Hematologic MalignancyPhase 1NCT07052370
TCRαβ-depleted Progenitor Cell Graft With Early Memory T-cell DLI, Plus Selected Use of Blinatumomab, in naïve T-cell Depleted Haploidentical Donor Hematopoietic Cell Transplantation for Hematologic Malignancies
A Phase 1 study testing Thymoglobulin, Cyclophosphamide and Fludarabine in people with Hematologic Malignancy, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial summary
This is a phase I, prospective clinical trial studying the safety and feasibility of providing early memory T-cell DLI. The primary objective is: To assess the safety and feasibility of early CD45RA-depleted DLI administration. Read more about this study
- Who is it for?
- Ages Up to 21 yearsHealthy volunteers can take part
- Conditions the study is for
- Hematologic Malignancy
- What is being tested?
- Thymoglobulin, Cyclophosphamide and Fludarabine
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Sep 2025to Dec 2030
- Phase
- Phase 1
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
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Recipient:
- Age less than or equal to 21 years
- High risk hematologic malignancy whereas allogeneic transplantation is the current standard of care. This includes (but is not limited to):
- High risk ALL in CR1 or CR2,
- any ALL in CR3 or subsequent;
- AML in high risk CR1 (AML diagnosis includes myeloid sarcoma),
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- any AML in CR2 or subsequent,
- any therapy related AML;
- MDS (primary or secondary),
- NK cell, biphenotypic, or undifferentiated leukemia/lymphoma in CR1 or subsequent;
- CML in accelerated phase, or in chronic phase with persistent molecular positivity or intolerance to tyrosine kinase inhibitor, or a history of blast crisis.
- If prior CNS leukemia, it must be treated and in CNS CR
- Left ventricular ejection fraction > 40%, or shortening fraction ≥ 25%
- Creatinine clearance (CrCl) or glomerular filtration rate (GFR) ≥ 50 ml/min/1.73m2
- Forced vital capacity (FVC) ≥ 50% of predicted value; or pulse oximetry ≥ 92% on room air if patient is unable to perform pulmonary function testing
- Karnofsky or Lansky (age dependent) performance score ≥ 50 (See APPENDIX A)
- Bilirubin ≤ 3 times the upper limit of normal for age
- Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≤ 5 times the upper limit of normal for age
- Donor:
- At least single haplotype matched (≥ 4 of 8) family member
- At least 18 years of age
- HIV negative
- Regarding donation eligibility, is identified as either:
- Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance; OR
- Does not meet 21 CFR 1271 eligibility requirements, but has a declaration of urgent medical need completed by the principal investigator or physician sub-investigator per 21 CFR 1271
Who cannot join
- Recipient:
- Has a suitable HLA-identical sibling or suitable 12/12 (HLA-A, B, C, DRB1, DQB1, and DPB1) HLA-matched unrelated donor available in an appropriate time frame.
- Any other active malignancy other than the one for which this HCT is indicated
- Received a prior allogeneic HCT at any time
- Received an autologous HCT within the previous 6 months
- Pregnant, if female is of childbearing potential, negative test must be confirmed by serum or urine pregnancy test within 14 days prior to enrollment
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- Breast feeding
- Any current uncontrolled bacterial, fungal or viral infection
- Donor:
- Pregnant, negative test must be confirmed by serum or urine pregnancy test within 14 days prior to enrollment if female
- If female, breast feeding
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Brandon Triplett, MD, 866-278-5833, referralinfo@stjude.org
About this study
This is a phase I, prospective clinical trial studying the safety and feasibility of providing early memory T-cell DLI.
The primary objective is:
- To assess the safety and feasibility of early CD45RA-depleted DLI administration.
The secondary objectives are
- To assess the safety and feasibility of the addition of blinatumomab in the early post-transplant period in patients with CD19+ malignancy.
- To measure and describe the pharmacokinetics of rabbit ATG in HCT recipients on this study.
Read the detailed description
The purpose of the study is to learn more about the effects (good and bad) of transplanting progenitor (blood making) cells and donor lymphocytes (white blood cells) donated by a partially matched family member that have been modified in a laboratory, to children and young adults with a high risk cancer that is in remission but is at high risk of relapse. This study builds upon what we have learned from recently completed studies and will be testing the safety and effects of the chemotherapy and the combination of two different types of blood cell infusions on the transplant recipient's disease and overall survival.
In this study, participants with high-risk hematologic malignancies who lack an available suitable human leukocyte antigen (HLA) matched related/sibling donor (MSD) or matched unrelated donor (MUD), will undergo allogeneic hematopoietic cell transplantation (HCT) consisting of a TCRαβ-depleted haploidentical donor product with additional memory cell donor lymphocyte infusion (DLI) given in the early postHCT time period.
Prior to the infusion of donor cells, a preparative regimen consisting of antibodies and chemotherapy will be given. The preparative regimen includes the following total dosages: ATG 5mg/kg (over days -12 to -10); Cyclophosphamide 60 mg/kg (day -9); Fludarabine 150 mg/m2 (over days -8 to -4); Thiotepa 10 mg/kg (divided in two doses on day -3); Melphalan 70 mg/m2 (over days -2 to -1). Following this regimen the TCRαβ-depleted haploidentical donor product will be given on day 0 (subsequent infusion given on day +1 if needed to achieve goal CD34+ cell dose. Approximately 2 weeks later the memory cell donor lymphocyte infusion (DLI) will be given at a dose previously determined to be safe and effective.
Blinatumomab will be empirically added for patients with CD19+ malignancy and given at least four weeks after the memory cell DLI.
- Conditions
- Hematologic Malignancy
- Being tested
- Thymoglobulin, Cyclophosphamide, Fludarabine, Thiotepa, Melphalan
- Keywords
- Hematopoietic Cell Transplant
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThymoglobulinDrug
IV
CyclophosphamideDrug
IV
FludarabineDrug
IV
ThiotepaDrug
IV
MelphalanDrug
IV
MesnaDrug
IV
FilgrastimDrug
IV
BlinatumomabDrug
IV
CliniMACSDevice
The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest.
| Study group | Role | What they receive |
|---|---|---|
| HAP3HCT Treatment | Experimental | Prior to the infusion of donor cells, a preparative regimen consisting of antibodies and chemotherapy will be given. The preparative regimen includes the following total dosages: ATG 5mg/kg (over days -12 to -10); Cyclophosphamide 60 mg/kg (day -9); Fludarabine 150 mg/m2 (over days -8 to -4); Thiotepa 10 mg/kg (divided in two doses on day -3); Melphalan 70 mg/m2 (over days -2 to -1). Following this regimen the TCRαβ-depleted haploidentical donor product will be given on day 0 (subsequent infusion given on day +1 if needed to achieve goal CD34+ cell dose. Approximately 2 weeks later the memory cell donor lymphocyte infusion (DLI) will be given at a dose previously determined to be safe and effective.
Blinatumomab will be empirically added for patients with CD19+ malignancy and given at least four weeks after the memory cell DLI. Receives: Drug: Thymoglobulin; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Thiotepa; Drug: Melphalan; Drug: Mesna; Drug: Filgrastim; Drug: Blinatumomab; Device: CliniMACS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants experiencing grade 3-4 GVHD and/or transplant related mortality (TRM).
Safety will be measured by monitoring for the incidence of grade 3-4 GVHD as well as any transplant related mortality experience. Feasibility monitoring will include 1) failure to receive protocol directed DLI among the evaluable participants; and 2) the number of days from transplant infusion to DLI infusion among evaluable participants.
Measured: Within 100 days post-transplant infusion
Secondary outcomes (2)
Number of participants experiencing safety issues or feasibility concerns related to blinatumomab administration.
Safety and feasibility will be measured by monitoring for any early discontinuation of blinatumomab.
Measured: Within 180 days post-transplant infusion
Describing pharmacokinetics of rabbit ATG in participants.
Measuring concentration of rabbit ATG levels in participants at the specified time points within the protocol.
Measured: Within 14 days post-transplant infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2025
- Study start25 Sep 2025
- Primary completionDec 2028 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematologic MalignancyStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Brandon Triplett, MD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07052370
- Sponsor's protocol ID
- HAP3HCT
- Other IDs
- NCI-2025-04293
- Status last verified
- Jun 2026
- First submitted
- 26 Jun 2025
- Last updated
- 2 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.