Full-course Immunotherapy Combined With Chemotherapy in Newly Diagnosed B-cell Acute Lymphoblastic Leukemia (FLOW)
This is a single-arm, prospective, phase 2 clinical trial evaluating the improvement of survival outcomes of blinatumomab combined with chemotherapy as a full-course treatment regimen in patients with newly diagnosed Philadelphia chromosome-negative (Ph-negative) B-cell precursor acute lymphoblastic leukemia (B-ALL). The study adopts a "reduced-dose chemotherapy + full-course immunotherapy" strategy: induction therapy with reduced-dose chemotherapy combined with blinatumomab to improve remission rate and tolerability; consolidation therapy with alternating Hyper-CVAD (A/B) regimen，blinatumomab and sequential CD19-directed CAR-T therapy to deepen minimal residual disease (MRD) clearance; allogeneic hematopoietic stem cell transplantation (allo-HSCT) for some patients (e.g., KMT2A rearrangement, TP53 mutation, persistent MRD positivity, MRD recurrence); and no maintenance therapy.
The primary endpoint is 2-year relapse-free survival (RFS). Secondary endpoints include 2-year overall survival (OS), the proportion and time to achieve complete response (CRc), and the proportion and time to achieve minimal residual disease (MRD) negativity.
The trial plans to enroll 101 patients aged 15-65 years to demonstrate improved survival outcomes compared with historical controls .
연구 개요
상태
연구 유형
등록 (추정된)
단계
- 2 단계
연락처 및 위치
연구 연락처
- 이름: Jing Lu Doctor
- 전화번호: 86+0512-67781137
- 이메일: gloriajlu@163.com
연구 장소
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Jiangsu
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Suzhou, Jiangsu, 중국, 215000
- 모병
- The First Affiliated Hospital of Soochow University
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연락하다:
- Jing Lu
- 전화번호: 86+0512-67781137
- 이메일: gloriajlu@163.com
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-
참여기준
자격 기준
공부할 수 있는 나이
- 어린이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
Inclusion Criteria:
- Age ≥15 years and ≤65 years.
- Newly diagnosed Ph-negative B-cell precursor acute lymphoblastic leukemia (B-ALL) according to WHO diagnostic criteria, with CD19 expression ≥ 20%
- De novo patients with no prior induction therapy (excluding hydroxyurea and corticosteroid use for ≤ 5 days)
- ECOG performance status score 0-3.
- Liver function: Total bilirubin ≤ 3 times the upper limit of normal (ULN); alanine transaminase (ALT) ≤ 3×ULN; aspartate transaminase (AST) ≤ 3×ULN; (leukemic infiltration is excluded).
- Renal function: Creatinine clearance rate (CrCl) ≥ 30 mL/min
- Able to understand and voluntarily participate in the study, and provide written informed consent
Exclusion Criteria:
- Philadelphia chromosome-positive (Ph+, BCR-ABL1+) ALL
- T-cell acute lymphoblastic leukemia
- Mature B-cell leukemia/lymphoma, B-cell lymphoblastic lymphoma, extramedullary invasion
- Acute mixed phenotype acute leukemia (MPAL)
- Central nervous system (CNS) leukemia
- HIV infection
- Positive HBV-DNA or HCV-RNA
- New York Heart Association (NYHA) functional class ≥ II, or other conditions deemed unsuitable for enrollment by the investigator
- Pregnant or lactating patients
- Patients who refuse to enroll in the study
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: Experimental Arm:Blinatumomab + Chemotherapy
Patients receive reduced-dose chemotherapy combined with blinatumomab for induction, followed by alternating Hyper-CVAD(A/B) chemotherapy, blinatumomab and sequential CD19-directed CAR-T therapy for consolidation.
Patients (e.g., KMT2A rearrangement, TP53 mutation, persistent MRD positivity, MRD recurrence)receive allogeneic hematopoietic stem cell transplantation.
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Induction phase: 9 µg/day on days 8-14, 28 µg/day on days 15-21; If D22 BM not CR/CRi, continue Blinatumomab for next 2 weeks of 28 µg/day; Consolidation phase: 28 µg/day for 28 days.
Reduced-dose induction regimen: Idarubicin 8 mg/m², intravenous, day 1; Vindesine 3 mg/m² (max 4 mg), intravenous, day 1; Dexamethasone 9 mg/m²/day, intravenous, days 1-7. Combined with blinatumomab Alternating intensive consolidation chemotherapy: Hyper-CVAD-A: Cyclophosphamide ,Vincristine , Doxorubicin , Dexamethasone ; Hyper-CVAD-B: Methotrexate , Cytarabine . Alternated with CD19-CART and blinatumomab
Allogeneic hematopoietic stem cell transplantation, performed after consolidation therapy in patients with KMT2A rearrangement, TP53 mutation, persistent MRD positivity or MRD recurrence
CD19-CART is administered sequentially in the consolidation phase: First infusion : Following the first course of blinatumomab (28 µg/day, IV, days 1-28) before subsequent Hyper-CVAD chemotherapy. Second infusion : After completion of alternating Hyper-CVAD and blinatumomab consolidation cycles. |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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2-year relapse-free survival (RFS)
기간: From enrollment through 2 years post-last patient enrolled
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Defined as the time from enrollment to relapse, death from any cause, or last follow-up, whichever occurs first.
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From enrollment through 2 years post-last patient enrolled
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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2-year overall survival (OS)
기간: From enrollment through 2 years post-last patient enrolled
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Defined as the time from enrollment to death from any cause or last follow-up, whichever occurs first.
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From enrollment through 2 years post-last patient enrolled
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Composite Complete Remission (CR/CRi) Rate after Induction Therapy
기간: From randomization to 2 cycles of induction before consolidation therapy(100 days)
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Proportion of patients achieving complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) after induction phase.CRc is evaluated at: 1) Day 22 after initial induction therapy; 2) After re-induction with blinatumomab for 2 weeks (for patients not achieving CRc at Day 22)
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From randomization to 2 cycles of induction before consolidation therapy(100 days)
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Minimal Residual Disease (MRD) Negativity Rate
기간: From randomization to 2 cycles of induction before consolidation therapy(100 days)
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Proportion of patients achieving MRD negativity (detected by next-generation sequencing, NGS, sensitivity ≥10-⁵) at multiple time points: after first Hyper-CVAD-B chemotherapy, after second Hyper-CVAD-B chemotherapy, and after CD19-CART2 therapy.
MRD negativity is defined as <10-⁵ leukemic blasts in bone marrow.
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From randomization to 2 cycles of induction before consolidation therapy(100 days)
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공동 작업자 및 조사자
수사관
- 수석 연구원: Suning Chen, The First Affiliated Hospital of Soochow University
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- ALL-03
개별 참가자 데이터(IPD) 계획
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