Pediatric-Inspired Regimen Combined With Venetoclax and Immunotherapy for Adult Ph-Negative Acute Lymphoblastic Leukemia

A Prospective Cohort Study of a Pediatric-Inspired Chemotherapy Regimen Combined With Venetoclax and Immunotherapy for the Treatment of Adult Ph-Negative Acute Lymphoblastic Leukemia

This is a prospective, open-label, non-randomized cohort study evaluating the efficacy and safety of a pediatric-inspired chemotherapy regimen (IH-2014 based) combined with venetoclax and immunotherapy in adult patients with newly diagnosed Ph-negative Acute Lymphoblastic Leukemia (ALL). Patients aged ≥14years,≤60 years will be enrolled. Treatment includes induction, consolidation, early intensification, delayed intensification, and maintenance phases. The use and number of cycles of immunotherapy will be based on patient preference. The primary endpoint is Event-Free Survival (EFS) and MRD-negative CR rates after induction therapy(by flow cytometry and NGS). Secondary endpoints include Complete Remission (CR) rate, MRD-negative CR rates at 12 weeks (by flow cytometry and NGS), Overall Survival (OS), Relapse-Free Survival (RFS), and cumulative relapse rate.

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoblastic Leukemia, Adult
• Intervention / Treatment: Drug: VDCLP+V; Drug: Consolidation Therapy; Drug: Maintenance Therapy; Drug: Blinatumomab; Drug: Venetoclax; Procedure: CNS Prophylaxis; Procedure: CAR-T Cell Therapy; Procedure: Hematopoietic Stem Cell Transplantation (HSCT); Drug: 2VIP

Detailed Description

Adult Ph-negative ALL has inferior outcomes compared to childhood ALL. Pediatric-inspired regimens have improved survival in adolescent and young adult (AYA) patients. Venetoclax, a BCL-2 inhibitor, has shown preclinical sensitivity in Ph-negative ALL. Our center's previous IH-2022 regimen (a pediatric-inspired regimen combined with venetoclax protocol) showed promising efficacy and tolerability in adult patients.Immunotherapy is effective in ALL. This study aims to integrate immunotherapy into the pediatric-inspired backbone to optimize the regimen and improve survival outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 43
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hui Wei, Doctor; Phone Number: 13132507161; Email: weihui@ihcams.ac.cn

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300020
      • Recruiting
      • Blood Diseases Hospital
      • Contact: Hui Wei, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Newly diagnosed, previously untreated (except prednisone/hydroxyurea) Ph-negative ALL
• Age ≥14 years, ≤60 years
• ECOG performance status ≤2
• Adequate organ function (liver, kidney, cardiac)
• For patients of childbearing potential: use of effective contraception
• Willing and able to provide informed consent

Exclusion Criteria:

• Burkitt leukemia/lymphoma
• Acute leukemia of ambiguous lineage
• Pregnancy or lactation
• Severe uncontrolled active infection
• History of pancreatitis
• Uncontrolled diabetes (HbA1c >7.5%)
• Active gastrointestinal bleeding within 6 months
• Arterial/venous thrombosis within 6 months
• Known HIV positivity
• Severe psychiatric illness hindering compliance
• Any other condition deemed unsuitable by the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chemotherapy induction Arm; Induction Regimen 1 (VDCLP+V): Vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, and venetoclax. Patients with either CD22-negative or CD22-positive B-ALL will receive this regimen. Consolidation Therapy: Based on the pediatric-inspired IH-2022 protocol, including Vincristine , Daunorubicin , Cyclophosphamide, Pegaspargase , Prednisone, Dexamethasone, Cytarabine, 6-Mercaptopurine , and High-Dose Methotrexate. Immunotherapy: Blinatumomab - optional, 1 to 4 cycles, starting post-induction, alternating with chemotherapy cycles. CAR-T Cell Therapy- optional: the third cycle. Maintenance Therapy: Consists of a monthly MM regimen and a VP plus Venetoclax regimen every 3 months. CNS Prophylaxis Allogeneic or autologous Hematopoietic Stem Cell Transplantation is considered for high-risk patients or those with positive MRD after induction.	Drug: VDCLP+V; Vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, and venetoclax.; Drug: Consolidation Therapy; Includes vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, dexamethasone, cytarabine, 6-mercaptopurine, and high-dose methotrexate.; Drug: Maintenance Therapy; Monthly MM regimen (6-mercaptopurine and methotrexate) and every 3 months VP (vincristine and prednisone) plus venetoclax.; Drug: Blinatumomab; Optional; 1 to 4 cycles (28 days each) based on patient choice, starting post-induction, alternating with chemotherapy cycles.; Drug: Venetoclax; Oral targeted therapy administered during induction, consolidation, and maintenance phases as per protocol; Procedure: CNS Prophylaxis; Intrathecal injection (methotrexate, cytarabine, dexamethasone) for a total of at least 15 sessions. Prophylactic cranial irradiation (18 Gy) is an alternative for patients unable or unwilling to receive intrathecal injections.; Procedure: CAR-T Cell Therapy; Preconditioning regimen with fludarabine and cyclophosphamide (FC) administered after the third course (second consolidation) for patients receiving CAR-T.; Procedure: Hematopoietic Stem Cell Transplantation (HSCT); Allogeneic or autologous HSCT considered for high-risk patients or those with positive MRD after induction in CR1, provided a suitable donor is available.
Experimental: Immunotherapy induction Arm; Induction Regimen 2 (2VIP): Inotuzumab ozogamicin, venetoclax, vincristine, and prednisone. For patients with CD22-positive B-ALL (≥20% blasts), especially those aged >55 years, the 2VIP regimen is recommended. Consolidation Therapy: Based on the pediatric-inspired IH-2022 protocol, including Vincristine , Daunorubicin , Cyclophosphamide, Pegaspargase , Prednisone, Dexamethasone, Cytarabine, 6-Mercaptopurine , and High-Dose Methotrexate. Immunotherapy: Blinatumomab - optional, 1 to 4 cycles, starting post-induction, alternating with chemotherapy cycles. CAR-T Cell Therapy- optional: the third cycle. Maintenance Therapy: Consists of a monthly MM regimen and a VP plus Venetoclax regimen every 3 months. CNS Prophylaxis Allogeneic or autologous Hematopoietic Stem Cell Transplantation is considered for high-risk patients or those with positive MRD after induction.	Drug: Consolidation Therapy; Includes vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, dexamethasone, cytarabine, 6-mercaptopurine, and high-dose methotrexate.; Drug: Maintenance Therapy; Monthly MM regimen (6-mercaptopurine and methotrexate) and every 3 months VP (vincristine and prednisone) plus venetoclax.; Drug: Blinatumomab; Optional; 1 to 4 cycles (28 days each) based on patient choice, starting post-induction, alternating with chemotherapy cycles.; Drug: Venetoclax; Oral targeted therapy administered during induction, consolidation, and maintenance phases as per protocol; Procedure: CNS Prophylaxis; Intrathecal injection (methotrexate, cytarabine, dexamethasone) for a total of at least 15 sessions. Prophylactic cranial irradiation (18 Gy) is an alternative for patients unable or unwilling to receive intrathecal injections.; Procedure: CAR-T Cell Therapy; Preconditioning regimen with fludarabine and cyclophosphamide (FC) administered after the third course (second consolidation) for patients receiving CAR-T.; Procedure: Hematopoietic Stem Cell Transplantation (HSCT); Allogeneic or autologous HSCT considered for high-risk patients or those with positive MRD after induction in CR1, provided a suitable donor is available.; Drug: 2VIP; Inotuzumab ozogamicin, venetoclax, vincristine, and prednisone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Event-Free Survival	up to 5 years
MRD-negative CR rate by flow cytometry after induction regimen	up to 6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival (OS)	Up to 5 years
Complete Remission Rate	up to 1 year
MRD-negative CR rate by flow cytometry at 12 weeks	up to 12 weeks
MRD-negative CR rate by NGS at 12 weeks	up to 12 weeks
Relapse-Free Survival (RFS)	Up to 5 years
Cumulative Incidence of Relapse	Up to 5 years

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2030

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: March 24, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 10, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Transplantation; Health Care Facilities Workforce and Services; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Immunologic Techniques; Stem Cell Transplantation; Immunomodulation; Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; venetoclax; blinatumomab; Hematopoietic Stem Cell Transplantation; Maintenance; Immunotherapy, Adoptive
• Other Study ID Numbers: IIT2026003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No