Preparation for bone marrow transplant through the combined use of chemo and radiotherapy (intensive or myeloablative: eliminates stem cells)

Trial details

Who runs it

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

Trial code

EU 2024-514484-25-00

Record updated

2025. október 24.

Original description

The antitumor activity of the conditioning regimen with TMLI, cyclophosphamide and etoposide followed by AHSCT will be evaluated by means of the progression-free survival (PFS) at 2 years after a safety-lead phase.Read full original descriptionShow less

PHASE II STUDY OF TOTAL MARROW AND LYMPHOID IRRADIATION (TMLI) ADMINISTERED IN COMBINATION WITH A MYELOABLATIVE REGIMEN BASED ON CYCLOPHOSPHAMIDE AND ETOPOSIDE AS A CONDITIONING FOR ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (AHSCT) IN PATIENTS WITH HIGH-RISK MYELODYSPLASTIC SYNDROME OR ACUTE MYELOID LEUKEMIA

The antitumor activity of the conditioning regimen with TMLI, cyclophosphamide and etoposide followed by AHSCT will be evaluated by means of the progression-free survival (PFS) at 2 years after a safety-lead phase.

Inclusion: The participant has the ability and willingness to sign the informed consent document; Pulmonary function tests: forced expiratory volume in one second (FEV1) and Carbon Monoxide Diffusion Capacity (DLCO) (adjusted for Hb) ≥ 50% from expected normal value; 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; ECG showing no ischemic changes or clinically significant arrhythmia; 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; The time elapsed since the end of the last induction or reinduction cycle must be greater than or equal to 14 days; Age ≥18 to ≤50 years; Karnofsky’s performance status should be ≥70%; 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); 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; Total bilirubin ≤ 1.5 x ULN OR 3 x ULN for Gilbert's disease; SGOT & SGPT ≤ 5 x LSN; Serum creatinine ≤ 1.3 mg/dL or creatinine clearance measured ≥ 80 mL/min for 24 hours of urine collection; Women of childbearing age only: Negative urine or serum pregnancy test.

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

EU CTIS 2024-514484-25-00