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
ESTADO CLÍNICO
Reclutando
FASE/S DEL ENSAYO
Fase II
PATOLOGÍA
Leucemia mieloide aguda, Síndromes mielodisplásicos, Terapia celular y T-CARs, Trasplante de progenitores hematopoyéticos, Linfoma, Leucemia
FECHA DE APERTURA
Noviembre, 2024
FECHA DE CIERRE
,
CRITERIOS DE INCLUSIÓN
The participant has the ability and willingness to sign the informed consent document
3. 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
Karnofskys 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
3. 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
Karnofskys 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
CRITERIOS DE EXCLUSIÓN
Patients who have received a previous autologous (within the last year) or allogeneic transplant (at any time) are excluded
Subjects who, in the opinion of the investigator, may not be able to meet the safety control requirements of the study
Previous radiation therapy, which would preclude the use of TMLI
Plans during the trial to receive any other investigational (non-trial-related) agents
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
Women who plan to become pregnant or breastfeed during the trial
Patients who do not agree to practice effective forms of contraception
Subjects who, in the opinion of the investigator, may not be able to meet the safety control requirements of the study
Previous radiation therapy, which would preclude the use of TMLI
Plans during the trial to receive any other investigational (non-trial-related) agents
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
Women who plan to become pregnant or breastfeed during the trial
Patients who do not agree to practice effective forms of contraception
DESCRIPCIÓN
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.
PALABRAS CLAVE
acute myeloid leukemia, hematopoietic, hematopoietic stem cell transplant, leukemia, myelodysplastic syndrome, ph + acute lymphoblastic leukemia, stem cell
