Daratumumab for T Cell ALL With MRD-positive After Standard Chemotherapy (T-ALL-2024)

A Prospective, Single-arm, Multicenter, Open-label , Phase 2 Study to Evaluate Efficacy and Safety of the Daratumumab in T Cell Acute Lymphoblastic Leukemia With Minimal Residual-Positive After Standard Chemotherapy

T-ALL accounts for about 15%-25% of Ph-negative ALL, and its clinical prognosis is worse than B-ALL. The successful application of immunotherapy has brought revolutionary progress to the treatment of ALL. But progress in the treatment of T-ALL has been relatively slow. Minimal residual disease (MRD) is a strong prognostic indicator for ALL patients. MRD-positive after induction therapy predicts a high risk of relapse. The National Comprehensive Cancer Network (NCCN) considers MRD-positive ALL patients to be at high risk. Research in the B-ALL field has demonstrated that immunotherapy has the potential to further clear MRD, which in turn translates into survival benefits. Daratumumab is a humanized, anti-CD38 IgG1 monoclonal antibody that binds to CD38 expressed by tumor cells. Apoptosis of tumor cells is induced through a variety of immune-related mechanisms such as complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cytophagocytosis (ADCP), and FCγ receptors, which are currently mainly used in the treatment of multiple myeloma. CD38 is highly and stably expressed on the surface of T-ALL cells, and its expression was less influenced by the previous treatment. Preliminary data from the clinical study of daratumumab combined with BFM bone frame prescription for the treatment of recurrent refractory T ALL(NCT03384654) showed that the effectiveness rate (ORR) was 83.3% in children and 60% in young adults. Compared with the previous historical data, the safety and tolerability were significantly improved. For T-ALL patients who relapse after allogeneic transplantation and achieve CR with intense chemotherapy but continue to have MRD-positive flow rate, daratumumab monotherapy can further clear MRD and achieve the purpose of sustaining CR. These studies all demonstrate the potential role of daratumumab in the treatment of T-ALL. Based on the current difficulties in the treatment of T-ALL and existing research data, we plan to conduct a prospective, single-arm, open-label phase II clinical study to explore the efficacy and safety of daratumumab for flow minimal residual disease positive T-ALL after standard chemotherapy.

Study Overview

• Status: Withdrawn
• Conditions: ALL, Adult
• Intervention / Treatment: Drug: Daratumumab Injection

Detailed Description

Daratumumab is administered once a week at a dose of 16 mg/kg for a total of 4 times (Day1,8,15,22) in one cycle. Conditions patients can use up to two cycles of treatment.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with newly diagnosed T-cell acute lymphoblastic leukemia confirmed by cell morphology and immunophenotype had flow MRD≥0.01% 3 months after chemotherapy; or patients with T-cell acute lymphoblastic leukemia relapsed achieved CR again after salvage chemotherapy, but the flow MRD was ≥0.01%
2. Age ≥18 years old, male or female
3. The expression of CD38 in tumor cells was positive
4. Men and women who may give birth agree to and use effective contraceptive methods
5. Main organ function assessment criteria: total bilirubin < 1.5× upper normal limit (ULN), glutamic oxalic aminotransferase (AST) and glutamic alanine aminotransferase (ALT) ≤2.5×ULN; Serum creatinine < 2×ULN; Myocardial enzyme < 2×ULN; Serum amylase ≤1.5×ULN; Left ventricular ejection fraction (LEF) was > 45%
6. Understand and sign the informed consent and agree to comply with the study requirements

Exclusion Criteria:

1. SAEs related to the study emerged during the study, and the investigator judged that the necessity of quitting the project was greater than the benefit
2. In case of any situation in which the subjects could not tolerate the study regimen, the investigator assessed that the necessity of withdrawal from the regimen outweighed the benefit
3. The subject had an allergic reaction to any drug of the study regimen or other conditions that prevented the regimen from continuing
4. Subjects voluntarily asked to withdraw from the study at any time
5. Any situation in which the investigator determines that the benefit of withdrawing from the study outweighs the benefit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Daratumumab; Daratumumab was administered once a week at a dose of 16 mg/kg for a total of 4 times (Day1,8,15,22 dosing patterns) in one cycle. Patients with conditions may use up to two cycles of treatment.	Drug: Daratumumab Injection; Daratumumab was administered once a week at a dose of 16 mg/kg for a total of 4 times (Day1,8,15,22 ) in one cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of conversion from MRD+to MRD- by flow cytometry after 1 cycle of daretuzumab treatment	If no abnormal phenotypic leukemia cells were detected by flow cytometry, flow MRD-negative was considered	up to 28days ±3days after daretuzumab treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day mortality	Percentage of patients who died within 30 days from enrollment	Within 30 days of the date of the last enrolled participants
60-day mortality	Percentage of patients who died within 60 days from enrollment	Within 60 days of the date of the last enrolled participants
overall survival overall survival 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
Disease-free survival (DFS)	Only for CR patients who chieved CR. The interval from the date of CR1 to relapse, death from any cause or last follow-up.	up to 2 years after the date of the last enrolled participants
Cumulative incidence of relapse (CIR)	Calculated with the cumulative incidence method, with death in patients who had a complete hematologic response as a competing risk.	up to 2 years after the date of the last enrolled participants
duration of MRD-negative response	No blasts were detected by flow cytometry after daretuzumab treatment	up to 2 years after the date of the last enrolled participants
Rate of conversion from MRD+to MRD- by NGS	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	up to 2 years after the date of the last enrolled participants

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Investigators: Principal Investigator: Hui Wei, doctor, Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: August 22, 2024
• First Submitted That Met QC Criteria: August 22, 2024
• First Posted (Actual): August 26, 2024

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; Antineoplastic Agents; daratumumab
• Other Study ID Numbers: IIT2024056

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
• product manufactured in and exported from the U.S.: No