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.
⁃ 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.