Immunotargeted Therapy Plus Low-Dose Chemotherapy in Newly Diagnosed Adult Ph+ B-ALL

NCT07840976 | Not Yet Recruiting Phase 2

• 2 other identifiers: IIT2026061IIT2026061-EC-1
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, open-label, single-arm, umbrella phase 2 clinical trial enrolling 22 adult patients with newly diagnosed Philadelphia chromosome-positive (Ph+) B-cell acute lymphoblastic leukemia (ALL). As an umbrella trial, all patients share the same target disease (newly diagnosed Ph+ B-ALL) and receive a uniform induction backbone consisting of multi-targeted immunotherapy, targeted therapy, and reduced-intensity chemotherapy. After induction, patients are stratified and assigned to two distinct consolidation pathways based on clinical condition, performance status, resource availability, and patient preference: Pathway A: Consolidation with CD19-directed CAR-T cell therapy to achieve deep molecular remission; Pathway B: Consolidation with sequential immunochemotherapy to maximize minimal residual disease (MRD) clearance. A backup chemotherapy backbone is provided for patients ineligible for antibody therapy. All patients, regardless of consolidation pathway, proceed to a unified long-term maintenance regimen. The primary endpoint is the complete molecular remission (CMR) rate after one cycle of induction therapy. MRD is monitored longitudinally by flow cytometry, quantitative PCR, and immune repertoire sequencing. Safety is evaluated per NCI CTCAE version 5.0.

Conditions

Ph+ Acute Lymphoblastic Leukemia (Ph+ALL)

Outcome Measures

Primary Outcomes (1)

• Complete Molecular Remission (CMR) Rate After 1 Cycle of Induction Therapy

  The proportion of patients achieving complete molecular remission (CMR), defined as undetectable BCR::ABL1 transcript by quantitative PCR (BCR::ABL1/ABL1 ratio \< 0.001%), after 1 cycle of induction therapy.

  At the end of Cycle 1 (each cycle is 28 days, approximately 4 weeks from enrollment)

Secondary Outcomes (6)

• 3-Month Complete Remission (CR)

  3 months after study enrollment

• 3-Month MRD Negativity Rates

  3 months after study enrollment

• 2-Year Overall Survival (OS)

  2 years after the last patient enrollment

• 2-Year Disease-Free Survival (DFS)

  2 years after the last patient enrollment

• 2-Year Event-Free Survival (EFS)

  2 years after the last patient enrollment

Study Arms (1)

Immunotargeted Therapy + Low-Dose Chemotherapy Arm

EXPERIMENTAL

All patients receive a uniform induction therapy backbone combining targeted therapy, immunotherapy, and reduced-intensity chemotherapy. After induction, patients are stratified into two consolidation pathways based on clinical status: 1) CD19 CAR-T cell therapy; 2) sequential immunochemotherapy. All patients proceed to a unified long-term maintenance regimen.

Drug: olverembatinib; Drug: Venetoclax; Drug: Inotuzumab Ozogamicin (IO); Drug: Blinatumomab; Biological: CD19-directed chimeric antigen receptor (CAR-T) T cells

Interventions

olverembatinib DRUG

Third-generation tyrosine kinase inhibitor (TKI) targeting BCR::ABL1, administered orally daily as part of induction, consolidation, and maintenance therapy.

Immunotargeted Therapy + Low-Dose Chemotherapy Arm

Venetoclax DRUG

BCL-2 inhibitor administered orally daily during induction and consolidation cycles to enhance leukemic cell apoptosis.

Immunotargeted Therapy + Low-Dose Chemotherapy Arm

Inotuzumab Ozogamicin (IO) DRUG

Anti-CD22 antibody-drug conjugate (ADC) administered intravenously during induction and consolidation therapy.

Immunotargeted Therapy + Low-Dose Chemotherapy Arm

Blinatumomab DRUG

CD19/CD3 bispecific T-cell engager (BiTE) administered as continuous intravenous infusion during consolidation therapy.

Immunotargeted Therapy + Low-Dose Chemotherapy Arm

CD19-directed chimeric antigen receptor (CAR-T) T cells BIOLOGICAL

Autologous CD19 CAR-T cell therapy administered as a single intravenous infusion as optional consolidation therapy for eligible patients.

Immunotargeted Therapy + Low-Dose Chemotherapy Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Newly diagnosed, previously untreated Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph+ B-ALL) confirmed by cytogenetics and/or molecular testing
• Leukemic blasts expressing CD22
• Adequate organ function (renal, hepatic, cardiac)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Life expectancy ≥ 3 months
• Written informed consent obtained prior to any study-related procedures

You may not qualify if:

• Prior systemic anti-leukemic therapy, including chemotherapy, targeted therapy, or immunotherapy
• History of chronic myeloid leukemia (CML) or other hematologic malignancies
• Central nervous system (CNS) leukemia or extramedullary disease at diagnosis
• Uncontrolled active infection or severe comorbidities
• HIV positivity or known hepatitis B/C infection with active viral replication
• Pregnant or breastfeeding
• Inability to comply with study procedures or follow-up requirements

Sponsors & Collaborators

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

Study Sites (1)

Chinese Academy of Medical Sciences Hospital of Hematology (Chinese Academy of Medical Sciences Institute of Hematology)

Tianjin, Tianjin Municipality, 301600, China

Location

MeSH Terms

Interventions

olverembatinib; venetoclax; Inotuzumab Ozogamicin; blinatumomab

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Ying Wang, MD, PhD

CONTACT

+86 22-23608095; wangying1@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an umbrella trial with a sequential treatment design. All patients receive a uniform induction therapy backbone, then are stratified into two consolidation pathways based on clinical status and patient preference: 1) CD19 CAR-T cell therapy; 2) sequential immunochemotherapy. All patients proceed to the same maintenance phase.

Study Record Dates

• First Submitted: June 8, 2026
• First Posted: September 25, 2026
• Study Start (Estimated): October 12, 2026
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 31, 2030
• Last Updated: September 25, 2026

Record last verified: 2026-06

Locations

CN (1)