TACTICAL: TACrolimus Targeted Immunosuppression Cessation in ALlogeneic HCT
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Safety and Feasibility of Early Tacrolimus Discontinuation
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
- •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.
排除标准
- •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.
- •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.
研究组 & 干预措施
Risk-Adapted Early Tacrolimus Taper Strategy
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).
干预措施: Tacrolimus (Drug)
Risk-Adapted Early Tacrolimus Taper Strategy
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).
干预措施: Early Tacrolimus Taper Strategy (Other)
结局指标
主要结局
Safety and Feasibility of Early Tacrolimus Discontinuation
时间窗: Day 0 through Day 180 post-transplant
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.
次要结局
- Relapse-Free Survival(Through 1 year after transplantation)
- Incidence and Severity of Chronic Graft-Versus-Host Disease(Through 1 year after transplantation)
- Incidence of Non-Relapse Mortality(1 year post-HCT)
- Incidence of Disease Relapse(Through 1 year after transplantation)
- Overall Survival(Through 1 year after transplantation)
- Incidence and Severity of Acute Graft-Versus-Host Disease(Through Day 180 after transplantation)
- Graft-Versus-Host Disease-Free, Relapse-Free Survival(Through 1 year after transplantation)
- Incidence and Severity of Infectious Complications(Through 1 year after transplantation)