Comparing the Efficacy of the LDA, LHAA, and DA Regimens in Young Adults With Low-Risk Acute Myeloid Leukemia Eligible for Intensive Chemotherapy
A Multicenter, Prospective, Randomized Controlled Clinical Study Comparing the Efficacy of the LDA, LHAA, and DA Regimens in Young Adults With Low-Risk Acute Myeloid Leukemia Eligible for Intensive Chemotherapy
Studieoversikt
Status
Forhold
Studietype
Registrering (Antatt)
Fase
- Fase 2
- Fase 3
Kontakter og plasseringer
Studiesteder
-
-
Zhejiang
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Hangzhou, Zhejiang, Kina, 310000
- The First Affiliated Hospital of Zhejiang University
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Beskrivelse
Inclusion Criteria:
- Newly diagnosed acute myeloid leukemia (AML) confirmed according to the World Health Organization (WHO) classification;
- Classified as intermediate- or adverse-risk AML based on the European LeukemiaNet (ELN) 2022 genetic risk stratification;
- Age 18-65 years;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
- Adequate hepatic and renal function: total bilirubin ≤2 mg/dL (35 μmol/L); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2× the upper limit of normal; serum creatinine ≤177 μmol/L;
- Normal cardiac function, defined as left ventricular ejection fraction (LVEF) >50%;
- Life expectancy ≥3 months;
- Signed written informed consent by the patient or their legally authorized representative prior to study enrollment.
Exclusion Criteria:
- Acute promyelocytic leukemia;
- Central nervous system involvement by leukemia;
- History of other malignancies within the past 5 years;
- Positive for human immunodeficiency virus (HIV);
- Presence of any other serious medical condition that may limit study participation, including advanced infections, uncontrolled diabetes mellitus, severe cardiac insufficiency, or angina;
- Ineligible for intensive chemotherapy due to poor general condition;
- Pregnant or breastfeeding women;
- Inability to understand or comply with the study protocol;
- Inability to take oral medication or presence of malabsorption syndrome;
- Prior treatment with B-cell lymphoma 2 (BCL-2) inhibitors or hypomethylating agents, or current participation in any other investigational drug study;
- Inability or unwillingness to provide written informed consent.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Arm A: Lisaftoclax+Daunorubicin+Cytarabine
Participants received induction chemotherapy with lisaftoclax, daunorubicin, and cytarabine. Patients achieving partial response (PR) with a reduction in bone marrow blasts >60% were allowed to receive one additional cycle of the same regimen. Patients who achieved complete response received consolidation therapy with lisaftoclax in combination with intermediate-dose cytarabine for 3 cycles. After completion of consolidation therapy, next-generation sequencing (NGS) was performed. Patients with minimal residual disease (MRD) negativity did not receive maintenance therapy, whereas patients with MRD positivity proceeded to maintenance therapy. Maintenance therapy consisted of lisaftoclax in combination with azacitidine, administered for up to 1 year or 10 cycles, whichever occurred first. |
Lisaftoclax (200 mg on D2, 400 mg on D3, and 600 mg qd on D4-8, orally) + daunorubicin (60 mg/m², iv, qd, D1-3) + cytarabine (100 mg/m², q12h, subcutaneous injection or iv infusion, D1-7).
Andre navn:
Lisaftoclax (600 mg, orally, D1-7) + intermediate-dose cytarabine (2 g/m², q12h, D1-3) for 3 cycles
Andre navn:
Lisaftoclax (400 mg, orally, D1-7) + azacitidine (50 mg/m², D1-7) for up to 1 year or 10 cycles, whichever occurred first.
Andre navn:
|
|
Eksperimentell: Arm B: Lisaftoclax+homoharringtonine+cytarabine+aclarubicin
Participants received induction chemotherapy with lisaftoclax, homoharringtonine, cytarabine, and aclarubicin. Patients achieving partial response (PR) with a reduction in bone marrow blasts >60% were allowed to receive one additional cycle of the same regimen. Patients who achieved complete response received consolidation therapy with lisaftoclax in combination with intermediate-dose cytarabine for 3 cycles. After completion of consolidation therapy, next-generation sequencing (NGS) was performed. Patients with minimal residual disease (MRD) negativity did not receive maintenance therapy, whereas patients with MRD positivity proceeded to maintenance therapy. Maintenance therapy consisted of lisaftoclax in combination with azacitidine, administered for up to 1 year or 10 cycles, whichever occurred first. |
Lisaftoclax (600 mg, orally, D1-7) + intermediate-dose cytarabine (2 g/m², q12h, D1-3) for 3 cycles
Andre navn:
Lisaftoclax (400 mg, orally, D1-7) + azacitidine (50 mg/m², D1-7) for up to 1 year or 10 cycles, whichever occurred first.
Andre navn:
Lisaftoclax (200 mg on D2, 400 mg on D3, and 600 mg qd on D4-8, orally) + homoharringtonine (2 mg/m², qd, intramuscular injection or iv infusion, D1-5) + cytarabine (100 mg/m², q12h, subcutaneous injection or iv infusion, D1-5) + aclarubicin (12 mg/m², maximum 20 mg, iv, D1-5).
Andre navn:
|
|
Aktiv komparator: Arm C: Daunorubicin+cytarabine
Participants received induction chemotherapy with daunorubicin and cytarabine. Patients achieving partial response (PR) with a reduction in bone marrow blasts >60% were allowed to receive one additional cycle of the same regimen. Patients who achieved complete response received consolidation therapy with lisaftoclax in combination with intermediate-dose cytarabine for 3 cycles. After completion of consolidation therapy, next-generation sequencing (NGS) was performed. Patients with minimal residual disease (MRD) negativity did not receive maintenance therapy, whereas patients with MRD positivity proceeded to maintenance therapy. Maintenance therapy consisted of lisaftoclax in combination with azacitidine, administered for up to 1 year or 10 cycles, whichever occurred first. |
Lisaftoclax (600 mg, orally, D1-7) + intermediate-dose cytarabine (2 g/m², q12h, D1-3) for 3 cycles
Andre navn:
Lisaftoclax (400 mg, orally, D1-7) + azacitidine (50 mg/m², D1-7) for up to 1 year or 10 cycles, whichever occurred first.
Andre navn:
Daunorubicin (60 mg/m², iv, qd, D1-3) + cytarabine (100 mg/m², q12h, subcutaneous injection or iv infusion, D1-7).
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
2-year event-free survival (EFS) rate
Tidsramme: from randomization up to 2 years after randomization
|
defined as the proportion of patients remaining free of treatment failure, hematologic relapse, MRD relapse, or death within 2 years after randomization.
|
from randomization up to 2 years after randomization
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Complete Response (CR) rate after 1/2 treatment cycles
Tidsramme: At the end of Cycle 1 or Cycle 2 induction chemotherapy (each cycle is 28 days)
|
defined as the proportion of patients achieving complete response (CR) after the first or second cycle of induction chemotherapy.
|
At the end of Cycle 1 or Cycle 2 induction chemotherapy (each cycle is 28 days)
|
|
Composite Complete Response (CRc) rate after 1/2 treatment cycles
Tidsramme: At the end of Cycle 1 or Cycle 2 induction chemotherapy (each cycle is 28 days)
|
defined as the proportion of patients achieving CRc after the first or second cycle of induction chemotherapy.
|
At the end of Cycle 1 or Cycle 2 induction chemotherapy (each cycle is 28 days)
|
|
Minimal residual disease (MRD) negativity rate after 1-2 cycles of induction chemotherapy
Tidsramme: At the end of Cycle 1 or Cycle 2 induction chemotherapy (each cycle is 28 days)
|
defined as the the proportion of patients with negative minimal residual disease (MRD) among patients who achieve complete remission after 1-2 cycles of induction chemotherapy
|
At the end of Cycle 1 or Cycle 2 induction chemotherapy (each cycle is 28 days)
|
|
2-year overall survival rate (OS)
Tidsramme: from randomization up to 2 years
|
defined as the proportion of patients who were still alive from the time of randomization for the last patient until 24 months later
|
from randomization up to 2 years
|
|
2-year relapse-free survival (RFS) rate
Tidsramme: from the date of complete remission (CR/CRi) up to 2 years after achieving response
|
defined as the proportion of patients who achieved complete response (CR) or complete remission with incomplete hematologic recovery (CRi) and remained alive without disease relapse within 2 years after achieving response.
|
from the date of complete remission (CR/CRi) up to 2 years after achieving response
|
|
Safety and Tolerability
Tidsramme: up to 24 months
|
defined as the number of participants with adverse events and serious adverse events as assessed by NCI CTCAE v5.0
|
up to 24 months
|
Samarbeidspartnere og etterforskere
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- CN-ZY-26-01
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