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

ConditionsLeukemiaHigh Risk Acute Lymphoblastic LeukemiaHigh Risk Acute Myeloid LeukemiaRelapse LeukemiaMDS (Myelodysplastic Syndrome)Relapsed Non-Hodgkin LymphomaAcquired Aplastic AnemiaInherited BMF SyndromeImmunodeficiencyPrimary Immune Regulatory DisorderHemoglobinopathiesBone Marrow FailureInborn Errors of MetabolismHLH
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age1-25
SponsorChildren's Hospital of Philadelphia

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Phase 1 Dose Level 1

    Device

    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 2

    Device

    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 3

    Device

    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 1

    Device

    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, NCT03810196

    Device

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

Treatment groups

100 Participants
are divided into 3 treatment groups
Group A: Phase 1:TCRab/CD19 depleted PSCT with CD45RA depleted addback using mismatched related donors (MMRD)Experimental treatment 3 interventions
Group B: Phase 2:TCRab/CD19 depleted PSCT with CD45RA depleted addback at MTD found in phase 1 using MMRDExperimental treatment 1 intervention
Group C: Phase 2:TCRab/CD19 depleted PSCT with CD45RA depleted addback using unrelated donorsExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

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.

Time frame
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.

Time frame
Up to 2 years post-transplantation

Secondary outcomes

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.

Time frame
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.

Time frame
2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Children's Hospital of Philadelphia

Lead sponsor

Source ClinicalTrials.gov
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