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.
調査の概要
状態
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前：Jing Lu Doctor
- 電話番号：86+0512-67781137
- メール：gloriajlu@163.com
研究場所
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Jiangsu
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Suzhou、Jiangsu、中国、215000
- The First Affiliated Hospital of Soochow University
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参加基準
適格基準
就学可能な年齢
- 子
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：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;
他の名前：
75mg/m² qd (D1-D7), subcutaneous injection; 28-day cycle, ≥2 cycles
他の名前：
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実験的：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;
他の名前：
75mg/m² qd (D1-D7), subcutaneous injection; 28-day cycle, ≥2 cycles
他の名前：
9μg/day (D8-D14), 28μg/day (D15-D21), continuous intravenous infusion
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Composite Complete Response (CRc) rate after 2 cycles of induction therapy
時間枠：From randomization to 2 cycles of induction before consolidation therapy（100 days）
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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)
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From randomization to 2 cycles of induction before consolidation therapy（100 days）
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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MRD negativity rate
時間枠：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
時間枠：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
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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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協力者と研究者
捜査官
- 主任研究者：Suning Chen、The First Affiliated Hospital of Soochow University Principal Investigator
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- MPAL-1
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
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