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Acute Lymphoblastic Leukemia (ALL)Phase 2NCT03849651

TCRαβ-depleted Progenitor Cell Graft With Additional Memory T-cell DLI, Plus Selected Use of Blinatumomab, in Naive T-cell Depleted Haploidentical Donor Hematopoietc Cell Transplantation for Hematologic Malignancies

A Phase 2 study testing Cyclophosphamide, Fludarabine and Thiotepa in people with Acute Lymphoblastic Leukemia (ALL) and Acute Myeloid Leukemia (AML), run by St. Jude Children's Research Hospital at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Patients less than or equal to 21 years old with high-risk hematologic malignancies who would likely benefit from allogeneic hematopoietic cell transplantation (HCT). Patients with a suitable HLA matched sibling or unrelated donor identified will be eligible for participation ONLY if the donor is not available in the… Read more about this study

Who is it for?
Ages Up to 21 years
What is being tested?
Cyclophosphamide, Fludarabine and Thiotepa
Could I receive a placebo?
No, everyone receives an active treatment
How many people
69 participants
Where
1 siteUnited States
Study dates
31 Jan 2019to 31 Dec 2027
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Age less than or equal to 21 years.
  • Does not have a suitable HLA-matched sibling donor (MSD) or volunteer 10/10 HLA-matched unrelated donor (MUD) available in the necessary time for progenitor cell donation.
  • Has a suitable single haplotype matched (≥ 3 of 6) family member donor.
  • High risk hematologic malignancy. High risk ALL in CR1. Examples include, but not limited to: t(9;22) with persistent or recurrent transcript, hypodiploid cytogenetics, MRD >1% at the end of induction, M2 or greater marrow at the end of induction, recurrent or rising MRD after induction, Infants with MLL fusion or t(4;11), relapse after prior CART therapy.
  • ALL in High risk CR2. Examples include, but not limited to t(9;22), BM relapse <36 mo CR1 or <6mo after completion of therapy, any T-ALL, very early (< 6mo CR1) isolated CNS relapse, late BM relapse with poor response to standard reinduction therapy(e.g. MRD positive or recurrence after two blocks), relapse after prior CART therapy.
  • ALL in CR3 or subsequent.
Show all 36Show fewer
  • AML in high risk CR1 (diagnosis of AML includes myeloid sarcoma). Examples include but not limited to: preceding MDS or MDS-related AML, FAB M0, FAB M6, FAB M7 with high risk genetics such as ML not t(1;22), MRD > 0.1% after two cycles of induction, MRD > 1% after one cycle of induction, FLT3-ITD in combination with NUP98-NSD1 fusion or WT1 mutation, any high risk cytogenetics such as: DEK-NUP214 [t(6;9)], KAT6A-CREBBP [t(8;16)], RUNX1-CBFA2T3 [t(16;21)], -7, -5, 5q-, KMT2A-MLLT10 [t(6;11)], KMT2A-MLLT4 [t(10;11)], inv(3)(q21q26.2), CBFA2T3-GLIS2 [inv(16)(p13.3q24.3)], NUP98-KDM5A [t(11;12)(p15;p13)], ETV6-HLXB [t(7;12)(q36;p13)], NUP98-HOXA9 [t(7;11)(p15.4;p15)], NUP98-NSD1.
  • AML in CR2 or subsequent.
  • Therapy related AML, with prior malignancy in CR > 12mo
  • MDS, primary or secondary
  • NK cell, biphenotypic, or undifferentiated leukemia in CR1 or subsequent.
  • CML in accelerated phase, or in chronic phase with persistent molecular positivity or intolerance to tyrosine kinase inhibitor.
  • Hodgkin lymphoma in CR2 or subsequent after failure of prior autologous HCT, or unable to mobilize progenitor cells for autologous HCT.
  • Non-Hodgkin lymphoma in CR2 or subsequent after failure of prior autologous HCT, or unable to mobilize progenitor cells for autologous HCT.
  • JMML
  • If prior CNS leukemia, it must be treated and in CNS CR
  • Does not have any other active malignancy other than the one for which this HCT is indicated.
  • No prior allogeneic HCT, and no autologous HCT within the previous 12 months.
  • Patient must fulfill pre-transplant organ function criteria:
  • 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.
  • Not pregnant. If female with child bearing potential, must be confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment.
  • Not breast feeding
  • Does not have current uncontrolled bacterial, fungal, or viral infection.
  • At least single haplotype matched (≥ 3 of 6) family member
  • At least 18 years of age.
  • HIV negative.
  • Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female).
  • Not breast feeding.
  • 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

  • -

Trial locations and contacts

1 site in 1 country.

United States1 site

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

Other trials in United States

About this study

Patients less than or equal to 21 years old with high-risk hematologic malignancies who would likely benefit from allogeneic hematopoietic cell transplantation (HCT). Patients with a suitable HLA matched sibling or unrelated donor identified will be eligible for participation ONLY if the donor is not available in the necessary time.

The purpose of the study is to learn more about the effects (good and bad) of transplanting blood cells donated by a family member, and that have been modified in a laboratory to remove the type of T cells known to cause graft-vs.-host disease, to children and young adults with a high risk cancer that is in remission but is at high risk of relapse. This study will give donor cells that have been TCRαβ-depleted. The TCR (T-cell receptor) is a molecule that is found only on T cells. These T-cell receptors are made up of two proteins that are linked together. About 95% of all T-cells have a TCR that is composed of an alpha protein linked to a beta protein, and these will be removed. This leaves only the T cells that have a TCR made up of a gamma protein linked to a delta protein. This donor cell infusion will be followed by an additional infusion of donor memory cells (CD45RA-depleted) after donor cell engraftment.

This study will be testing the safety and effects of the chemotherapy and the donor blood cell infusions on the transplant recipient's disease and overall survival.

Read the detailed description

In this study, participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (HCT), who lack an available suitable human leukocyte antigen (HLA) matched related/sibling donor (MSD) or matched unrelated donor (MUD), will receive a TCRαβ-depleted haploidentical donor HCT with additional memory cell DLI. One course of blinatumomab will be empirically added for patients with CD19+ malignancy.

Primary Objectives

  • Determine the maximum effective dose for prophylactic CD45RA-depleted DLI when given in the early post-engraftment period.
  • Assess the efficacy of TCRαβ-depleted progenitor cell graft with additional memory T-cell DLI, plus selected use of blinatumomab, in haploidentical donor hematopoietic cell transplantation for hematologic malignancies as measured by 1 year EFS (events = relapse, death)

Secondary Objectives

  • Assess the safety and feasibility of the addition of blinatumomab in the early post- engraftment period in patients with CD19+ malignancy
  • Estimate the incidence of neutrophil and platelet engraftment, malignant relapse,event-free survival per disease subgroups (e.g. ALL vs AML), and overall survival at one-year post-transplantation.
  • Estimate incidence and severity of acute and chronic (GVHD).
  • Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.
  • To measure and describe the pharmacokinetics of rabbit ATG in HCT recipients on this study.

Exploratory Objectives

  • Record immune reconstitution parameters, including chimerism analysis, quantitative lymphocyte subsets, T cell receptor excision circle (TREC) analysis, V-beta spectratyping, and lymphocyte phenotype and function.
  • Describe the use of additional CD45RA-depleted DLI for recipients who have severe viral infections, disease recurrence or progression, or poor immune reconstitution. Assess and record efficacy of CD45RA-depleted DLI for these conditions, and all adverse events that are related to CD45RA-depleted DLI.

Blinatumomab will be given to patients with a history of CD19+ malignancy as determined by St. Jude hematopathologist review of current and historical specimens and reports. Blinatumomab dosing will begin no sooner than 1 week after CD45RA-depleted DLI and no later than Day +90. There must be no acute GVHD or it must be quiescent. ALT must be less than 5x ULN, bili less than or equal to 1.5x ULN, and creatinine less than or equal to 1.5x ULN.

If more than one family member donor is suitable, then donor selection will be based on several factors including: degree of KIR mismatching, donor-recipient matching of CMV serology, donor-recipient red blood cell compatibility, degree of HLA matching, size of the potential donor, previous use as a donor, presence of donor-specific antibody, and overall health and availability of the potential donor.

A G-CSF mobilized peripheral blood progenitor cell product (identified as HPC,A) is the preferred progenitor cell graft source. Our desired target goal will be 5 x 10^6 CD34+ cells/kg. This number of cells will be necessary to provide an adequate graft, following the various ex vivo manipulations, for prompt reconstitution. More than one collection may be needed to achieve this goal. Donors will undergo a standard hematopoietic progenitor cell mobilization regimen consisting of 5 days of GSF given subcutaneously at 10 micrograms/kilogram. The graft will be collected by leukapheresis on day 5 (and 6 if needed) of G-CSF. The HPC product will typically be collected and infused fresh, however there may be patients or logistical situations that require the HPC product to be collected early, processed, and stored frozen.

Being tested
Cyclophosphamide, Fludarabine, Thiotepa, Melphalan, G-csf
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia, Large Granular Lymphocytic, Hodgkin Disease, Lymphoma, Non-Hodgkin, Leukemia, Myelomonocytic, Juvenile, Leukemia, Myelogenous, Chronic, BCR-ABL Positive

What participants receive

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

  • CyclophosphamideDrug

    Also called Cytoxan

    Cyclophosphamide is a nitrogen mustard derivative. It acts as an alkylating agent that causes cross-linking of DNA strands by binding with nucleic acids and other intracellular structures, thus interfering with the normal function of DNA.

    intravenously (IV) once daily (QD) on day -9

  • FludarabineBiological

    Also called Fludara

    Fludarabine phosphate is a synthetic purine nucleoside analog. It acts by inhibiting DNA polymerase, ribonucleotide reductase and DNA primase by competing with the physiologic substrate, deoxyadenosine triphosphate, resulting in inhibition of DNA synthesis.

    fludarabine phosphate IV QD on days -8 to -4

  • ThiotepaDrug

    Also called Thioplex

    Thiotepa is a cell-cycle nonspecific polyfunctional alkylating agent.

  • MelphalanDrug

    Also called Alkeran

    Melphalan, a derivative of nitrogen mustard, is a bifunctional alkylating agent. Melphalan is active against tumor cells that are actively dividing or at rest.

    melphalan IV QD on days -2 to -1

  • G-csfBiological

    Also called Neupogen, Filgrastim

    G-csf (granulocytic colony stimulating factor), is a biosynthetic hematopoietic agent that is made using recombinant DNA technology in cultures of Escherichia coli. G-CSF stimulates production, maturation and activation of neutrophils. In addition, endogenous G-CSF enhances certain functions of mature neutrophils, including phagocytosis, chemotaxis and antibody--dependent cellular cytotoxicity.

  • MesnaDrug

    Also called Mesnex

    Mesna is a synthetic sulfhydryl (thiol) compound. Mesna contains free sulfhydryl groups that interact chemically with urotoxic metabolites of oxaza-phosphorine derivatives such as cyclophosphamide and ifosfamide. Following glomerular filtration, mesna disulfide is rapidly reduced in the renal tubules back to mesna, the active form of the drug.

  • CliniMACSDevice

    Also called CliniMACS Prodigy

    Cells for infusion are prepared using the CliniMACS

  • ATG (rabbit)Biological

    Also called Thymoglobulin

    Anti-thymocyte globulin is a purified, pasteurized, gamma immune globulin, obtained by immunization of rabbits with human thymocytes.

    rabbit anti-thymocyte globulin IV daily over 6 hours on days -5 to -3,

  • BlinatumomabDrug

    Also called Blincyto

    Blinatumomab is a bispecific CD19-directed CD3 T-cell engager that mediates formation of a synapse between T cells and the CD19+ target cell, resulting in lysis of that CD19+ cell.Blinatumomab will be given to patients with a history of CD19+ malignancy as determined by St. Jude hematopathologist review of current and historical specimens and reports.

    blinatumomab IV for 28 days beginning at least 1 week post-DLI

  • TCRα/β+Biological

    IV on day 0 and may receive an additional dose on day 1

  • CD19+Biological

    IV on day 0 and may receive an additional dose on day 1

  • CD45RA-depleted DLIBiological

    infusion IV

Study groups in NCT03849651
Study groupRoleWhat they receive
Transplant participantsExperimentalParticipants receive a conditioning regimen of ATG (rabbit),Cyclophosphamide 60 mg/kg intravenous once daily, mesna, fludarabine, thiotepa, melphalan, followed by HPC,A Infusion(TCRα/β+ and CD19+ depleted),HPC, A infusion (if needed to achieve goal CD34+ cell dose.CD45RA-depleted DLI will be given at least two weeks after engraftment. Blinatumomab will be given at least one week post-DLI, and only to patients with CD19+ malignancies. G-csf 5mcg/kg subcutaneous or intravenous daily until ANC >2000 for 2 consecutive days. Cells for infusion are prepared using the CliniMACS system.
Receives: Drug: Cyclophosphamide; Biological: Fludarabine; Drug: Thiotepa; Drug: Melphalan; Biological: G-csf; Drug: Mesna; Device: CliniMACS; Biological: ATG (rabbit); Drug: Blinatumomab; Biological: TCRα/β+; Biological: CD19+; Biological: CD45RA-depleted DLI

What is being measured

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

  1. Maximum Effective Dose for Prophylactic CD45RA-depleted DLI

    The maximum effective dose (MED) of CD45RA-depleted DLI, defined as the maximum value of doses that satisfy the proportion of patients with their memory T cell count measured at week 4 post-DLI more than 300/uL is more than 50% and the toxicity of grade 3-4 aGVHD is less than 20%. Dose selection used a protocol-specified algorithm.

    Measured: 4 weeks post-DLI (up to approximately 12 weeks post-transplant)

  2. One-year Event Free Survival (EFS) After Completion of the Protocol

    Kaplan-Meier estimate of the percentage of being alive and relapse free one year after the date of transplant. (Events=relapse, death)

    Measured: One year after receiving transplant

Secondary outcomes (6)

  1. The Number of Patients Experiencing Blinatumomab Permanent Discontinuation Due to Toxicity

    If the drug is held for more than 2 weeks due to toxicity, it will be permanently discontinued

    Measured: 28 days after receiving first dose of Blinatumomab (up to approximately 7 months post-transplant)

  2. The Estimate of Cumulative Incidence of Relapse

    Kalbfleisch and Prentice estimate of the percentage of experiencing relapse one year after the date of transplant. (Events=relapse, competing events=death)

    Measured: 1 year after receiving transplant]

  3. The Estimate of Overall Survival

    Kaplan-Meier estimate of the percentage of experiencing death one year after the date of transplant. (Events=death)

    Measured: One year after receiving transplant

  4. The Cumulative Incidence of Any Severity Chronic Graft-Versus-Host Disease (GVHD)

    Kalbfleisch and Prentice estimate of the percentage of experiencing any severity chronic GVHD one year after the date of transplant. (Events=chronic GVHD, competing events=death) Groups with insufficient events for confidence interval estimation have confidence intervals written as "NA to NA."

    Measured: One year after receiving transplant

  5. The Cumulative Incidence of Any Grade Acute Graft-Versus-Host Disease (GVHD)

    Kalbfleisch and Prentice estimate of the percentage of experiencing any grade acute GVHD one year after the date of transplant. (Events=acute GVHD, competing events=death) Groups with insufficient events for confidence interval estimation have confidence intervals written as "NA to NA."

    Measured: One year after receiving transplant

  6. The Cumulative Incidence of Transplant Related Mortality

    Kalbfleisch and Prentice estimate of the percentage of experiencing TRM 100 days after the date of transplant. (Events=TRM, competing events=relapse)

    Measured: 100 days after receiving transplant

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 2019
  2. Study start31 Jan 2019
  3. Primary completion7 Aug 2024
  4. Study completion31 Dec 2027 (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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
69 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03849651
Sponsor's protocol ID
HAP2HCT
Other IDs
NCI-2019-00338
Status last verified
Sep 2026
First submitted
20 Feb 2019
Last updated
15 Sep 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cyclophosphamide, Fludarabine and Thiotepa in people with Acute Lymphoblastic Leukemia (ALL) and Acute Myeloid Leukemia (AML), run by St. Jude Children's Research Hospital 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 36 inclusion and 1 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: under way, not looking for participants, as of the sponsor's last update on 15 Sep 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 phase mean?

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?

Yes. Results are posted in the registry (first posted 4 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Effective Dose for Prophylactic CD45RA-depleted DLI (time frame: 4 weeks post-DLI (up to approximately 12 weeks post-transplant)). 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 NCT03849651.

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 Sep 2026.

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