NCT07059156

Multicenter Study of Combined Chemotherapy and Transplantation for Adult ALL

Multicenter Study on Integrated Treatment Regimen of Induction-Consolidation Chemotherapy and Transplantation for Adult Acute Lymphoblastic Leukemia

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Shanxi Bethune Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
DRUG	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
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.
OTHER	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.
DRUG	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).
OTHER	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).
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.
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.\*

Timeline

• Start date: 2025-06-01
• Primary completion: 2027-06-01
• Completion: 2027-07-01
• First posted: 2025-07-10
• Last updated: 2025-07-10

Locations

1 site across 1 country: China