PHASE II STUDY OF TOTAL MARROW AND LYMPHOID IRRADIATION (TMLI) ADMINISTERED IN COMBINATION WITH A REDUCED-INTENSITY REGIMEN BASED ON FLUDARABINE AND MELPHALAN AS 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. (For adults, only participants with mild cognitive abilities may use a legally authorized representative).
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.
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.
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 MUGA or echocardiogram.
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.
Age: 50 years or HCT-CI pre-transplant score 3 or any other condition that precludes the use of a fully myeloablative conditioning regimen.
Karnofsky's performance status 70%
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).
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).
The time elapsed since the end of the last induction or re-induction cycle must be greater than or equal to 14 days.
Total bilirubin 1.5 mg/dL x Upper Limit of Normality (ULN) OR 3 x ULN for Gilbert's disease.
Serum glutamic-oxaloacetic transaminase (SGOT) & serum glutamic-pyruvic transaminase (SGPT) 5 x ULN.
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.
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.
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 MUGA or echocardiogram.
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.
Age: 50 years or HCT-CI pre-transplant score 3 or any other condition that precludes the use of a fully myeloablative conditioning regimen.
Karnofsky's performance status 70%
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).
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).
The time elapsed since the end of the last induction or re-induction cycle must be greater than or equal to 14 days.
Total bilirubin 1.5 mg/dL x Upper Limit of Normality (ULN) OR 3 x ULN for Gilbert's disease.
Serum glutamic-oxaloacetic transaminase (SGOT) & serum glutamic-pyruvic transaminase (SGPT) 5 x ULN.
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 fludarabine or melphalan.
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 fludarabine or melphalan.
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 TMLI administered, in combination with fludarabine and melphalan for (AHSCT) in patients with risk MDS or AML who are not candidates for myeloablative conditions, as assessed by 2-year progression-free survival.
PALABRAS CLAVE
acute myeloid leukemia, hematopoietic, hematopoietic stem cell transplant, leukemia, myelodysplastic syndrome, ph + acute lymphoblastic leukemia, reduced intensity conditioning, stem cell
