stem cell (HSC) grafts is effective in preventing GVHD, but immune reconstitution may be delayed, increasing the risk of infections. The central hypothesis of this study is that an addback of CD45RO memory T lymphocytes, derived from a fraction of the original donor peripheral stem cell product depleted of CD45RA naïve T lymphocytes, will accelerate immune reconstitution and help decrease the risk of infections in TCRab/CD19 depleted PSCT.

Read the detailed description

The risk of severe graft versus host disease (GVHD) is increased with the use of unrelated and partially matched related donors. T cell depletion reduces the risk of severe GVHD, but immune reconstitution is delayed. Important memory T cells that may protect patients from fungal and viral infections are also removed in the T depletion process. CD45RA depletion has been studied both as a single step to reduce the risk of GVHD, and also, in conjunction with αβTCR depleted hematopoietic stem cell grafts to accelerate immune reconstitution. This single institutional trial builds on data from our protocol #18-015286, NCT03810196, "CD45RA Depleted Peripheral Stem Cell Addback for Patients at Risk for Viral or Fungal Infections Post-TCRαβ/CD19 Depleted Hematopoietic Stem Cell Transplant". This prior protocol was limited to patients with hematologic malignancies using only unrelated donors as the stem cell source.

This new study will broaden the eligible diagnoses to include non-malignant transplant indications and participants with greater than or equal to 5/10 HLA matched related donors (also known as haploidentical).

This will be a phase 1 and phase 2 study depending on the donor type. Phase 1 will include patients receiving cells from mismatched/haploidentical related donors. This will be a dose escalation study to determine the maximum tolerated cell dose of the CD45RA depleted addback. Once that dose is determined, patients with this donor type will be treated as part of phase 2.

Patients receiving their cells from unrelated donors ( 9/10 or 10/10 HLA matched) will be treated as part of phase 2 with the CD45RA depleted addback cell dose that was used on our prior study. Phase 1 and phase 2 will run concurrently.

Being tested
Phase 1 Dose Level 1, Phase 1 Dose Level 2, Phase 1 Dose Level 3, Phase 2 Maximum Tolerated Dose determined in Phase 1, Phase 2 Established Dose from prior study, NCT03810196
Keywords
alpha beta T cell depletion, CD45RA, CD45RO, GVHD prevention, Memory T cells
Medical subject headings
Leukemia, Anemia, Refractory, with Excess of Blasts, Lymphoma, Non-Hodgkin, Congenital Bone Marrow Failure Syndromes, Immunologic Deficiency Syndromes, Hemoglobinopathies, Bone Marrow Failure Disorders, Metabolism, Inborn Errors

What participants receive

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

  • Phase 1 Dose Level 1Device

    Patients in the first dose level for the CD45RA depleted addback will receive 1 X 10^6 CD45RO+ T cells/kg. Once all patients in this dose group have been evaluated for acute GVHD at day 100, then we will advance to the next dose level if indicated by safety analysis.

  • Phase 1 Dose Level 2Device

    Patients in the second dose level for the CD45RA depleted addback will receive 2 X 10^6 CD45RO+ T cells/kg. Once all patients in this dose group have been evaluated for acute GVHD at day 100, then we will advance to the next dose level if indicated by safety analysis.

  • Phase 1 Dose Level 3Device

    Patients in the third and final dose level for the CD45RA depleted addback will receive 5 X 10^6 CD45RO+ T cells/kg. All patients in this dose group will be evaluated for acute GVHD at day 100. Based on these findings, the maximum tolerated dose (MTD) will be determined.

    Once MTD for the addback cell dose has been determined in Phase 1, subjects with mismatched related donors will then enroll in Phase 2.

  • Phase 2 Maximum Tolerated Dose determined in Phase 1Device

    Patients with mismatched related donors will receive the CD45RA depleted addback at the maximum tolerated dose determined in the Phase 1 portion of the study.

  • Phase 2 Established Dose from prior study, NCT03810196Device

    Patients with unrelated donors will receive the CD45RA depleted addback at the dose 5 X 10^6 CD45RO+ T cells.

Study groups in NCT06839456
Study groupRoleWhat they receive
Phase 1:TCRab/CD19 depleted PSCT with CD45RA depleted addback using mismatched related donors (MMRD)ExperimentalStem cell source: mobilized peripheral blood stem cells (PBSC) Donor type: > or = 5/10 mismatched related donor Conditioning: disease specific standard of care (SOC) regimens
Receives: Device: Phase 1 Dose Level 1; Device: Phase 1 Dose Level 2; Device: Phase 1 Dose Level 3
Phase 2:TCRab/CD19 depleted PSCT with CD45RA depleted addback at MTD found in phase 1 using MMRDExperimentalStem cell source: mobilized PBSC Donor type: > or = 5/10 mismatched related donor Conditioning: disease specific SOC regimens
Receives: Device: Phase 2 Maximum Tolerated Dose determined in Phase 1
Phase 2:TCRab/CD19 depleted PSCT with CD45RA depleted addback using unrelated donorsExperimentalStem cell source: mobilized PBSC Donor type: 9/10 or 10/10 matched unrelated donor Conditioning: disease specific SOC regimens
Receives: Device: Phase 2 Established Dose from prior study, NCT03810196

What is being measured

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

  1. Evaluate number of patients with acute graft vs host disease (aGVHD)

    Safety evaluation assessment by cumulative incidence of acute graft vs host disease (reaction of donor immune cells against host tissues) to determine percentage of patients that develop grade 3-4 aGVHD.

    Measured: Up to 100 days post-transplantation

  2. Evaluate number of patients with chronic graft vs host disease (cGVHD)

    Safety evaluation assessment by cumulative incidence and severity of chronic GVHD (graft vs host disease that occurs more than 100 days after transplant) to determine percentage of patients that develop cGVHD.

    Measured: Up to 2 years post-transplantation

Secondary outcomes (2)

  1. Evaluate time to immune reconstitution

    Evaluate time to achievement of standard immune reconstitution benchmarks following TCRαβ/CD19 depleted HSCT with CD45RA+ depleted addback, compared to historical experience with TCRαβ/CD19 depletion alone.

    Measured: 2 years

  2. Evaluate number of patients with viral reactivation

    Evaluate number of patients with viral reactivation (CMV, adenovirus, EBV, BK) following TCRαβ/CD19 depleted HSCT with CD45RA depleted addback, compared to historical experience with TCRαβ/CD19 depletion alone.

    Measured: 2 years

Timeline

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

  1. First posted21 Feb 2025
  2. Study start21 Mar 2025
  3. Primary completionMar 2031 (estimated)
  4. Study completionMar 2032 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Use of CliniMACS based system for TCRαβ/CD19 Depleted Peripheral Stem Cells and CD45RA Depleted Peripheral Stem Cell Addback. Approximately 90% of the peripheral stem cell (PSC) product will be processed using the CliniMACS system for TCRαβ and CD19 cell depletion. In addition, approximately 10% of the PSCs will undergo CD45RA depletion also using the CliniMACS system. Processing is completed in accordance with the Investigator Brochure and Technical Manual following the laboratory standard operating procedures (SOPs) and using aseptic technique.
Masking
None (open label)
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06839456
Sponsor's protocol ID
24-022264
Status last verified
Apr 2026
First submitted
16 Feb 2025
Last updated
15 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • Zvyagin IV, Mamedov IZ, Tatarinova OV, Komech EA, Kurnikova EE, Boyakova EV, Brilliantova V, Shelikhova LN, Balashov DN, Shugay M, Sycheva AL, Kasatskaya SA, Lebedev YB, Maschan AA, Maschan MA, Chudakov DM. Tracking T-cell immune reconstitution after TCRalphabeta/CD19-depleted hematopoietic cells transplantation in children. Leukemia. 2017 May;31(5):1145-1153. doi: 10.1038/leu.2016.321. Epub 2016 Nov 4.

    PubMed 27811849

  • Anderson BE, McNiff J, Yan J, Doyle H, Mamula M, Shlomchik MJ, Shlomchik WD. Memory CD4+ T cells do not induce graft-versus-host disease. J Clin Invest. 2003 Jul;112(1):101-8. doi: 10.1172/JCI17601.

    PubMed 12840064

  • Zheng H, Matte-Martone C, Li H, Anderson BE, Venketesan S, Sheng Tan H, Jain D, McNiff J, Shlomchik WD. Effector memory CD4+ T cells mediate graft-versus-leukemia without inducing graft-versus-host disease. Blood. 2008 Feb 15;111(4):2476-84. doi: 10.1182/blood-2007-08-109678. Epub 2007 Nov 28.

    PubMed 18045967

  • Teschner D, Distler E, Wehler D, Frey M, Marandiuc D, Langeveld K, Theobald M, Thomas S, Herr W. Depletion of naive T cells using clinical grade magnetic CD45RA beads: a new approach for GVHD prophylaxis. Bone Marrow Transplant. 2014 Jan;49(1):138-44. doi: 10.1038/bmt.2013.114. Epub 2013 Aug 12.

    PubMed 23933765

  • Bleakley M, Heimfeld S, Jones LA, Turtle C, Krause D, Riddell SR, Shlomchik W. Engineering human peripheral blood stem cell grafts that are depleted of naive T cells and retain functional pathogen-specific memory T cells. Biol Blood Marrow Transplant. 2014 May;20(5):705-16. doi: 10.1016/j.bbmt.2014.01.032. Epub 2014 Feb 11.

    PubMed 24525279

  • Bleakley M, Heimfeld S, Loeb KR, Jones LA, Chaney C, Seropian S, Gooley TA, Sommermeyer F, Riddell SR, Shlomchik WD. Outcomes of acute leukemia patients transplanted with naive T cell-depleted stem cell grafts. J Clin Invest. 2015 Jul 1;125(7):2677-89. doi: 10.1172/JCI81229. Epub 2015 Jun 8.

    PubMed 26053664

  • Touzot F, Neven B, Dal-Cortivo L, Gabrion A, Moshous D, Cros G, Chomton M, Luby JM, Terniaux B, Magalon J, Picard C, Blanche S, Fischer A, Cavazzana M. CD45RA depletion in HLA-mismatched allogeneic hematopoietic stem cell transplantation for primary combined immunodeficiency: A preliminary study. J Allergy Clin Immunol. 2015 May;135(5):1303-9.e1-3. doi: 10.1016/j.jaci.2014.08.019. Epub 2014 Oct 3.

    PubMed 25282016

  • Triplett BM, Shook DR, Eldridge P, Li Y, Kang G, Dallas M, Hartford C, Srinivasan A, Chan WK, Suwannasaen D, Inaba H, Merchant TE, Pui CH, Leung W. Rapid memory T-cell reconstitution recapitulating CD45RA-depleted haploidentical transplant graft content in patients with hematologic malignancies. Bone Marrow Transplant. 2015 Jul;50(7):968-77. doi: 10.1038/bmt.2014.324. Epub 2015 Feb 9.

    PubMed 25665048

  • Shook DR, Triplett BM, Eldridge PW, Kang G, Srinivasan A, Leung W. Haploidentical stem cell transplantation augmented by CD45RA negative lymphocytes provides rapid engraftment and excellent tolerability. Pediatr Blood Cancer. 2015 Apr;62(4):666-73. doi: 10.1002/pbc.25352. Epub 2015 Jan 5.

    PubMed 25559618

  • Brodszki N, Turkiewicz D, Toporski J, Truedsson L, Dykes J. Novel treatment of severe combined immunodeficiency utilizing ex-vivo T-cell depleted haploidentical hematopoietic stem cell transplantation and CD45RA+ depleted donor lymphocyte infusions. Orphanet J Rare Dis. 2016 Jan 15;11:5. doi: 10.1186/s13023-016-0385-3.

    PubMed 26768987

  • Al-Akioui Sanz K, Echecopar Parente C, Ferreras C, Menendez Ribes M, Navarro A, Mestre C, Clares L, Vicario JL, Balas A, De Paz R, Lopez Granados E, Sanchez Zapardiel E, Jimenez C, Lopez-Oliva M, Ramos E, Hernandez-Oliveros F, Perez-Martinez A. Familial CD45RA- T cells to treat severe refractory infections in immunocompromised patients. Front Med (Lausanne). 2023 Feb 8;10:1083215. doi: 10.3389/fmed.2023.1083215. eCollection 2023.

    PubMed 36844219

  • Leahy AB, Li Y, Talano JA, Elgarten CW, Seif AE, Wang Y, Johnson B, Monos DS, Kadauke S, Olson TS, Freedman J, Wray L, Grupp SA, Bunin N. Unrelated donor alpha/beta T cell- and B cell-depleted HSCT for the treatment of pediatric acute leukemia. Blood Adv. 2022 Feb 22;6(4):1175-1185. doi: 10.1182/bloodadvances.2021005492.

    PubMed 34872106

  • Mamcarz E, Madden R, Qudeimat A, Srinivasan A, Talleur A, Sharma A, Suliman A, Maron G, Sunkara A, Kang G, Leung W, Gottschalk S, Triplett BM. Improved survival rate in T-cell depleted haploidentical hematopoietic cell transplantation over the last 15 years at a single institution. Bone Marrow Transplant. 2020 May;55(5):929-938. doi: 10.1038/s41409-019-0750-7. Epub 2019 Nov 18.

    PubMed 31740766

  • Maung KK, Chen BJ, Barak I, Li Z, Rizzieri DA, Gasparetto C, Sullivan KM, Long GD, Engemann AM, Waters-Pick B, Nichols KR, Lopez R, Kang Y, Sarantopoulos S, Sung AD, Chao NJ, Horwitz ME. Phase I dose escalation study of naive T-cell depleted donor lymphocyte infusion following allogeneic stem cell transplantation. Bone Marrow Transplant. 2021 Jan;56(1):137-143. doi: 10.1038/s41409-020-0991-5. Epub 2020 Jul 5.

    PubMed 32624583

  • Naik S, Triplett BM. Selective depletion of naive T cells by targeting CD45RA. Front Oncol. 2023 Jan 27;12:1009143. doi: 10.3389/fonc.2022.1009143. eCollection 2022. No abstract available.

    PubMed 36776371

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Phase 1 Dose Level 1, Phase 1 Dose Level 2 and Phase 1 Dose Level 3 in people with Leukemia and High Risk Acute Lymphoblastic Leukemia, run by Children's Hospital of Philadelphia at 1 site in United States.

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 6 inclusion and 17 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: looking for participants now, as of the sponsor's last update on 15 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

Contact Megan Atkinson (215-590-2820, cttsbmtintake@chop.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluate number of patients with acute graft vs host disease (aGVHD) (time frame: Up to 100 days post-transplantation). The study lists 2 primary outcomes in all. 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 NCT06839456, which also lists 16 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 15 Apr 2026.

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