A Phase 2 Study of Bcl-2 Inhibitor Combined With Azacitidine for Newly Diagnosed Mixed Phenotype Acute Leukemia
A Prospective, Open-Label, Single-Arm, Two-Cohort Phase 2 Clinical Study to Evaluate the Efficacy and Safety of Bcl-2 Inhibitor Combined With Azacitidine in the Treatment of Newly Diagnosed Mixed Phenotype Acute Leukemia
This is a prospective, open-label, single-arm, two-cohort Phase 2 clinical study designed to evaluate the efficacy and safety of Bcl-2 Inhibitor combined with azacitidine (with blinatumomab added in B/myeloid subtype) in patients with newly diagnosed mixed phenotype acute leukemia (MPAL). Eligible subjects are divided into two cohorts based on immunophenotype: Cohort A (T/Myeloid MPAL) receives Bcl-2 Inhibitor + azacitidine, and Cohort B (B/Myeloid MPAL) receives Bcl-2 Inhibitor + azacitidine + blinatumomab. The treatment cycle is 28 days, with the primary efficacy endpoint assessed after 2 cycles of induction therapy. Patients who achieve CRc will undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) following 2 to 3 cycles of consolidation therapy.The total enrollment period is 24 months, and all subjects will be followed up for at least 24 months from the first day of the first cycle (C1D1).
The primary objective is to evaluate the composite complete response (CRc) rate after 2 cycles of induction therapy , and the secondary objectives include evaluating measurable residual disease (MRD) negativity rate, bridge-to-allogeneic hematopoietic stem cell transplantation (allo-HSCT) rate in first complete response (CR1), overall survival(OS),Event-Free Survival(EFS),Relapse-Free Survival(RFS) and Safety.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Fase 2
Kontakter og lokationer
Studiekontakt
- Navn: Jing Lu Doctor
- Telefonnummer: 86+0512-67781137
- E-mail: gloriajlu@163.com
Studiesteder
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Jiangsu
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Suzhou, Jiangsu, Kina, 215000
- The First Affiliated Hospital of Soochow University
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
- Barn
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Beskrivelse
Inclusion Criteria:
- Aged 16 to 70 years old
- Newly diagnosed MPAL confirmed by the 2022 WHO/ICC classification criteria for hematopoietic and lymphoid neoplasms
- Previously untreated; use of glucocorticoids or hydroxyurea for ≤7 days to control tumor burden before enrollment is allowed, no other systemic anti-leukemia therapy
- ECOG performance status score 0-3
- No severe combined heart, brain, lung, liver or kidney disease, judged by the investigator to tolerate the study regimen
- Able to understand and voluntarily sign a written informed consent form
Exclusion Criteria:
- BCR::ABL-positive MPAL patients
- Presence of active, uncontrolled infection
- Known uncontrolled active central nervous system leukemia (CNSL)
- Life-threatening extramedullary disease requiring urgent radiotherapy or surgical debulking
- Severe cardiac insufficiency with left ventricular ejection fraction (LVEF) <40%
- Previous receipt of systemic anti-leukemia therapy
- Pregnant or lactating female subjects
- Judged by the investigator to be ineligible for the study for other reasons
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Cohort A: T/Myeloid MPAL
Sonrotoclax: 40mg qd (D1), 80mg qd (D2), 160mg qd (D3), 320mg qd (D4-D21), oral; Azacitidine: 75mg/m² qd (D1-D7), subcutaneous injection; 28-day cycle, ≥2 cycles. Patients who achieve CRc will undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) following 2 to 3 cycles of consolidation therapy. |
Sonrotoclax:40mg qd (D1), 80mg qd (D2), 160mg qd (D3), 320mg qd (D4-D21), oral;
Andre navne:
75mg/m² qd (D1-D7), subcutaneous injection; 28-day cycle, ≥2 cycles
Andre navne:
|
|
Eksperimentel: Cohort B: B/Myeloid MPAL
Sonrotoclax: 40mg qd (D1), 80mg qd (D2), 160mg qd (D3), 320mg qd (D4-D21), oral; Azacitidine: 75mg/m² qd (D1-D7), subcutaneous injection; Blinatumomab: 9μg/day (D8-D14), 28μg/day (D15-D21), continuous intravenous infusion; 28-day cycle, ≥2 cycles. Patients who achieve CRc will undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) following 2 to 3 cycles of consolidation therapy. |
Sonrotoclax:40mg qd (D1), 80mg qd (D2), 160mg qd (D3), 320mg qd (D4-D21), oral;
Andre navne:
75mg/m² qd (D1-D7), subcutaneous injection; 28-day cycle, ≥2 cycles
Andre navne:
9μg/day (D8-D14), 28μg/day (D15-D21), continuous intravenous infusion
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Composite Complete Response (CRc) rate after 2 cycles of induction therapy
Tidsramme: From randomization to 2 cycles of induction before consolidation therapy（100 days）
|
CRc = CR + CRi; CR: bone marrow blasts <5%, no extramedullary disease, no peripheral blasts, ANC ≥1.0×10⁹/L,
PLT ≥100×10⁹/L; CRi: bone marrow blasts <5%, no extramedullary disease, no peripheral blasts, incomplete hematologic recovery (ANC <1.0×10⁹/L or PLT <100×10⁹/L)
|
From randomization to 2 cycles of induction before consolidation therapy（100 days）
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
MRD negativity rate
Tidsramme: From randomization to 2 cycles of induction before consolidation therapy（100 days）
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Bone marrow MRD <0.01%
detected by MFC
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From randomization to 2 cycles of induction before consolidation therapy（100 days）
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NGS-MRD negativity rate
Tidsramme: From randomization to 2 cycles of induction before consolidation therapy（100 days）, and test Every 3 months during follow-up
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NGS-MRD can not detected by IgH/TCR NGS (NGS-based MRD will be incorporated as an exploratory complementary assay in patients with trackable clonotypic rearrangements at diagnosis)
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From randomization to 2 cycles of induction before consolidation therapy（100 days）, and test Every 3 months during follow-up
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CR1 bridge-to-allo-HSCT rate
Tidsramme: Up to 6 months after enrollment
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Proportion of subjects who achieve CR/CRi and successfully receive allo-HSCT within 2-3 cycles
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Up to 6 months after enrollment
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Overall Survival (OS)
Tidsramme: From the time from randomization to time for up to 2 years
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Time from C1D1 to death from any cause; data censored at last follow-up for surviving subjects
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From the time from randomization to time for up to 2 years
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Event-Free Survival (EFS)
Tidsramme: From the time from randomization to time for up to 2 years
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Time from C1D1 to first event (no CRc after 2 cycles, morphological/extramedullary relapse, disease progression, off-protocol anti-leukemia therapy, death from any cause); data censored at last follow-up for event-free subjects
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From the time from randomization to time for up to 2 years
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Relapse-Free Survival (RFS)
Tidsramme: From the time from randomization to time for up to 2 years
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Time from first CR/CRi to relapse or death from any cause; relapse defined as bone marrow blasts ≥5%, extramedullary disease, peripheral blasts, or molecular MRD ≥10-⁴ in previously MRD-negative patients;data censored at last follow-up for relapse-free subjects
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From the time from randomization to time for up to 2 years
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100-day Non-Relapse Mortality (100-day NRM)
Tidsramme: Up to 100 days after initial MPAL diagnosis
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Proportion of deaths from non-relapse causes within 100 days of diagnosis
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Up to 100 days after initial MPAL diagnosis
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Incidence of grade ≥3 adverse events (AEs)
Tidsramme: From treatment initiation to the end of Induction
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Type, frequency and severity of grade ≥3 AEs graded by CTCAE v5.0
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From treatment initiation to the end of Induction
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Samarbejdspartnere og efterforskere
Efterforskere
- Ledende efterforsker: Suning Chen, The First Affiliated Hospital of Soochow University Principal Investigator
Datoer for undersøgelser
Studer store datoer
Studiestart (Anslået)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- MPAL-1
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
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