Clinical Trial of CD38 Monoclonal Antibody Combined With Chemotherapy for T-Cell Acute Lymphoblastic Leukemia

NCT07585734 | Withdrawn Phase 1

• 1 other identifier: IIT2025027
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Acute Lymphoblastic Leukemia (ALL) is a group of common hematological malignancies characterized by high aggressiveness and heterogeneity. Over the past 50 years, outcomes for pediatric ALL have significantly improved, with approximately 90% of children achieving long-term survival. In adults, ALL accounts for 20%-30% of acute leukemias, and nearly two-thirds of adult ALL cases are Philadelphia chromosome-negative (Ph-negative). Based on immunophenotype, Ph-negative ALL can be further classified into B-cell ALL (B-ALL) and T-cell ALL (T-ALL). T-ALL constitutes 15%-25% of Ph-negative ALL cases and is associated with poorer clinical prognosis compared to B-ALL, including lower induction remission rates and a higher risk of relapse, even among patients who achieve complete remission (CR). Over the past two decades, only nelarabine has been FDA-approved for relapsed/refractory T-ALL, but this drug is not available in China. Given the current therapeutic limitations, novel strategies to improve T-ALL outcomes are urgently needed. CD38, a cell surface antigen highly and stably expressed on T-ALL cells with minimal influence from prior chemotherapy, has emerged as a promising therapeutic target. Preliminary clinical data for daratumumab, a CD38-targeted monoclonal antibody, demonstrate improved objective response rates (ORR) in pediatric and young adult patients compared to historical controls, along with favorable safety and tolerability. CM313 injection (referred to as "CM313"), developed by Keymed Biosciences (Chengdu) Co., Ltd., is a humanized monoclonal antibody with proprietary intellectual property. Preclinical studies confirm that CM313 specifically binds to CD38 on the surface of hematologic tumor cells, including myeloma, lymphoma, and ALL. It exerts antitumor effects via multiple mechanisms: antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP), and Fc crosslinking-induced apoptosis. Additionally, CM313 inhibits CD38 ectoenzyme activity. In vitro and in vivo pharmacodynamic studies indicate comparable antitumor efficacy between CM313 and daratumumab. This study aims to evaluate the safety and efficacy of CM313 combined with pediatric-inspired chemotherapy regimens for induction therapy in adults with newly diagnosed T-ALL, providing a foundation for extending CD38 monoclonal antibody applications to T-ALL consolidation therapy.

Conditions

T-ALL

Outcome Measures

Primary Outcomes (2)

• To determine the maximum tolerated dose (MTD) of CM313 in combination with chemotherapy.

  The CM313 combination chemotherapy regimen is divided into three dose levels: dose level -1, dose level 0, and dose level +1.

  6 weeks after induction therapy

• MRD-negative complete remission (CR) rate by flow cytometry following induction therapy.

  Among those who have achieved CR after induction therapy, proportion of patients who is MRD-negative

  Up to approximately eight weeks

Secondary Outcomes (8)

• The ratio of Complete remission (CR)/CR with partial hematologic recovery (CRh)/CR with incomplete hematologic recovery (CRi)

  Six weeks after therapy

• Rate of conversion from MRD+to MRD- by Next-generation sequencing (NGS) after induction therapy

  30-days after induction therapy

• overall survival

  up to 2 years after the date of the last enrolled participants

• Relapse free survival

  up to 2 years after the date of the last enrolled participants

• Event-free survival (EFS)

  up to 2 years after the date of the last enrolled participants

Study Arms (3)

CM313 Level -1

EXPERIMENTAL

300mg D5,12；600mg D19,26

Drug: Pediatric-Inspired Chemotherapy Regimen

CM313 Level 0

EXPERIMENTAL

600mg D5,12；1200mg D19,26

Drug: Pediatric-Inspired Chemotherapy Regimen

CM313 Level 1

EXPERIMENTAL

1200 mg on Days 5, 12, 19, 26

Drug: Pediatric-Inspired Chemotherapy Regimen

Interventions

Pediatric-Inspired Chemotherapy Regimen DRUG

Induction therapy regimen VDCLP(vincristine, daunorubicin, cyclophosphamide, L-asparaginase, and prednisone) combined with CM313 ；Subsequent treatment phases include:Consolidation therapy、Early Intensification 1st、Delayed Intensification 1st、Early Intensification 2nd、Delayed Intensification 2nd and Maintenance therapy.

CM313 Level -1; CM313 Level 0; CM313 Level 1

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of T-cell acute lymphoblastic leukemia (T-ALL) according to the World Health Organization (WHO) 2022 classification or International Consensus Classification (ICC) criteria.
• Age ≥14 years, regardless of gender.
• CD38-positive expression on leukemic cells, confirmed by multicolor flow cytometry.
• Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-2.
• Laboratory parameters (assessed within 7 days prior to treatment):
• Total bilirubin ≤1.5 × upper limit of normal (ULN) for the corresponding age group.
• AST and ALT ≤2.5 × ULN for the corresponding age group.
• Serum creatinine \<2 × ULN for the corresponding age group.
• Cardiac enzymes \<2 × ULN for the corresponding age group.
• Left ventricular ejection fraction (LVEF) \>50%, measured by echocardiography (ECHO).
• Informed Consent Requirements:
• A written informed consent form must be signed prior to any study-specific procedures. The consent may be provided by the patient themselves, their legal guardian, or immediate family member. If obtaining consent directly from the patient is deemed clinically inappropriate or detrimental to the patient's treatment, consent must be obtained from the legal guardian or immediate family member.

You may not qualify if:

• Active central nervous system (CNS) leukemia or clinical manifestations of isolated extramedullary involvement of ALL.
• Relapsed/refractory patients (however, prior cytoreductive therapies such as hydroxyurea, corticosteroids, cyclophosphamide, or cytarabine are permitted).
• Chronic obstructive pulmonary disease (COPD) with forced expiratory volume in 1 second (FEV1) \<60% of predicted value, confirmed by pulmonary function testing.
• Moderate to severe persistent asthma within the past 2 years, or uncontrolled asthma of any type at screening.
• Positive serology for human immunodeficiency virus (HIV).
• Positive syphilis serology.
• Suspected or confirmed active tuberculosis (TB) infection.
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, defined as:
• Hepatitis B surface antigen (HBsAg)-positive;
• Hepatitis B core antibody (HBcAb)-positive with detectable HBV DNA;
• Anti-HCV antibody-positive with detectable HCV RNA.
• Concurrent malignancies of other organ systems requiring active therapy.
• Active cardiac disease, defined as any of the following:
• History of uncontrolled or symptomatic angina;
• Myocardial infarction within 6 months prior to study enrollment.

Sponsors & Collaborators

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

MeSH Terms

Conditions

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2025
• First Posted: May 14, 2026
• Study Start: April 30, 2025
• Primary Completion: April 30, 2026
• Study Completion (Estimated): April 30, 2027
• Last Updated: May 14, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share