Multicenter Study of Combined Chemotherapy and Transplantation for Adult ALL

NCT ID: NCT07059156

Last Updated: 2025-07-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-01
• Study Completion Date: 2027-07-31

Brief Summary

This study aims to evaluate an integrated treatment protocol for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL), combining induction chemotherapy, consolidation therapy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) to improve treatment efficacy and survival rates. The single-arm, open-label, multicenter study will enroll 50 newly diagnosed patients aged 18-60 years. The induction phase employs the VICP+VEN regimen (vindesine, idarubicin, cyclophosphamide, prednisone combined with venetoclax), followed by consolidation therapy with either Hyper-CVAD or CAM protocols, with eligible patients proceeding to allo-HSCT. Primary endpoints include disease-free survival (DFS) and complete remission (CR) rates, while secondary endpoints encompass relapse rate, overall survival (OS), and safety. Patients will be followed for 2 years with regular monitoring of minimal residual disease (MRD) and adverse events. The protocol is designed to reduce relapse risk through intensive therapy and transplantation, offering a potential cure for high-risk patients.The goal is to complete the entire treatment within 4 months after diagnosis.

Detailed Description

1. Intervention Measures 1.1 Induction Therapy Regimen

VICP+VEN regimen:

• Vindesine: 3 mg/m²/day (max 4 mg), administered on days 1, 8, 15, 22.
• Idarubicin (IDA): 8 mg/m², days 1, 8, 15, 22.
• Cyclophosphamide (CTX): 500 mg/m², days 7, 21.
• Prednisone: 1 mg/kg/day, days 1-14; 0.5 mg/kg/day, days 15-28
• Venetoclax (VEN) 8-day ramp-up: Day 1: 100 mg, Day 2: 200 mg, Days 3-8: 400 mg/day 1.2 Pre-Treatment Regimen

Indications for pre-treatment:

• WBC ≥30×10⁹/L, or significant hepatosplenomegaly/lymphadenopathy.
• Laboratory signs of tumor lysis syndrome (e.g., electrolyte abnormalities).

Pre-treatment protocol:

• Glucocorticoids (e.g., prednisone or dexamethasone): Prednisone 1 mg/kg/day (PO/IV) for 3-5 days.
• Optional addition of CTX: 200 mg/m²/day IV for 3-5 days. 1.3 Post-CR Treatment

Principles:

1. MRD-positive or rising: Administer blinatumomab (CD19/CD3 bispecific antibody) for residual disease clearance, followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT).

2. MRD-negative/unknown: Continue multi-agent chemotherapy ± blinatumomab consolidation. Allo-HSCT for patients with high-risk clinical/genetic features.

1.4 Post-CR Consolidation Regimens

① Hyper-CVAD-B (Methotrexate/Cytarabine-based):

• Methotrexate (MTX): 1 g/m² IV over 24h (Day 1) with urine alkalinization (pH >7.0) and leucovorin rescue.
• Cytarabine (Ara-C): 1 g/m² IV q12h (Days 2-3; total 4 doses).
• Dexamethasone: 40 mg/day (PO/IV, Days 1-4).
• Cycle interval: 21-28 days (alternating with other regimens).

• CAM Regimen:
• CTX: 750 mg/m² IV (split over 2 days).
• Ara-C: 75 mg/m²/dose (8 days; 1-2 doses/day IV; if once daily, administer 5 days/week × 2 weeks).
• 6-MP: 50-75 mg/m²/day fasting (7-14 days PO). 1.5 Transplant-Eligible Subsequent Therapy
• Allo-HSCT for eligible patients after induction.
• Conditioning regimen: TBI-VP16-CY.
• Donor priority: HLA-matched sibling donor (MSD), Matched unrelated donor (MUD), Haploidentical donor (Haplo). (Consider age/donor health status).

1.6 Allo-HSCT Protocol 1.6.1 Conditioning Regimen (TBI-VP16-Cy/ATG):

• TBI: 5 Gy (Days -7 to -6).
• VP16: 10 mg/kg/day (Days -5 to -4).
• CTX: 30 mg/kg/day (Days -3 to -2).
• ATG: 7.5 mg/kg/day (Days -5 to -2). 1.6.2 GVHD Prophylaxis:
• Basiliximab (anti-CD25 mAb): 50 mg (Days +1, +4).
• Standard regimen: Cyclosporine (CsA): IV: 2 mg/kg/day (start Day -9; target level 150-250 μg/L). PO: 3-5 mg/kg/day BID (switch delayed until Day +10 if no aGVHD); Mycophenolate mofetil (MMF) + short-course methotrexate.

1.7 Non-Transplant Maintenance Therapy

Options:

• Hyper-CVAD-B (Methotrexate/Cytarabine-based):

• Methotrexate (MTX): 1 g/m² IV over 24h (Day 1) with urine alkalinization (pH >7.0) and leucovorin rescue.

• Cytarabine (Ara-C): 1 g/m² IV q12h (Days 2-3; total 4 doses).

• Dexamethasone: 40 mg/day (PO/IV, Days 1-4).
• Cycle interval: 21-28 days (alternating with other regimens).

• CAM Regimen:
• CTX: 750 mg/m² IV (split over 2 days).
• Ara-C: 75 mg/m²/dose (8 days; 1-2 doses/day IV; if once daily, administer 5 days/week × 2 weeks).
• 6-MP: 50-75 mg/m²/day fasting (7-14 days PO).

• Maintenance (6-MP/MTX alternating with V-Dex): 6-MP: 75 mg/m²/day at bedtime (Days 1-21); MTX: 20 mg/m² IM weekly × 3 weeks.*Adjust doses to maintain WBC ~3×10⁹/L, ANC 1.0-1.5×10⁹/L.*

Conditions

Acute Lymphoblastic Leukemia, Adult

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Multicenter Study of Combined Chemotherapy and Transplantation for Adult ALL

Group Type: EXPERIMENTAL

Induction Therapy Regimen

Intervention Type: DRUG

VICP+VEN regimen:

• Vindesine: 3 mg/m²/day (max 4 mg), administered on days 1, 8, 15, 22.
• Idarubicin (IDA): 8 mg/m², days 1, 8, 15, 22.
• Cyclophosphamide (CTX): 500 mg/m², days 7, 21.
• Prednisone: 1 mg/kg/day, days 1-14; 0.5 mg/kg/day, days 15-28
• Venetoclax (VEN) 8-day ramp-up: Day 1: 100 mg, Day 2: 200 mg, Days 3-8: 400 mg/day

Pre-Treatment Regimen

Intervention Type: DRUG

Indications for pre-treatment:

• WBC ≥30×10⁹/L, or significant hepatosplenomegaly/lymphadenopathy.
• Laboratory signs of tumor lysis syndrome (e.g., electrolyte abnormalities).

Pre-treatment protocol:

• Glucocorticoids (e.g., prednisone or dexamethasone): Prednisone 1 mg/kg/day (PO/IV) for 3-5 days.
• Optional addition of CTX: 200 mg/m²/day IV for 3-5 days.

Post-CR Treatment

Intervention Type: OTHER

Principles:

1. MRD-positive or rising: Administer blinatumomab (CD19/CD3 bispecific antibody) for residual disease clearance, followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT).

2. MRD-negative/unknown: Continue multi-agent chemotherapy ± blinatumomab consolidation. Allo-HSCT for patients with high-risk clinical/genetic features.

Post-CR Consolidation Regimens

Intervention Type: DRUG

① Hyper-CVAD-B (Methotrexate/Cytarabine-based):

• Methotrexate (MTX): 1 g/m² IV over 24h (Day 1) with urine alkalinization (pH >7.0) and leucovorin rescue.
• Cytarabine (Ara-C): 1 g/m² IV q12h (Days 2-3; total 4 doses).
• Dexamethasone: 40 mg/day (PO/IV, Days 1-4).
• Cycle interval: 21-28 days (alternating with other regimens).

② CAM Regimen:

• CTX: 750 mg/m² IV (split over 2 days).
• Ara-C: 75 mg/m²/dose (8 days; 1-2 doses/day IV; if once daily, administer 5 days/week × 2 weeks).
• 6-MP: 50-75 mg/m²/day fasting (7-14 days PO).

Transplant-Eligible Subsequent Therapy

Intervention Type: OTHER

• Allo-HSCT for eligible patients after induction.
• Conditioning regimen: TBI-VP16-CY.
• Donor priority: HLA-matched sibling donor (MSD), Matched unrelated donor (MUD), Haploidentical donor (Haplo).(Consider age/donor health status).

Allo-HSCT Protocol

Intervention Type: OTHER

1.6.1 Conditioning Regimen (TBI-VP16-Cy/ATG):

• TBI: 5 Gy (Days -7 to -6).
• VP16: 10 mg/kg/day (Days -5 to -4).
• CTX: 30 mg/kg/day (Days -3 to -2).
• ATG: 7.5 mg/kg/day (Days -5 to -2). 1.6.2 GVHD Prophylaxis:
• Basiliximab (anti-CD25 mAb): 50 mg (Days +1, +4).
• Standard regimen: Cyclosporine (CsA): IV: 2 mg/kg/day (start Day -9; target level 150-250 μg/L). PO: 3-5 mg/kg/day BID (switch delayed until Day +10 if no aGVHD); Mycophenolate mofetil (MMF) + short-course methotrexate.

Non-Transplant Maintenance Therapy Options

Intervention Type: OTHER

① Hyper-CVAD-B (Methotrexate/Cytarabine-based):

• Methotrexate (MTX): 1 g/m² IV over 24h (Day 1) with urine alkalinization (pH >7.0) and leucovorin rescue.
• Cytarabine (Ara-C): 1 g/m² IV q12h (Days 2-3; total 4 doses).
• Dexamethasone: 40 mg/day (PO/IV, Days 1-4).
• Cycle interval: 21-28 days (alternating with other regimens).

② CAM Regimen:

• CTX: 750 mg/m² IV (split over 2 days).
• Ara-C: 75 mg/m²/dose (8 days; 1-2 doses/day IV; if once daily, administer 5 days/week × 2 weeks).
• 6-MP: 50-75 mg/m²/day fasting (7-14 days PO).

• Maintenance (6-MP/MTX alternating with V-Dex): 6-MP: 75 mg/m²/day at bedtime (Days 1-21); MTX: 20 mg/m² IM weekly × 3 weeks.*Adjust doses to maintain WBC ~3×10⁹/L, ANC 1.0-1.5×10⁹/L.*

Interventions

Induction Therapy Regimen

VICP+VEN regimen:

• Vindesine: 3 mg/m²/day (max 4 mg), administered on days 1, 8, 15, 22.
• Idarubicin (IDA): 8 mg/m², days 1, 8, 15, 22.
• Cyclophosphamide (CTX): 500 mg/m², days 7, 21.
• Prednisone: 1 mg/kg/day, days 1-14; 0.5 mg/kg/day, days 15-28
• Venetoclax (VEN) 8-day ramp-up: Day 1: 100 mg, Day 2: 200 mg, Days 3-8: 400 mg/day

Intervention Type: DRUG

Pre-Treatment Regimen

Indications for pre-treatment:

• WBC ≥30×10⁹/L, or significant hepatosplenomegaly/lymphadenopathy.
• Laboratory signs of tumor lysis syndrome (e.g., electrolyte abnormalities).

Pre-treatment protocol:

• Glucocorticoids (e.g., prednisone or dexamethasone): Prednisone 1 mg/kg/day (PO/IV) for 3-5 days.
• Optional addition of CTX: 200 mg/m²/day IV for 3-5 days.

Intervention Type: DRUG

Post-CR Treatment

Principles:

1. MRD-positive or rising: Administer blinatumomab (CD19/CD3 bispecific antibody) for residual disease clearance, followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT).

2. MRD-negative/unknown: Continue multi-agent chemotherapy ± blinatumomab consolidation. Allo-HSCT for patients with high-risk clinical/genetic features.

Intervention Type: OTHER

Post-CR Consolidation Regimens

① Hyper-CVAD-B (Methotrexate/Cytarabine-based):

• Methotrexate (MTX): 1 g/m² IV over 24h (Day 1) with urine alkalinization (pH >7.0) and leucovorin rescue.
• Cytarabine (Ara-C): 1 g/m² IV q12h (Days 2-3; total 4 doses).
• Dexamethasone: 40 mg/day (PO/IV, Days 1-4).
• Cycle interval: 21-28 days (alternating with other regimens).

② CAM Regimen:

• CTX: 750 mg/m² IV (split over 2 days).
• Ara-C: 75 mg/m²/dose (8 days; 1-2 doses/day IV; if once daily, administer 5 days/week × 2 weeks).
• 6-MP: 50-75 mg/m²/day fasting (7-14 days PO).

Intervention Type: DRUG

Transplant-Eligible Subsequent Therapy

• Allo-HSCT for eligible patients after induction.
• Conditioning regimen: TBI-VP16-CY.
• Donor priority: HLA-matched sibling donor (MSD), Matched unrelated donor (MUD), Haploidentical donor (Haplo).(Consider age/donor health status).

Intervention Type: OTHER

Allo-HSCT Protocol

1.6.1 Conditioning Regimen (TBI-VP16-Cy/ATG):

• TBI: 5 Gy (Days -7 to -6).
• VP16: 10 mg/kg/day (Days -5 to -4).
• CTX: 30 mg/kg/day (Days -3 to -2).
• ATG: 7.5 mg/kg/day (Days -5 to -2). 1.6.2 GVHD Prophylaxis:
• Basiliximab (anti-CD25 mAb): 50 mg (Days +1, +4).
• Standard regimen: Cyclosporine (CsA): IV: 2 mg/kg/day (start Day -9; target level 150-250 μg/L). PO: 3-5 mg/kg/day BID (switch delayed until Day +10 if no aGVHD); Mycophenolate mofetil (MMF) + short-course methotrexate.

Intervention Type: OTHER

Non-Transplant Maintenance Therapy Options

① Hyper-CVAD-B (Methotrexate/Cytarabine-based):

• Methotrexate (MTX): 1 g/m² IV over 24h (Day 1) with urine alkalinization (pH >7.0) and leucovorin rescue.
• Cytarabine (Ara-C): 1 g/m² IV q12h (Days 2-3; total 4 doses).
• Dexamethasone: 40 mg/day (PO/IV, Days 1-4).
• Cycle interval: 21-28 days (alternating with other regimens).

② CAM Regimen:

• CTX: 750 mg/m² IV (split over 2 days).
• Ara-C: 75 mg/m²/dose (8 days; 1-2 doses/day IV; if once daily, administer 5 days/week × 2 weeks).
• 6-MP: 50-75 mg/m²/day fasting (7-14 days PO).

• Maintenance (6-MP/MTX alternating with V-Dex): 6-MP: 75 mg/m²/day at bedtime (Days 1-21); MTX: 20 mg/m² IM weekly × 3 weeks.*Adjust doses to maintain WBC ~3×10⁹/L, ANC 1.0-1.5×10⁹/L.*

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Age: 18 to 60 years；

2. Diagnosis must comply with the Chinese Guidelines for Diagnosis and Treatment of Adult Acute Lymphoblastic Leukemia (2024 Edition), requiring MICM (Morphology, Immunology, Cytogenetics, and Molecular genetics) integration and WHO 2022 (5th edition) classification standards. The minimal diagnostic workup must include morphological assessment and immunophenotyping to differentiate ALL from acute myeloid leukemia (AML). All patients shall undergo bone marrow aspiration plus biopsy at initial diagnosis. A definitive ALL diagnosis requires ≥20% blasts/immature lymphocytes in bone marrow (Note: Patients with <20% blasts due to fever or glucocorticoid pretreatment require comprehensive evaluation incorporating medical history and ancillary tests for differential diagnosis)；

3. ECOG Performance Status: 0-2

Exclusion Criteria

1. Intracranial hemorrhage

2. Pregnancy

3. Psychiatric disorders or other conditions compromising protocol compliance

4. Severe cardiac arrhythmia with ECG abnormalities (QTc >500 ms)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanxi Bethune Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Shanxi Bethune Hospital

Taiyuan, Shanxi, China

Site Status: RECRUITING

Countries

China

Central Contacts

Tao Wang, Dr.

Role: CONTACT

wangtao99699@163.com

13835175119

Facility Contacts

Tao Wang, Dr.

Role: primary

wangtao99699@163.com

13835175119

Other Identifiers

ShanxiBethuneH1

Identifier Type: -

Identifier Source: org_study_id