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

A Phase I/II, Prospective, Single-Arm, Single-Center Clinical Trial of CD38 Monoclonal Antibody Combined With a Pediatric-Inspired Chemotherapy Regimen for Induction Therapy in Adults With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia

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.

Study Overview

• Status: Withdrawn
• Conditions: T-ALL
• Intervention / Treatment: Drug: Pediatric-Inspired Chemotherapy Regimen

Detailed Description

This study is a prospective, single-arm, single-center phase I/II clinical trial. Eligible patients are adults newly diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) according to the WHO (2022) or ICC classification criteria and deemed suitable for standard chemotherapy regimens.Study Design:Phase I (Dose-Escalation Stage):Utilizes a "3+3" dose-escalation design to evaluate the safety, tolerability, and preliminary efficacy of CM313 in combination with a pediatric-inspired chemotherapy regimen for T-ALL induction therapy. Determine the recommended phase II dose (RP2D) for subsequent evaluation.Phase II (Expansion Stage):Plans to enroll 20 T-ALL patients treated with the VDCLP regimen (vincristine, daunorubicin, cyclophosphamide, L-asparaginase, and prednisone) combined with CM313 at the RP2D during induction therapy.Subsequent treatment phases include:Consolidation therapy、Early Intensification 1st、Delayed Intensification 1st、Early Intensification 2nd、Delayed Intensification 2nd and Maintenance therapy.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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:

  1. Hepatitis B surface antigen (HBsAg)-positive;
  2. Hepatitis B core antibody (HBcAb)-positive with detectable HBV DNA;
  3. 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:

  1. History of uncontrolled or symptomatic angina;
  2. Myocardial infarction within 6 months prior to study enrollment.
  3. History of arrhythmias requiring pharmacologic treatment or clinically significant arrhythmia;
  4. Uncontrolled or symptomatic congestive heart failure (CHF) > New York Heart Association (NYHA) Class II;
• Severe uncontrolled active infection.
• Psychiatric disorders that may compromise the patient's ability to complete treatment or provide informed consent.
• Any other condition deemed by the investigator to render the patient unsuitable for study participation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CM313 Level -1; 300mg D5,12；600mg D19,26	Drug: Pediatric-Inspired Chemotherapy Regimen; 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.
Experimental: CM313 Level 0; 600mg D5,12；1200mg D19,26	Drug: Pediatric-Inspired Chemotherapy Regimen; 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.
Experimental: CM313 Level 1; 1200 mg on Days 5, 12, 19, 26	Drug: Pediatric-Inspired Chemotherapy Regimen; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
The ratio of Complete remission (CR)/CR with partial hematologic recovery (CRh)/CR with incomplete hematologic recovery (CRi)	The ratio of patients achieved CR/CRh/CRi after therapy.	Six weeks after therapy
Rate of conversion from MRD+to MRD- by Next-generation sequencing (NGS) after induction therapy	Next-generation sequencing (NGS) is a high-throughput sequencing methodology and is a process by which small fragments of DNA are sequenced in parallel multiple times	30-days after induction therapy
overall survival	The interval from the date of enrollment to the date of death or the date of last follow-up, whichever occurred first	up to 2 years after the date of the last enrolled participants
Relapse free survival	This outcome analyzes patients achieved CR after therapy.	up to 2 years after the date of the last enrolled participants
Event-free survival (EFS)	This outcome analyzes patients who received the therapy.	up to 2 years after the date of the last enrolled participants
Cumulative incidence of relapse (CIR)	Cumulative incidence of relapse within 2 years post-treatment	up to 2 years after therapy
30-day mortality	Percentage of patients who died within 30 days from enrollment	within 30 days from the start of the trial
60-day mortality	Percentage of patients who died within 60 days from enrollment	within 60 days from the start of the trial

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2025
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: March 17, 2025
• First Submitted That Met QC Criteria: May 10, 2026
• First Posted (Actual): May 14, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 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; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hemic and Lymphatic Diseases; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: IIT2025027

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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