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Allogeneic Hematopoietic Cell Transplantation (HCT)Phase 1NCT05088356

Reduced Intensity Allogeneic HCT in Advanced Hematologic Malignancies w/T-Cell Depleted Graft

A Phase 1 study testing Purified regulatory T-cells (Treg) plus CD34+ HSPC, Fludarabine and Melphalan in people with Allogeneic Hematopoietic Cell Transplantation (HCT) and Advanced Hematologic Malignancies, run by Stanford University 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

Reduced intensity conditioning (RIC) has emerged and been increasingly adopted as a modality to allow preparative conditioning pre transplant to be tolerated by older adults or those patients that are otherwise unfit for myeloablative conditioning. Read more about this study

Who is it for?
Ages 18 to 75 yearsHealthy volunteers can take part
What is being tested?
Purified regulatory T-cells (Treg) plus CD34+ HSPC, Fludarabine and Melphalan
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
1 siteUnited States
Study dates
7 Sep 2021to May 2028
Phase
Phase 1
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 18 to 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Recipient Inclusion Criteria a. Patients with the following diseases that are histopathologically-confirmed are eligible
  • Acute myeloid, lymphoid, or mixed phenotype leukemia in complete remission (CR) or CR with incomplete hematologic recovery (CRi) or beyond first complete remission (CR1) without the presence of minimal residual disease
  • Acute myeloid, leukemia, or mixed phenotype leukemia that is either:
  • Not in morphologic CR with bone marrow infiltration by leukemic blasts of ≤10%, or
  • In morphologic CR with evidence of minimal residual disease positivity by either multiparametric flow cytometric analysis or by a nucleic acid-based technique
  • Primary refractory acute myeloid, lymphoid, or mixed phenotype leukemia
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  • Chronic myelogenous leukemia (accelerated, blast or second chronic phase)
  • Myelodysplastic syndromes
  • Myeloproliferative syndromes b. Match to the patient as follows:
  • For Arm A1 (CLOSED):
  • Availability of a 8/8 or 7/8 HLA-matched donor (related or unrelated) defined by Class I (HLA-A, -B, -C) serologic typing (or higher resolution) and Class II (HLA-DRB1) molecular typing.
  • If the donor is a 7/8 HLA-match, the mismatch must be a permissive allelic mismatch as assessed by an independent HLA and transplantation expert.
  • For Arm A1 and Arm A3:
  • Availability of a 8/8 HLA-matched donor (related or unrelated) defined by Class I (HLA-A, -B, -C) serologic typing (or higher resolution) and Class II (HLA-DRB1) molecular typing.
  • For Arm B (CLOSED):
  • Availability of a haploidentical donor who is a ≥ 4/8 but <7/8 match at HLA-A, -B, -C, and -DRB1 (typed using DNA-based high-resolution methods), with at most one mismatch per locus
  • For Arm C1 (CLOSED) and C2:
  • Availability of a 8/8 HLA matched donor (related or unrelated) defined by Class I (HLA-A, B, C) serologic typing (or higher resolution) and Class II (HLA DRB1) molecular typing.
  • Age ≥ 18 and ≤75 years old at the time of enrollment. For Arm A4, age >/= 18 and </= 78 years of age.
  • Left ventricular ejection fraction (LVEF) ≥ 45% e. Diffusing capacity of the lungs for carbon monoxide (DLCO) ≥ 50% f. Calculated creatinine clearance ≥ 50 mL/min or creatinine < 2.0 mg/dL g. SGPT and SGOT ≤ 3 x ULN, unless elevated secondary to disease Total bilirubin ≤ 2 x ULN (patients with Gilbert's syndrome may be included at the discretion of the PI or where hemolysis has been excluded h. Negative serum or urine beta-HCG test in females of childbearing potential within 3 weeks of registration i. Karnofsky performance status ≥ 70%
  • Donor Inclusion Criteria
  • Age ≥ 18 and ≤ 75 years of age
  • Karnofsky performance status of ≥ 70% defined by institutional standards
  • Seronegative for HIV-1 RNA PCR; HIV 1 and HIV 2 ab (antibody); HTLV-1 and HTLV-2 ab; PCR+ or sAg (surface antigen) hepatitis B ; or PCR or sAg negative for hepatitis C; negative for the Treponema palladum antibody Syphillis screen; and negative for HIV-1 and hepatitis C by nucleic acid testing (NAT) within 30 days of apheresis collection.
  • In the case that T palladum antibody tests are positive, donors must:
  • Be evaluated and show no evidence of syphilis infection of any stage by physical exam and history, or Have completed effective antibiotic therapy to treat syphilis, or Have a documented negative non-treponemal test (such as RPR) or in the case of a positive non-treponemal test must be evaluated by an infectious disease expert to evaluate for alternative causes of test positivity and confirm no evidence of active syphilitic disease e. Match to the patient as follows: a. Arm A1(CLOSED):
  • Must be a related or unrelated, 8/8 or 7/8-HLA match to recipient at HLAA, -B, -C, and -DRB1. If 7/8 HLA-matched, must be with permissive allelic HLA mismatch as assessed by an independent HLA and transplantation expert.
  • Arm A2 (CLOSED) and Arm A3 (CLOSED):
  • Must be a related or unrelated, 8/8 HLA match to recipient at HLA A, B, C, and DRB1
  • Arm B (CLOSED):
  • Must be a haploidentical donor who is ≥ 4/8 but < 7/8 match at HLA-A, -B,
  • -C, and -DRB1, with at most one mismatch per locus.
  • Arm C1 (CLOSED) and Arm C2:
  • Must be a related or unrelated 7/8 HLA matched to recipient at HLA A, B, C, DRB1 or -DQB1
  • Must be willing to donate PBSC for up two consecutive days g. Female donors of child-bearing potential must have a negative serum or urine beta HCG test within 3 weeks of mobilization h. Capable of undergoing leukapheresis, have adequate venous access, and be willing to undergo insertion of a central catheter should leukapheresis via peripheral vein be inadequate i. Agreeable to 2nd donation of PBPC (or bone marrow harvest) in the event of graft failure j. The donor or legal guardian greater than 18 years of age, capable of signing an IRB approved consent form. k. Meets other criteria for donation as specified by standard NMDP guidelines (NMDP donors) or institutional standards (non-NMDP donors) l. Donors not meeting federal eligibility criterion, may nonetheless be included if either apply as follows per 21 CFR § 1271.65:
  • The donor is a first-degree or second-degree blood relative of the recipient, or
  • Documented urgent medical need (DUMN), meaning no comparable human cell product is available and the recipient is likely to suffer death or serious morbidity without the human cell product, as attested by the Investigator or sub-investigator

Who cannot join

  • Recipient Exclusion Criteria
  • Seropositive for any of the following:
  • HIV antibodies; hepatitis B surface antigen (sAg); hepatitis C antibodies
  • Patients deemed candidates for fully myeloablative preparative conditioning regimens
  • Candidate for autologous transplant e. Hepatitis B or C with SGPT or SGOT > 3 x ULN f. HIV-positive g. Active uncontrolled bacterial, viral or fungal infection, defined as currently taking antimicrobial therapy and progression of clinical symptoms. h. Uncontrolled CNS disease involvement i. Pregnant or a lactating female j. Positive serum or urine beta-HCG test in females of childbearing potential within 3 weeks of registration k. Psychosocial circumstances that preclude the patient being able to go through transplant or participate responsibly in follow-up care l. Known allergy or hypersensitivity to, or intolerance of, tacrolimus m. Positive anti-donor HLA antibodies against a mismatched allele in the selected donor determined by either:
  • A positive crossmatch of any titer; or
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  • The presence of anti-donor HLA antibody to any HLA locus n. Any uncontrolled autoimmune disease requiring active immunosuppressive treatment o. Concurrent malignancies or active disease within 1 year, except nonmelanomatous skin cancers that have been curatively resected
  • Donor Exclusion Criteria
  • Evidence of active infection
  • Seropositive for HIV-1 or-2, HTLV-1 or -2
  • Medical, physical, or psychological reason that would place the donor at increased risk for complications from growth factor or leukapheresis
  • Lactating female

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Stanford University

    Stanford, California, 94304

Other trials in United States

About this study

Official title: Phase 1 Trial for Patients With Advanced Hematologic Malignancies Undergoing Reduced Intensity Allogeneic HCT With a T-cell Depleted Graft With Infusion of Conventional T-cells and Regulatory T-cells

Reduced intensity conditioning (RIC) has emerged and been increasingly adopted as a modality to allow preparative conditioning pre transplant to be tolerated by older adults or those patients that are otherwise unfit for myeloablative conditioning. In this study, we aim to use RIC followed by matched related/unrelated donor, 7/8 matched related/unrelated donor, or haploidentical donor peripheral blood stem cell transplantation. Standard strategies to control the alloreactivity following HCT utilize immunosuppressive or cytotoxic medications. In this study, we explore donor graft engineering to enrich for immmunoregulatory populations to facilitate post transplantation immune reconstitution while minimizing graft versus host disease (GVHD) with post-transplant immunosuppressive agents.

Read the detailed description

The objectives for the study are listed below:

Primary Objectives

*Determine the safety, and feasibility of administration of several dose combinations of conventional T-cells (Tcon) and regulatory T-cells (Treg) in subjects undergoing allogeneic hematopoietic cell transplantation (HCT) with related/unrelated HLA-matched or mismatched donors, or haploidentical donors with reduced intensity conditioning preparative regimen.

Secondary Objectives

  • To determine the GVHD-free relapse-free survival (GRFS) post-HCT
  • To determine the overall survival (OS) post-HCT
  • To measure the incidence and severity of acute and chronic GVHD

Exploratory Objectives

  • To measure the incidence of serious infections
  • To measure the incidence and timing of engraftment
  • To measure T cell immunity reconstitution parameters
Being tested
Purified regulatory T-cells (Treg) plus CD34+ HSPC, Fludarabine, Melphalan, CliniMACS CD34 Reagent System, Tacrolimus
Keywords
Reduced intensity conditioning (RIC), GVHD
Medical subject headings
Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Myelodysplastic Syndromes, Myeloproliferative Disorders

What participants receive

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

  • Purified regulatory T-cells (Treg) plus CD34+ HSPCDrug

    Purified regulatory T-cells (Treg) plus CD34+ hematopoietic progenitor cells ("CD34+ HSPC"), followed by conventional T-cells (Tcon) Manufactured at SCTT Laboratory, dose 1x10^6 cells/ kg to 3x10^6 cells/kg

  • FludarabineDrug

    Also called Beneflur, SH T 586, fludarabine monophosphate

    Fludarabine (160 mg/m2)

  • MelphalanDrug

    Also called Melphalanum

    Melphalan (50 mg/m2)

  • CliniMACS CD34 Reagent SystemDevice

    The CliniMACS® CD34 Reagent System is a medical device that is used in vitro to select and enrich specific cell populations is manufactured by Miltenyi Biotec

  • TacrolimusDrug

    Also called Prograf, Advagraf, fujimycin

    4-6ng/mL

  • CyclophosphamideDrug

    Also called alkylating agent

    40mg/kg

  • PlerixaforDrug

    Also called Mozobil, AMD 3100, LM-3100

    Dose 0.24 mg/kg, manufactured by Genzyme

  • Filgrastim granulocyte colony-stimulating factor (G-CSF) or equivalentDrug

    Also called filgrastim XM02

    Single-use vials contain either 300 mcg or 480 mcg filgrastim at a fill volume of 1.0 mL or 1.6 mL

  • ThiotepaDrug

    Also called Tepandina

    Thiotepa 10 mg/kg

  • Mycophenolate Mofetil (MMF)Drug

    Also called CellCept

    MMF 1000 mg BID

  • RuxolitinibDrug

    Also called Jakafi

    Ruxolitinib 5 mg BID

  • SirolimusDrug

    Also called Rapamune, rapamycin

    5 - 8 ng/mL

Study groups in NCT05088356
Study groupRoleWhat they receive
Arm A1: Matched related/matched unrelated donor transplantation (closed)ExperimentalSubjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant:. * Fludarabine (160 mg/m2) * Melphalan (50 mg/m2) * TBI (4Gy) All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
Receives: Drug: Purified regulatory T-cells (Treg) plus CD34+ HSPC; Drug: Fludarabine; Drug: Melphalan; Drug: Tacrolimus; Drug: Plerixafor; Drug: Filgrastim granulocyte colony-stimulating factor (G-CSF) or equivalent
Arm B: Haploidentical transplantation (closed)ExperimentalSubjects without an identified matched related or matched unrelated donor will receive a haploidentical transplantation with reduced intensity preparative conditioning: -. Fludarabine (160 mg/m2) * Melphalan (100 mg/m2 * TBI (4Gy) Patients will receive GVHD prophylaxis with post-transplant cyclophosphamide and tacrolimus.
Receives: Drug: Purified regulatory T-cells (Treg) plus CD34+ HSPC; Drug: Fludarabine; Drug: Melphalan; Device: CliniMACS CD34 Reagent System; Drug: Tacrolimus; Drug: Cyclophosphamide; Drug: Plerixafor; Drug: Filgrastim granulocyte colony-stimulating factor (G-CSF) or equivalent
Arm A2: Fully matched (8/8) related/unrelated donor transplantation (closed)ExperimentalSubjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (10 mg/kg) * TBI (4Gy) All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
Receives: Drug: Purified regulatory T-cells (Treg) plus CD34+ HSPC; Drug: Fludarabine; Drug: Tacrolimus; Drug: Plerixafor; Drug: Filgrastim granulocyte colony-stimulating factor (G-CSF) or equivalent; Drug: Thiotepa
Arm A3: Fully (8/8) matched related/unrelated donor transplantation (closed)ExperimentalSubjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (5 mg/kg) * TBI (2-3 Gy). All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
Receives: Drug: Purified regulatory T-cells (Treg) plus CD34+ HSPC; Drug: Fludarabine; Drug: Tacrolimus; Drug: Plerixafor; Drug: Filgrastim granulocyte colony-stimulating factor (G-CSF) or equivalent; Drug: Thiotepa
Arm C1:7/8 mismatched related/unrelated donor transplantation (closed)ExperimentalSubjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (10 mg/kg) * TBI (4 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and mycophenolate mofetil (MMF).
Receives: Drug: Purified regulatory T-cells (Treg) plus CD34+ HSPC; Drug: Fludarabine; Drug: Tacrolimus; Drug: Plerixafor; Drug: Filgrastim granulocyte colony-stimulating factor (G-CSF) or equivalent; Drug: Thiotepa; Drug: Mycophenolate Mofetil (MMF)
Arm C2: 7/8 mismatched related/unrelated donor transplantationExperimentalSubjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (5 mg/kg) * TBI (2-3 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and ruxolitinib.
Receives: Drug: Purified regulatory T-cells (Treg) plus CD34+ HSPC; Drug: Fludarabine; Drug: Tacrolimus; Drug: Plerixafor; Drug: Filgrastim granulocyte colony-stimulating factor (G-CSF) or equivalent; Drug: Thiotepa; Drug: Ruxolitinib; Drug: Sirolimus
Arm A4: 8/8 mismatched related/unrelated donor transplantationExperimentalSubjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (7.5 mg/kg) * TBI (2-3 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus
Receives: Drug: Purified regulatory T-cells (Treg) plus CD34+ HSPC; Drug: Fludarabine; Drug: Tacrolimus; Drug: Plerixafor; Drug: Filgrastim granulocyte colony-stimulating factor (G-CSF) or equivalent; Drug: Thiotepa

What is being measured

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

  1. Determine the GVHD-free relapse-free survival (GRFS) post-HCT ( Arm-A)

    Clinical effect will be assessed as graft vs host disease (GVHD)-free relapse free survival (GRFS), GVHD-free is defined as no GVHD symptoms, and relapse free survival is defined as survival at 12 months without relapse. The outcome will be measured in Arm A only.

    Measured: 12 months

  2. Determine the overall survival (OS) post-HCT ( Arm-B)

    Overall survival is measured as number of participants alive. Alive at the time of last observation will be censored.

    Measured: 2 years

  3. Incidence of Grade III-IV acute GVHD

    Acute GVHD will be staged and graded per Mount Sinai Acute GvHD International Consortium (MAGIC) Standardization criteria.

    Measured: At baseline, day +30, 60, 90, 180, year 1 and year 2

  4. The incidence and timing of primary graft failure

    Primary graft failure is defined as being alive with donor CD3 chimerism <5% at day +30 after transplant without recovery of neutrophils (i.e. without achieving an absolute neutrophil count [ANC] ≥ 500/mm3 for 3 consecutive days) at Day+28

    Measured: 2 years from the Day 0 (day of CD34+ peripheral blood stem cell infusion

  5. Donor CD3 chimerism at Day+60 post-HCT

    Defined as a percentage on donor CD3 cells chimerism at day +60 after transplantation.

    Measured: 2 years from the Day 0 (day of CD34+ peripheral blood stem cell infusion)

Secondary outcomes (9)

  1. GVHD-relapse-free survival

    Clinical effect will be assessed as graft vs host disease (GVHD)-free relapse free survival (GRFS), GVHD-free is defined as no GVHD grade 3 and 4, and relapse free survival is defined as survival at 12 months without relapse.

    Measured: 12 months

  2. Overall survival

    Overall survival is measured as number of participants alive. Alive at the time of last observation will be censored.

    Measured: 12 months

  3. Secondary graft failure

    Secondary graft failure (defined by donor CD3 chimerism <5% at day +30 after transplant) and neutrophil engraftment followed by subsequent decline in ANC < 500/mm3 unresponsive to growth factor therapy, by Day +100

    Measured: from Day 0 through 100 days

  4. Treatment-emergent adverse events (TEAs)

    TEAEs will be categorized by the System Organ Class and preferred term and will be graded according to the CTCAE version 5.0

    Measured: from Day 0 through 100 days

  5. Acute GVHD (all grades)

    Acute GVHD (all grades) will be reported

    Measured: from Day 0 through 100 days

  6. Steroid-refractory acute GVHD

    Steroid refractory acute GVHD will be defined as per the EBMT-NIH-CIBMTR Task Force position statement

    Measured: within 3-5 days of therapy onset

  7. Non-relapse mortality (NRM)

    Non-relapse mortality is measured as number of participants died without relapse/ recurrent disease. Subjects without evidence of relapse/progression at last follow-up date or date of death will be censored.

    Measured: 12 months

  8. Disease-free survival (DFS)

    Overall survival is measured as number of participants alive and in remission. Alive in remission at the time of last observation will be censored.

    Measured: 12 months

  9. Chronic GVHD (limited or extensive)

    Chronic GVHD will be diagnosed per 2014 International NIH Chronic GVHD Diagnosis and Staging Consensus Working Group criteria (Jagasia 2015). Chronic GVHD scored according to the first day of chronic GVHD onset will be used to calculate cumulative incidence curves. Subjects will be followed for 2 years from the Day 0 (day of CD34+ peripheral blood stem cell infusion) for estimation of cGVHD incidence.

    Measured: from Day 0 through Year 2

Timeline

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

  1. First posted21 Oct 2021
  2. Study start7 Sep 2021
  3. Primary completionMay 2028 (estimated)
  4. Study completionMay 2028 (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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05088356
Sponsor's protocol ID
IRB-60439
Other IDs
NCI-2021-12228
Status last verified
May 2026
First submitted
11 Oct 2021
Last updated
12 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Purified regulatory T-cells (Treg) plus CD34+ HSPC, Fludarabine and Melphalan in people with Allogeneic Hematopoietic Cell Transplantation (HCT) and Advanced Hematologic Malignancies, run by Stanford University 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 37 inclusion and 12 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 12 May 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 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.

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?

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?

Determine the GVHD-free relapse-free survival (GRFS) post-HCT ( Arm-A) (time frame: 12 months). The study lists 5 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 NCT05088356.

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 12 May 2026.

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