Patients undergoing allogeneic bone marrow or peripheral blood stem cell transplantation Allogeneic Hematopoietic Stem Cell Transplantation
Conditions
Interventions
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 interru
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
C560077
Trametinib, Acute GVHD Prophylaxis, Tacrolimus and Methotrexate Combination, Post-ransplant Immune Reconstitution
Sponsors
Shindo Takero
Eligibility
Inclusion criteria
Inclusion 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 = 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 =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.
Exclusion criteria
Exclusion 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number and severity of adverse events | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
Contacts
Public ContactTakero Shindo
Hiroshima university hospital
Outcome results
None listed