Phase 1-2 MAHCT w/ TCell Depleted Graft w/ Simultaneous Infusion Conventional and Regulatory T Cell
Phase 1-2 Trial for Patients With Advanced Hematologic Malignancies Undergoing Myeloablative Allogeneic HCT With a T-cell Depleted Graft With Infusion of Conventional T-cells and Regulatory T-cells
5 other identifiers
interventional
68
1 country
1
Brief Summary
This study looks at giving specific types of immune cells, called regulatory T cells and conventional T cells, to patients with blood cancers who are receiving a stem cell transplant. These cells are added back to help the immune system recover and reduce complications after the transplant.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Feb 2012
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 9, 2012
CompletedFirst Submitted
Initial submission to the registry
August 6, 2012
CompletedFirst Posted
Study publicly available on registry
August 8, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 20, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
December 20, 2023
CompletedResults Posted
Study results publicly available
August 19, 2025
CompletedAugust 19, 2025
August 1, 2025
11.9 years
August 6, 2012
February 3, 2025
August 18, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
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.
12 months
Secondary Outcomes (5)
Number of Participants With Dose-Limiting Toxicity (DLT) Within 28 Days
28 days
Number of Participants With Overall Survival (OS) at 1 Year
1 year
Number of Participants With Severity of Chronic Graft-vs-Host Disease (cGvHD) at 24 Months
2 years
Number of Participants With Incidence of Serious Infections
24 months
Number of Participants Receiving Concomitant Single-Agent Immunosuppression
2 years
Study Arms (9)
Cohort 1, Phase I: Low Dose Treg + Tcon (Dose escalation)
EXPERIMENTALParticipants receive low-dose Treg (1e6 cells/kg) and Tcon (3e6 cells/kg) with CD34+ HSPC.
Cohort 1A, Phase I: Low Dose Treg + Tcon (Dose escalation)
EXPERIMENTALParticipants receive low-dose Treg (1e6 cells/kg) and Tcon (1e6 cells/kg) with CD34+ HSPC.
Cohort 2, Phase 1: Mid Dose Treg + Tcon (Dose escalation)
EXPERIMENTALParticipants receive low-dose Treg (3e6 cells/kg), Tcon (1e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
Cohort 2A, Phase I: Mid Dose Treg + Tcon (Dose escalation)
ACTIVE COMPARATORParticipants receive low-dose Treg (up to 3e6 cells/kg), Tcon (3e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
Cohort 3, Phase I: High Dose Treg + Tcon (Dose escalation)
EXPERIMENTALParticipants receive high-dose Treg (3e6 cells/kg), Tcon (3e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
Cohort 3A, Phase I: High Dose Treg + Tcon (Dose escalation)
EXPERIMENTALParticipants receive high-dose Treg (1e6 cells/kg), Tcon (1e6 cells/kg), and CD34+ HSPC following a conditioning regimen.
Phase 2: Myeloablative HCT Control
ACTIVE COMPARATORParticipants receive standard myeloablative conditioning with CD34+ HSPC and no experimental Treg or Tcon.
Phase 2 Treg + Tcon with Immunosuppression
EXPERIMENTALParticipants receive Treg and Tcon therapy with immunosuppressive drugs following myeloablative conditioning.
Phase 2 Treg + Tcon without Immunosuppression
EXPERIMENTALParticipants receive Treg and Tcon therapy without immunosuppressive drugs following myeloablative conditioning.
Interventions
Purified CD34+ hematopoietic progenitor cells used in transplantation.
Highly purified CD4+CD25+CD127-FoxP3+ regulatory T cells to reduce graft-versus-host disease.
Conventional CD3+ T cells used for immune reconstitution and graft enhancement.
Chemotherapy or total body irradiation used before hematopoietic cell transplantation.
Eligibility Criteria
You may qualify if:
- Patients with the following diseases that are histopathologically confirmed are eligible
- Acute leukemia, primary refractory or beyond CR1, or minimal residual disease (MRD) positivity.
- High risk acute myeloid leukemia in CR1 with any of the following features:
- Complex karyotype(≥3 clonal chromosomal abnormalities)
- Any of the following high risk chromosomal abnormalities:
- Monosomal karyotype (-5, 5q-, -7, 7q-)
- t(11q23), t(9;11), inv(3), t(3;3) t(6;9) t(9;22)
- Normal karyotype with fms-like tyrosine kinase 3 (FLT3)-ITD mutation
- Other high risk features as determined by molecular studies, or clinical presentation as assessed by the treating physician
- Chronic myelogenous leukemia (accelerated, blast or second chronic phase)
- Myelodysplastic syndromes
- Myeloproliferative syndromes
- Non-Hodgkin lymphoma with poor risk features not suitable for autologous HCT
- Age ≥18 yo and ≤ 60 yo for patients in Cohort 1 only. At the start of Cohort 2A and beyond, eligibility will be expanded to allow pediatric patients age ≥ 13 yo.
- Cardiac ejection fraction ≥ 45%
- +6 more criteria
You may not qualify if:
- Seropositive for any of the following:
- HIV ab; hepatitis B sAg; hepatitis C ab
- Prior myeloablative therapy or hematopoietic cell transplant
- Candidate for autologous transplant
- HIV positive
- Active uncontrolled bacterial, viral or fungal infection, defined as currently taking antimicrobial therapy and progression of clinical symptoms.
- Uncontrolled central nervous system (CNS) disease involvement
- Pregnant or a lactating female
- Positive serum or urine beta human chorionic gonadotropin (HCG) test in females of childbearing potential within 3 weeks of registration
- Psychosocial circumstances that preclude the patient being able to go through transplant or participate responsibly in follow up care
- Age ≥13 yo and ≤ 75 years
- Karnofsky performance status of ≥ 70% defined by institutional standards
- Seronegative for HIV 1 RNA (polymerase chair reaction (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 for hepatitis C; negative for the Treponema pallidum antibody Syphilis 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 pallidum antibody tests are positive, donors must:
- Be evaluated and show no evidence of syphilis infection of any stage by physical exam and history
- Have completed effective antibiotic therapy to treat syphilis
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Stanford Universitylead
- National Institutes of Health (NIH)collaborator
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
Study Sites (1)
Stanford University School of Medicine Palo Alto, California, United States
Palo Alto, California, 94305, United States
Related Publications (3)
Meyer EH, Pavlova A, Villar-Prados A, Bader C, Xie B, Muffly L, Kim P, Sutherland K, Bharadwaj S, Dahiya S, Frank M, Arai S, Johnston L, Miklos D, Rezvani A, Shiraz P, Sidana S, Shizuru J, Weng WK, Agrawal V, Putnam A, Fernhoff N, Tamarisis J, Lu Y, Pawar RD, McClellan JS, Lowsky R, Negrin RS. Donor regulatory T-cell therapy to prevent graft-versus-host disease. Blood. 2025 May 1;145(18):2012-2024. doi: 10.1182/blood.2024026446.
PMID: 39792934DERIVEDBader CS, Pavlova A, Lowsky R, Muffly LS, Shiraz P, Arai S, Johnston LJ, Rezvani AR, Weng WK, Miklos DB, Frank MJ, Tamaresis JS, Agrawal V, Bharadwaj S, Sidana S, Shizuru JA, Fernhoff NB, Putnam A, Killian S, Xie BJ, Negrin RS, Meyer EH. Single-center randomized trial of T-reg graft alone vs T-reg graft plus tacrolimus for the prevention of acute GVHD. Blood Adv. 2024 Mar 12;8(5):1105-1115. doi: 10.1182/bloodadvances.2023011625.
PMID: 38091578DERIVEDMeyer EH, Laport G, Xie BJ, MacDonald K, Heydari K, Sahaf B, Tang SW, Baker J, Armstrong R, Tate K, Tadisco C, Arai S, Johnston L, Lowsky R, Muffly L, Rezvani AR, Shizuru J, Weng WK, Sheehan K, Miklos D, Negrin RS. Transplantation of donor grafts with defined ratio of conventional and regulatory T cells in HLA-matched recipients. JCI Insight. 2019 May 16;4(10):e127244. doi: 10.1172/jci.insight.127244. eCollection 2019 May 16.
PMID: 31092732DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Everett Meyer
- Organization
- Stanford University
Study Officials
- PRINCIPAL INVESTIGATOR
Everett Meyer
Stanford University
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associate Professor of Medicine
Study Record Dates
First Submitted
August 6, 2012
First Posted
August 8, 2012
Study Start
February 9, 2012
Primary Completion
December 20, 2023
Study Completion
December 20, 2023
Last Updated
August 19, 2025
Results First Posted
August 19, 2025
Record last verified: 2025-08
Data Sharing
- IPD Sharing
- Will not share