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.

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.

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.