Ignite Creation Date:
2025-12-24 @ 11:17 PM
Ignite Modification Date:
2026-01-01 @ 5:46 AM
Study NCT ID:
NCT07059156
Status:
RECRUITING
Last Update Posted:
2025-07-10
First Post:
2025-07-01
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Multicenter Study of Combined Chemotherapy and Transplantation for Adult ALL
Sponsor:
Shanxi Bethune Hospital
Organization:
Study Overview
Official Title:
Multicenter Study on Integrated Treatment Regimen of Induction-Consolidation Chemotherapy and Transplantation for Adult Acute Lymphoblastic Leukemia
Status:
RECRUITING
Status Verified Date:
2025-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.\*
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.\*
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: