NIPH Clinical Trials Search

Phase I Trial Evaluating the Safety of Trametinib in Combination with Tacrolimus and Methotrexate for Graft-Versus-Host Disease Prophylaxis After Allogeneic Hematopoietic Stem Cell Transplantation

Basic Information

Recruitment status	Recruiting
Health condition(s) or Problem(s) studied	Patients undergoing allogeneic bone marrow or peripheral blood stem cell transplantation
Date of first enrollment	21/05/2026
Target sample size	4
Countries of recruitment
Study type	Interventional
Intervention(s)	Trametinib 2.0 mg once daily Administered orally from Day 0 (day of transplantation) for up to 28 days Taken in a fasting state (approximately 2 hours after lunch) Dose modification: temporary interruption and dose reduction to 1.0 mg allowed; no dose escalation Tacrolimus Initiated on Day -1 Start with intravenous administration; switch to oral as needed Target trough level: 5-15 ng/mL Methotrexate 5 mg/m2 IV on Days 1, 3, 6, and 11 Can be reduced or skipped depending on patient condition

Outcome(s)

Primary Outcome	Number and severity of adverse events
Secondary Outcome	Presence or absence of neutrophil and platelet engraftment Presence or absence of engraftment syndrome Occurrence of acute GVHD Immune reconstitution assessed by peripheral blood lymphocyte counts Occurrence of infections

Key inclusion & exclusion criteria

Age minimum	>= 18age old
Age maximum	Not applicable
Gender
Include criteria	1. Age >= 18 years. 2. Written informed consent must be obtained from the participant prior to enrollment. 3. Patients scheduled to undergo allogeneic bone marrow transplantation or peripheral blood stem cell transplantation for one of the following diseases: - Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) with no blasts in peripheral blood and <5% blasts in bone marrow. Therapy-related myeloid neoplasms are also eligible. - Myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) with no blasts in peripheral blood and <10% blasts in bone marrow. (For MDS, <5% and 5-10% blasts do not differ in prognosis; therefore, up to 10% is permitted.) Therapy-related myeloid neoplasms are also eligible. 4. Patients scheduled to receive a myeloablative or reduced-intensity conditioning regimen. 5. Patients who have an eligible bone marrow or peripheral blood stem cell donor who meets domestic regulations (MHLW notifications, HSCT guidelines, Japan Marrow Donor Program rules) and institutional donor criteria, and who has provided consent to donate: - Related donor: high-resolution HLA typing must show at least 7/8 match at HLA-A, -B, -C, and -DRB1. - Unrelated donor: high-resolution HLA typing must show 7/8 or 8/8 match at HLA-A, -B, -C, and -DRB1. 6. Cardiac function preserved: left ventricular ejection fraction (LVEF) >= 50%. 7. Renal function preserved: estimated creatinine clearance >= 60 mL/min by eGFR or 24-hour creatinine clearance. 8. Pulmonary function preserved: hemoglobin-corrected DLCO >= 40% and FEV1 >= 50% of predicted. 9. Hepatic function preserved: AST/ALT < 3 x institutional upper limit of normal; total bilirubin < 2 mg/dL (excluding Gilbert's syndrome or hemolytic disease). 10. ECOG performance status 0-1. 11. Reproductive requirements: - Women who are not postmenopausal for >=1 year or who have not undergone surgical sterilization must agree to use two effective contraceptive methods or abstain from heterosexual intercourse from consent to 6 months after transplantation. - Men (including those surgically sterilized) with partners of childbearing potential must agree to use effective barrier contraception or abstain from heterosexual intercourse from consent to 6 months after transplantation.
Exclude criteria	1. Prior allogeneic hematopoietic stem cell transplantation. 2. Active malignant infiltration of the central nervous system (CNS). 3. Secondary AML arising from myeloproliferative neoplasms (MPN) or overlap syndromes (including CMML and MDS/MPN). Note: Secondary AML evolving from MDS is eligible. 4. Primary myelofibrosis. 5. Uncontrolled infections, including bacterial, viral, or fungal infections under treatment that show progression or no clinical improvement. 6. Active or inadequately treated latent tuberculosis infection. 7. Clinically significant effusions (ascites, pleural effusion, pericardial effusion) that impair methotrexate excretion or represent a contraindication to methotrexate. 8. HIV-positive patients with detectable viral load. HIV-positive patients receiving antiviral therapy with undetectable viral load are eligible. 9. Uncontrolled hepatitis B or hepatitis C infection. The following cases are allowed: HBV antibody positive with HBV-DNA below detection and receiving antiviral prophylaxis; HCV antibody positive with HCV RNA below detection, regardless of treatment history. 10. Arterial or venous thrombosis within 6 months prior to registration (including DVT, pulmonary embolism, stroke, myocardial infarction), or severe cardiac diseases, such as: NYHA Class III or IV heart failure; uncontrolled angina; severe uncontrolled ventricular arrhythmias; acute ischemic ECG findings. Catheter-related DVT does not constitute exclusion. 11. Ocular diseases requiring treatment, including retinal vein occlusion, retinal pigment epithelial detachment, retinal detachment, or uveitis. 12. Pregnant or breastfeeding women. 13. Serious medical or psychiatric conditions that may interfere with the participant's ability to complete the study. 14. Active double cancers (exceptions permitted: completely resected basal cell carcinoma, carcinoma in situ, intramucosal cancer, superficial bladder cancer, or other malignancies with no recurrence for >=5 years). 15. Planned use of antithymocyte globulin (ATG) or alemtuzumab in the conditioning regimen. 16. Planned donor lymphocyte infusion (DLI). 17. History of trametinib use. 18. Use of immune checkpoint inhibitors (PD-1, PD-L1, CTLA-4 modulators, etc.) within 6 months before conditioning. 19. Cases where an HLA 7/8-matched donor meets either of the following: presence of donor-specific antibodies (DSA) against mismatched HLA alleles; prior use of a desensitization protocol. 20. Participation in another clinical trial involving investigational products during trametinib administration. 21. Any other condition judged by the principal investigator or sub-investigator to make the patient unsuitable for study participation.