A Multi-phase, Dose-Escalation followed by an Open-label, Randomized, Crossover Study of Oral ASTX030 (Cedazuridine and Azacitidine Given in Combination) Versus Subcutaneous Azacitidine in Subjects with Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), or Acute Myeloid Leukemia (AML)
ESTADO CLÍNICO
Reclutando
FASE/S DEL ENSAYO
Fase III
PATOLOGÍA
Leucemia linfática crónica y otros SLPC, Leucemia mieloide aguda, Neoplasias mieloproliferativas crónicas Philadelphia(-), Síndromes mielodisplásicos, Leucemia mieloide crónica, Linfoma, Leucemia
CENTRO INVESTIGADOR
H.G.U. Gregorio Marañón
INVESTIGADOR PRINCIPAL
Gabriela Rodriguez Macías
CENTRO INVESTIGADOR
MD Anderson Cancer Center Madrid
INVESTIGADOR PRINCIPAL
Adolfo De la Fuente
CENTRO INVESTIGADOR
H.U. La Paz
INVESTIGADOR PRINCIPAL
Maria Raquel de Paz Arias
FECHA DE APERTURA
Junio, 2025
FECHA DE CIERRE
,
CRITERIOS DE INCLUSIÓN
1. Must be 18 years
8. Able to swallow the number of capsules required within 10-mins and can tolerate 4 hours of fasting.
9. Life expectancy >= 12 weeks.
10. Follow contraceptive barrier requirements per protocol
11. Capable of giving legally effective informed consent. and willing to participate in the study.
2. Confirmed MDS or CMML and a candidate to receive and benefit from single-agent azacitidine according to French-American-British myelodysplastic syndrome subtypes: or MDS with intermediate-2 or high risk MDS according to the IPSS (Greenberg P, et al. Blood. 1997;89:2079-2088)
3. ECOG 0 or 1
4. Adequate organ function : a. Total or direct bilirubin 2 × ULN; AST/ SGOT and ALT/SGPT 2.5 × ULN. b. Calculated CrCl >50 mL/min by Cockcroft-Gault formula or other medically acceptable formulas.
5. For participants with prior allogeneic stem cell transplant, has no evidence of graft vs host disease and must be 3 weeks off systemic immunosuppressive therapy before study start.
6. No major surgery within 3 weeks before treatment initiation.
7. No cytotoxic chemotherapy (excluding hydroxyurea) within 4 weeks before treatment initiation
8. Able to swallow the number of capsules required within 10-mins and can tolerate 4 hours of fasting.
9. Life expectancy >= 12 weeks.
10. Follow contraceptive barrier requirements per protocol
11. Capable of giving legally effective informed consent. and willing to participate in the study.
2. Confirmed MDS or CMML and a candidate to receive and benefit from single-agent azacitidine according to French-American-British myelodysplastic syndrome subtypes: or MDS with intermediate-2 or high risk MDS according to the IPSS (Greenberg P, et al. Blood. 1997;89:2079-2088)
3. ECOG 0 or 1
4. Adequate organ function : a. Total or direct bilirubin 2 × ULN; AST/ SGOT and ALT/SGPT 2.5 × ULN. b. Calculated CrCl >50 mL/min by Cockcroft-Gault formula or other medically acceptable formulas.
5. For participants with prior allogeneic stem cell transplant, has no evidence of graft vs host disease and must be 3 weeks off systemic immunosuppressive therapy before study start.
6. No major surgery within 3 weeks before treatment initiation.
7. No cytotoxic chemotherapy (excluding hydroxyurea) within 4 weeks before treatment initiation
CRITERIOS DE EXCLUSIÓN
1. Active, uncontrolled gastric or duodenal ulcer.
4. Known positive for Hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months of screening
5. Life-threatening illness, uncontrolled medical condition or organ system dysfunction, or other reasons that, could compromise the participant's safety, interfere with the absorption or metabolism of ASTX030, or the integrity of study outcomes.
6.History of other malignancies, except certain adequately treated and/or controlled cancers, or early-stage cases not requiring therapy.
7. Extramedullary disease in MDS/MPN, including palpable hepatomegaly or splenomegaly
8. Prior treatment with > 1 cycle of decitabine or azacitidine
9. Treated with any investigational therapy within 2 weeks, or 5 half-lives, whichever is longer, before treatment initiation , or has ongoing clinically significant AEs from previous treatment with investigational agent
10. Cannot discontinue treatment with drugs that delay gastric emptying (GLP-1 and/or GIP agonists in Cycles 1 & 2.
11. Known hypersensitivity to cedazuridine or azacitidine or any excipients.
2. Poor medical risk due to any uncontrolled systemic diseases or active uncontrolled bacterial, viral, or fungal infections.
3. Known HIV infection.
4. Known positive for Hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months of screening
5. Life-threatening illness, uncontrolled medical condition or organ system dysfunction, or other reasons that, could compromise the participant's safety, interfere with the absorption or metabolism of ASTX030, or the integrity of study outcomes.
6.History of other malignancies, except certain adequately treated and/or controlled cancers, or early-stage cases not requiring therapy.
7. Extramedullary disease in MDS/MPN, including palpable hepatomegaly or splenomegaly
8. Prior treatment with > 1 cycle of decitabine or azacitidine
9. Treated with any investigational therapy within 2 weeks, or 5 half-lives, whichever is longer, before treatment initiation , or has ongoing clinically significant AEs from previous treatment with investigational agent
10. Cannot discontinue treatment with drugs that delay gastric emptying (GLP-1 and/or GIP agonists in Cycles 1 & 2.
11. Known hypersensitivity to cedazuridine or azacitidine or any excipients.
2. Poor medical risk due to any uncontrolled systemic diseases or active uncontrolled bacterial, viral, or fungal infections.
3. Known HIV infection.
DESCRIPCIÓN
Establish azacitidine AUC equivalence (90% CI 0.8, 1.25) between the final selected dose of ASTX030 from Phase 2 using FDC and SC azacitidine at 75 mg/m2/day across BSA ranges
PALABRAS CLAVE
acute myeloid leukemia, aml, chronic leukemia, chronic myeloid leukemia, chronic myelomonocytic leukemia (cmml), leucemia linfocítica crónica (llc / cll), leukemia, mds, myelodysplastic syndrome
