ETOPOSIDE for High-risk myelodysplastic syndrome | Acute myeloid leukemia

Inclusion criteria

• {"criterion_text":"- The participant has the ability and willingness to sign the informed consent document\n- 3.\tPulmonary function tests: forced expiratory volume in one second (FEV1) and Carbon Monoxide Diffusion Capacity (DLCO) (adjusted for Hb) ≥ 50% from expected normal value\n- Patients should undergo cardiac evaluation with an electrocardiogram showing no ischemic changes or clinically relevant arrhythmia, and a ≥50% ejection fraction established by Multi-Gated Acquisiton Scan (MUGA) or echocardiogram\n- ECG showing no ischemic changes or clinically significant arrhythmia\n- Men and women of childbearing potential agree to use appropriate contraceptives (hormonal or barrier contraception or abstinence) prior to study entry and for six months following the duration of study participation\n- The time elapsed since the end of the last induction or reinduction cycle must be greater than or equal to 14 days\n- Age ≥18 to ≤50 years\n- Karnofsky’s performance status should be ≥70%\n- Patients with myelodysplastic syndrome/acute myeloid leukemia or acute myeloid leukemia with relapsed/refractory active disease, or in complete remission or morphologic leukemia-free state with evidence of measurable residual disease as assessed by multiparameter flow cytometry (≥ 0,1%) or next-generation sequencing (in the case of FLT3-ITD-mutated AML)\n- All candidates for this study must have an HLA (A, B, C, DR) identical siblings who are willing to donate bone marrow or peripheral blood hematopoietic progenitors or an 8/8 matched unrelated donor. A single allele mismatch in A, B, C or DRB1 shall be allowed\n- Total bilirubin ≤ 1.5 x ULN OR 3 x ULN for Gilbert's disease\n- SGOT & SGPT ≤ 5 x LSN\n- Serum creatinine ≤ 1.3 mg/dL or creatinine clearance measured ≥ 80 mL/min for 24 hours of urine collection\n- Women of childbearing age only: Negative urine or serum pregnancy test"}

Exclusion criteria

• {"criterion_text":"- Patients who have received a previous autologous (within the last year) or allogeneic transplant (at any time) are excluded\n- Subjects who, in the opinion of the investigator, may not be able to meet the safety control requirements of the study\n- Previous radiation therapy, which would preclude the use of TMLI\n- Plans during the trial to receive any other investigational (non-trial-related) agents\n- Uncontrolled disease, including ongoing or active infection\n- History of allergic reactions attributed to compounds of chemical or biological composition similar to cyclophosphamide or etoposide\n- Patients with other active malignancies are not eligible for this study, other than the malignancies discussed\n- Patients with a psychological or medical condition that the patient's physician deems unacceptable to proceed with allogeneic hematopoietic stem cell transplantation\n- Women who plan to become pregnant or breastfeed during the trial\n- Patients who do not agree to practice effective forms of contraception"}

Primary endpoints

• {"endpoint_text":"- Toxicity, which will be graded on both the Bearman Scale and the NCI CTCAE Scale v5.0\n- The evaluation of 2-year PFS. PFS will be defined as time from the start of treatment to the ate of death, disease relapse/progression, or date of last follow-up, and estimated using the Kaplan-Meier method","definition_or_measurement_approach":"- Graded on both the Bearman Scale and the NCI CTCAE Scale v5.0\n- PFS defined as time from the start of treatment to the date of death, disease relapse/progression, or date of last follow-up; estimated using the Kaplan-Meier method"}

Secondary endpoints

• {"endpoint_text":"- Overall survival (OS): patients are considered a failure for this endpoint if they die, regardless of the cause. The time to this event is the time from the start of protocol therapy to death, or the last follow-up, whichever comes first\n- Cumulative incidence (CI) of recurrence/progression: The event is relapse/progression either extramedullary (EM) or at bone marrow (BM) (date and place). The time to this event is measured from the start of therapy. Death without relapse/progression is considered a competing risk. Surviving patients with no history of relapse/progression are censored at the time of last follow-up\n- Complete remission (CR) rate at day 30 post-transplant: The event is whether or not the patient has a documented CR on day 30\n- Non-relapse mortality (NRM2. NRM is measured from the start of therapy until non-disease-related death, or the last follow-up, whichever comes first\n- Measurable residual disease (MRD): MRD monitoring assessed by multiparameter flow cytometry at 30, 90, 180, 360, 575 days, and 2 years post-transplant\n- Incidence of infection: Microbiologically documented infections will be reported by site of illness, date of onset, severity, and resolution, if applicable. This data will be captured through the case report form and will be collected from day 0 to 100 days after transplantation\n- Toxicities/Adverse Events: The Bearman Scale (non-hematologic) and CTCAE v. 5.0 (hematologic) will be employed. Dose/dose-volume toxicity characterization across organs will be assessed\n- Acute graft-versus-host disease (GVHD) grades 2-4 and 3-4:. The endpoint will be assessed from day 0 to 100 days post-transplant\n- Chronic graft-versus-host disease (GVHD): Chronic graft-versus-host disease is graded according to the NIH consensus staging. The first day of onset of chronic GVHD will be used to calculate cumulative incidence curves","definition_or_measurement_approach":"- OS measured from start of protocol therapy to death or last follow-up\n- CI of recurrence/progression measured from start of therapy; death without relapse considered competing risk; censoring at last follow-up for survivors without relapse/progression\n- CR rate at day 30 post-transplant assessed by documented CR on day 30\n- NRM measured from start of therapy until non-disease-related death or last follow-up\n- MRD assessed by multiparameter flow cytometry at specified days (30,90,180,360,575 and 2 years)\n- Infections: microbiologically documented, reported by site, date, severity, resolution; collected day 0 to day 100 post-transplant via CRF\n- Toxicities/AEs: Bearman Scale for non-hematologic and CTCAE v5.0 for hematologic; dose/dose-volume characterization across organs\n- Acute GVHD grades 2-4 and 3-4 assessed from day 0 to day 100 post-transplant\n- Chronic GVHD graded per NIH consensus staging; onset date used for cumulative incidence curves"}

Spain

Earliest CTIS Part Ii Submission Date

14-11-2024

Latest Decision Or Authorization Date

24-10-2025

Processing Time Days

344

Number Of Sites

1

Number Of Participants

49

Primary sponsor

Full Name

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Spain