GVHDPhase 1NCT07302776
TACrolimus Targeted Immunosuppression Cessation in ALlogeneic HCT
A Phase 1 study testing Tacrolimus and Early Tacrolimus Taper Strategy in people with GVHD and Hematopoietic Cell Transplantation (HCT), run by Stanford University at 1 site in United States.
Trial summary
The purpose of this study is to test the feasibility and safety of early cessation of tacrolimus following allogeneic hematopoietic cell transplantation (HCT). Post-HCT tacrolimus is given to prevent graft-vs-host-disease (GVHD), but with the use of post-transplant cyclophosphamide (PTCy), the modern approach to GVHD… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- GVHD, Hematopoietic Cell Transplantation (HCT), Acute Myeloid Leukemia (AML)
- What is being tested?
- Tacrolimus and Early Tacrolimus Taper Strategy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jul 2026to Feb 2028
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Eligible diseases:
- Acute myeloid leukemia (AML) in complete remission (CR), CR with incomplete hematologic recovery (CRi), or MLFS.
- Myelodysplasic syndrome (MDS) myelodysplastic syndromes eligible for alloHSCT based on IPSS-M of intermediate or higher, or IPSS-R of intermediate or higher, or refractory disease to standard growth factor or hypomethylating agent-based therapy
- Myelofibrosis (MF)
- Chronic myeloid leukemia (CML) in chronic phase with a prior history of accelerated phase or blast crisis or CML in chronic phase refractory to standard TKI therapy
- Chronic myelomonocytic leukemia (CMML)
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- Age ≥ 18 and ≤ 80 years at the time of enrollment.
- Planned for first myeloablative or reduced intensity allogenic transplant using a conditioning regimen listed in Appendix B.
- Has a related or unrelated donor available who is 8/8 HLA match at HLA-A, -B, -C, and -DRB1, all typed using DNA-based high-resolution methods.
- Estimated glomerular filtration rate (eGFR) ≥ 50 mL/minute or creatinine < 2 mg/dL.
- Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27% by echocardiogram or radionuclide scan (MUGA).
- Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50%.
- Total bilirubin < 2 times upper limit of normal (ULN) (patients with Gilbert's syndrome may be included once hemolysis has been excluded).
- Karnofsky Performance Score ≥70%
- Negative serum or urine beta-HCG test in females of childbearing potential (FCBP) within 3 weeks of enrollment.
- A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
- -Ability to understand and the willingness to provide written informed consent.
Who cannot join
- Prior allogeneic HCT.
- Planned donor lymphocyte infusion (DLI).
- Recipient positive anti-donor HLA antibodies against a mismatched allele in the selected donor determined by either:
- Positive crossmatch test of any titer (by complement-dependent cytotoxicity or flow cytometric testing), or
- Presence of anti-donor HLA antibody to any of the following HLA loci: HLA-A, -B, -C, -DRB1, -DQB1, -DQA1, -DPB1, or -DPA1, with mean fluorescence intensity (MFI) >1000 by solid phase immunoassay.
- Uncontrolled bacterial, viral, or fungal infections at time of enrollment including known, active tuberculosis infection.
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- Seropositive for HIV-1 or -2, HTLV-1 or -2, Hepatitis B sAg, and/or Hepatitis C antibody.
- History of hepatitis B or hepatitis C is permitted if viral load is undetectable per quantitative PCR and/or NAT.
- Known allergy or hypersensitivity to planned GVHD prophylactic medications including PTCy, tacrolimus
- Any uncontrolled autoimmune disease requiring active immunosuppressive treatment.
- Concurrent malignancy diagnosed within 12 months of enrollment, except non-melanoma skin cancers or other early-stage solid tumors that have been curatively resected or treated to curative intent. Patients with history of low grade concurrent blood cancers that are controlled will be eligible.
- Females of childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use effective forms of birth control or abstinence for one year after transplantation.
- (FCBP definition: A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
- -Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the recipient's safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results.
- All subject files must include supporting documentation to confirm subject eligibility.
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
Stanford University
Palo Alto, California, 94304
Kelly Chyan, 650-625-8130, kchyan@stanford.edu
Vanessa Kennedy, MD
About this study
Official title: TACTICAL: TACrolimus Targeted Immunosuppression Cessation in ALlogeneic HCT
The purpose of this study is to test the feasibility and safety of early cessation of tacrolimus following allogeneic hematopoietic cell transplantation (HCT). Post-HCT tacrolimus is given to prevent graft-vs-host-disease (GVHD), but with the use of post-transplant cyclophosphamide (PTCy), the modern approach to GVHD prevention, GVHD rates have reduced markedly.
- Conditions
- GVHD, Hematopoietic Cell Transplantation (HCT), Acute Myeloid Leukemia (AML), Myelodysplastic Syndromes, Myelofibrosis (MF), Chronic Myeloid Leukemia (CML)
- Being tested
- Tacrolimus, Early Tacrolimus Taper Strategy
- Keywords
- Post-Hematopoietic Cell Transplant (HCT) tacrolimus, hematopoietic cell transplantation (HCT)
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Primary Myelofibrosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myelomonocytic, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TacrolimusDrug
Tacrolimus is initiated on Day 5 post-HCT and transitioned to oral dosing once therapeutic levels are achieved. Oral tacrolimus is given in 0.5 mg increments up to twice daily. Levels are monitored several times weekly to target a trough of 5-10 ng/mL.
Early Tacrolimus Taper StrategyOther
Eligible participants begin a taper on Day 60 (±5 days), reducing the tacrolimus dose by ~20% weekly, rounded to 0.5 mg, with planned discontinuation by Day 88 (±5 days). Tapering stops if significant acute GVHD develops or if unsafe.
| Study group | Role | What they receive |
|---|---|---|
| Risk-Adapted Early Tacrolimus Taper Strategy | Experimental | Initial tacrolimus dosing will be as per Standard of Care protocol. Tacrolimus is initiated at day 5 post-HCT at with initial dosing as described in Section 6.2.3, and converted to oral formulation as soon as appropriate level is achieved and the patient are able to tolerate oral dosing. Oral tacrolimus is dosed in 0.5mg increments up to two times daily. Tacrolimus levels are assessed up to three times weekly in the inpatient or outpatient setting starting 1 - 3 days after initiation to target a level of 5 - 10 ng/mL. Trough levels will be assessed as close to 12 (twice daily dosing) or 24 (daily dosing) hours as feasible after most recent dose.
Starting on day 60, patients on Stratum A will taper tacrolimus by approximately 20% of pre-taper dose per week, rounded to the nearest 0.5 mg. Participants who meet criteria and will be completely off tacrolimus by day 88 (+/- 5 days). Receives: Drug: Tacrolimus; Other: Early Tacrolimus Taper Strategy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Feasibility of Early Tacrolimus Discontinuation
Proportion of patients who are low risk for acute graft-versus-host disease (aGVHD) who are able to discontinue tacrolimus by day 88 and who do not develop moderate to severe aGVHD by day 180.
Measured: Day 0 through Day 180 post-transplant
Secondary outcomes (8)
Incidence and Severity of Chronic Graft-Versus-Host Disease
Proportion of participants who develop chronic graft-versus-host disease, reported as all grades and severe chronic graft-versus-host disease.
Measured: Through 1 year after transplantation
Incidence of Non-Relapse Mortality
Incidence of death without relapse of the underlying disease.
Measured: 1 year post-HCT
Incidence of Disease Relapse
Proportion of participants who experience relapse of their underlying disease.
Measured: Through 1 year after transplantation
Overall Survival
Survival from the time of transplantation to death from any cause.
Measured: Through 1 year after transplantation
Relapse-Free Survival
Time from transplantation to relapse of the underlying disease or death from any cause.
Measured: Through 1 year after transplantation
Graft-Versus-Host Disease-Free, Relapse-Free Survival
Time to the first occurrence of grade III through IV acute graft-versus-host disease, chronic graft-versus-host disease requiring systemic therapy, relapse, or death.
Measured: Through 1 year after transplantation
Incidence and Severity of Infectious Complications
Proportion of participants who develop infectious complications, reported as all grades, grade 2 through 3, and grade 3.
Measured: Through 1 year after transplantation
Incidence and Severity of Acute Graft-Versus-Host Disease
Proportion of participants who develop acute graft-versus-host disease, reported as all grades, grade II through IV, and grade III through IV.
Measured: Through Day 180 after transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2025
- Study start21 Jul 2026
- Primary completionFeb 2028 (estimated)
- Study completionFeb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GVHDStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe 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
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- Eurofins Viracor Biopharma
- Responsible party
- Sponsor
- Investigators
- Vanessa Kennedy, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07302776
- Sponsor's protocol ID
- IRB-82367
- Other IDs
- NCI-2026-03473
- Status last verified
- Aug 2026
- First submitted
- 11 Dec 2025
- Last updated
- 17 Aug 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No