FLUDARABINE PHOSPHATE 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. (For adults, only participants with mild cognitive abilities may use a legally authorized representative)."}
• {"criterion_text":"- Serum creatinine ≤ 1.3 mg/dL or creatinine clearance measured ≥ 80 mL/min for 24 hours of urine collection."}
• {"criterion_text":"- Women of childbearing age only: Negative urine or serum pregnancy test."}
• {"criterion_text":"- 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. If a woman becomes pregnant or suspects she is pregnant while participating in the trial, she should inform her treating physician immediately."}
• {"criterion_text":"- Pulmonary function tests: forced expiratory volume in one second (FEV1) and Carbon Monoxide Diffusion Capacity (DLCO) (adjusted for Hb) ≥ 50% from expected normal value."}
• {"criterion_text":"- Patients should undergo cardiac evaluation with an electrocardiogram showing no ischemic changes or clinically relevant arrhythmia, and a ≥50% ejection fraction established by MUGA or echocardiogram."}
• {"criterion_text":"- Documented (signed) informed consent. The patient, family member, and doctor of the transplant staff (doctor, nurse, and social worker) meet at least once before the transplant procedure begins. During this meeting, all relevant information regarding the risks and benefits to the donor and recipient will be presented. Alternative treatment modalities will be discussed. The risks are explained in detail in the attached consent forms."}
• {"criterion_text":"- Age: ≥ 50 years or HCT-CI pre-transplant score ≥ 3 or any other condition that precludes the use of a fully myeloablative conditioning regimen."}
• {"criterion_text":"- Karnofsky's performance status ≥ 70%"}
• {"criterion_text":"- Patients with myelodysplastic syndrome/acute myeloid leukemia (per ICC 2022 criteria) or acute myeloid leukemia with relapsed/refractory active disease (i.e. ≥5% bone marrow blasts), or in complete remission (CR) or morphologic leukemia-free state (MLFS) 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)."}
• {"criterion_text":"- All candidates for this study must have an 8/8 HLA-identical (A, B, C, DR) or an unrelated donor with at least 8/8 HLA matching. A single allele mismatch in A, B, C, DR or DQ and a KIR mismatch in C shall be allowed. All combinations of donor/recipient ABO blood types are acceptable; as even major ABO compatibilities can be treated using a variety of techniques (red blood cell exchange or plasma exchange)."}
• {"criterion_text":"- The time elapsed since the end of the last induction or re-induction cycle must be greater than or equal to 14 days."}
• {"criterion_text":"- Total bilirubin ≤ 1.5 mg/dL x Upper Limit of Normality (ULN) OR 3 x ULN for Gilbert's disease."}
• {"criterion_text":"- Serum glutamic-oxaloacetic transaminase (SGOT) & serum glutamic-pyruvic transaminase (SGPT) ≤ 5 x ULN."}

Exclusion criteria

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

Primary endpoints

• {"endpoint_text":"- The primary endpoint for the primary patient safety segment of this study is toxicity. Toxicity will be graded on both the Bearman Scale (Appendix I) and the NCI CTCAE Scale and v5.0 (Appendix II).","definition_or_measurement_approach":"Toxicity graded using the Bearman Scale and NCI CTCAE v5.0."}
• {"endpoint_text":"- The primary endpoint is 2 year progression-free survival (PFS). PFS will be defined as time from the start of treatment to the date of death, disease relapse/progression, or date of last follow-up, and estimated using the Kaplan-Meier method. Patients are considered a failure for this endpoint if they die or if they relapse/progress. The time to this event is the time from the start of protocol therapy to death, relapse/progression, or the last follow-up, whichever comes first.","definition_or_measurement_approach":"PFS defined as time from start of treatment to death, relapse/progression, or last follow-up; estimated using Kaplan-Meier. Failure = death or relapse/progression."}

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.","definition_or_measurement_approach":"OS measured from start of protocol therapy to death or last follow-up; failure = death."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"CI measured from start of therapy; relapse/progression (EM or BM) is event; death without relapse/progression treated as competing risk; censor at last follow-up."}
• {"endpoint_text":"- Complete remission (CR) rate at day 30 post-transplant: The event is whether or not the patient has a documented CR on day 30. Time to event is measured from the day of infusion to the time of CR.","definition_or_measurement_approach":"CR assessed on day 30 post-transplant; time measured from day of infusion to CR."}
• {"endpoint_text":"- Non-relapse mortality (NRM): Patients are considered a failure for this endpoint if they die from causes other than relapse or progression. NRM is measured from the start of therapy until non-disease-related death, or the last follow-up, whichever comes first.","definition_or_measurement_approach":"NRM measured from start of therapy to non-disease-related death or last follow-up; failure = non-relapse death."}
• {"endpoint_text":"- Measurable residual disease (MRD): MRD monitoring assessed by multiparameter flow cytometry at 30, 90, 180, 360, 575 days, and 2 years post-transplant.","definition_or_measurement_approach":"MRD assessed by multiparameter flow cytometry at specified timepoints (30, 90, 180, 360, 575 days, and 2 years)."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Microbiologically documented infections reported by site, date, severity, resolution; collected via CRF from day 0 to day 100 post-transplant."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Toxicities graded with Bearman Scale (non-hematologic) and CTCAE v5.0 (hematologic); dose/dose-volume toxicity characterization across organs."}
• {"endpoint_text":"- Acute graft-versus-host disease (GVHD) grades 2-4 and 3-4: Acute graft-versus-host disease is classified according to the consensus classification. The first day of onset of acute GVHD to a certain degree will be used to calculate the cumulative incidence curves for that grade of GVHD. The endpoint will be assessed from day 0 to 100 days post-transplant.","definition_or_measurement_approach":"Acute GVHD graded per consensus classification; onset date used to calculate cumulative incidence; assessed from day 0 to day 100 post-transplant."}
• {"endpoint_text":"- 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":"Chronic GVHD graded per NIH consensus staging; onset used to calculate cumulative incidence."}

Spain

Earliest CTIS Part Ii Submission Date

10-10-2024

Latest Decision Or Authorization Date

20-10-2025

Processing Time Days

375

Number Of Sites

1

Number Of Participants

46

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