Safety and Efficacy of DIT101 in Relapsed or Refractory Hematologic Malignancies

Official title

A Prospective, Single-Arm Study Evaluating the Safety and Efficacy of DIT101 in Subjects With Relapsed or Refractory Hematologic Malignancies

Overview

This study is a single-arm, open-label clinical trial designed to evaluate the safety and tolerability of DIT101 in adults with relapsed or refractory hematologic malignancies and to explore its potential anti-tumor effects. DIT101 is an investigational in vivo CAR-T cell therapy administered by intravenous infusion. After administration, it is intended to generate CAR-T cells within the patient's body that can recognize and attack tumor cells. Unlike approved autologous CAR-T therapies, DIT101 does not require collection and ex vivo genetic modification of the participant's own cells. The study includes a screening period, DIT101 infusion treatment, a post-treatment intensive follow-up period of approximately 6 months, and a long-term follow-up period of up to 2 years, with visits every 3-6 months.

Interventions

• Biological In Vivo CAR-T Therapy
  Participants will receive 1 intravenous administration of DIT101, according to the study dosing regimen. A second dose at the same dose may be administered to eligible participants who show no response after initial treatment, upon sponsor approval.

Primary outcome measures

• Safety#Incidence and severity of adverse events (AEs) [Time frame: 2 years after completion of the DIT101 infusion or until death, whichever occurs first.]
• Safety#Incidence of Dose Limiting Toxicity (DLT) [Time frame: 28 days after the first DIT101 infusion.]

Secondary outcome measures (6)

• Duration of Remission (DOR) [Time frame: 2 years after completion of the DIT101 infusion or until death, whichever occurs first.]
• Event-Free Survival (EFS) [Time frame: 2 years after completion of the DIT101 infusion or until death, whichever occurs first.]
• Leukemia-Free Survival (LFS) [Time frame: 2 years after completion of the DIT101 infusion or until death, whichever occurs first.]
• Proportion of Responding Subjects Receiving HSCT [Time frame: Up to 2 years following the completion of DIT101 infusion.]
• Overall Survival (OS) [Time frame: Up to 2 years after DIT101 infusion or until death, whichever occurs first.]
• Maximum Concentration (Cmax) of CAR-T Cells in Peripheral Blood [Time frame: up to 2 years after completion of the DIT101 infusion or until death, whichever occurs first.]

Eligibility criteria

Inclusion criteria

• Adults aged 18 to <70 years, any gender.
• Voluntarily provide written informed consent and willing to comply with all study procedures.
• Diagnosed with relapsed or refractory B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL), or other relapsed/refractory hematologic malignancies as judged by the investigator and confirmed by the collaborating institution.
• Tumor cells confirmed positive for the target antigen by immunophenotyping.
• Bone marrow blast ≥5% at screening and/or presence of extramedullary disease.
• For B-ALL/LBL patients, meets criteria for relapsed/refractory disease, including:

• Primary refractory after ≥2 cycles of standard chemotherapy or not achieving CR after multiple salvage regimens;
• Relapse within 12 months after CR or ≥12 months relapse after CR not achieving CR after subsequent standard therapy;
• Relapse after hematopoietic stem cell transplantation;
• Relapse after prior CAR-T therapy targeting the same antigen.
• ECOG performance status 0-2.
• Expected survival >3 months.
• Adequate organ function, including:

• Renal: creatinine clearance >45 mL/min;
• Hepatic: total bilirubin ≤3×ULN, ALT/AST ≤5×ULN;
• Coagulation: PT, APTT, or INR ≤1.5×ULN;
• Cardiac: LVEF ≥50% within 1 month;
• Pulmonary: SpO₂ ≥92% at rest on room air;
• Hematologic and immune function considered sufficient to tolerate study treatment.
• Women of childbearing potential must have a negative pregnancy test; women considered not of childbearing potential include those who are postmenopausal for ≥12 months or have undergone surgical sterilization (hysterectomy or bilateral oophorectomy).

Exclusion criteria

• Pregnant or breastfeeding women.
• Known hereditary bone marrow failure syndromes (e.g., Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or other known marrow failure syndromes).
• Uncontrolled active central nervous system leukemia (CNSL; CNS2 or CNS3).
• Prior anti-cancer therapy before screening, including:

• Systemic chemotherapy within 1 week;
• Systemic immunotherapy/targeted therapy (monoclonal antibodies, bispecific antibodies, ADCs, etc.) with last dose <5 half-lives or <4 weeks (whichever is shorter);
• Donor lymphocyte infusion within 6 weeks;
• CAR-T therapy or hematopoietic stem cell transplantation within 3 months;
• Radiotherapy within 4 weeks (unless bone marrow reserve >5% and investigator judges it does not affect eligibility);
• Persistent clinically significant toxicity from prior therapy not recovered to ≤CTCAE Grade 1 (except alopecia).
• Uncontrolled severe active infection.
• History of significant cardiac disease, including: severe heart failure (NYHA class III-IV), myocardial infarction or PCI/stent within 12 months, unstable angina, QTc >480 ms, or other clinically significant arrhythmia per investigator judgment.
• History of CNS injury, seizure, stroke, or brain hemorrhage requiring treatment within 6 months.
• Active viral infections:

• HIV antibody positive, syphilis serology positive;
• HBsAg >10⁶ IU/mL;
• HCV antibody positive;
• EBV positive (EBER or copy number above normal).
• Need for long-term systemic corticosteroid therapy during DIT-101 infusion (local or inhaled steroids allowed).
• Active autoimmune disease requiring treatment, immunodeficiency, or use of immunosuppressive therapy.
• Acute or moderate-to-severe chronic graft-versus-host disease (GvHD) within 4 weeks prior to screening.
• Known severe allergy to any component of DIT-101.
• Women of childbearing potential or men unable to use effective contraception during DIT-101 infusion and for 1 year post-infusion; plans for pregnancy within 1 year post-infusion in male or female subjects or their partners.
• Any condition that, in the investigator's opinion, may increase risk or interfere with study outcomes.
• Prior malignancy other than hematologic malignancy, except:

• Malignancy treated with curative intent and disease-free ≥2 years;
• Non-melanoma skin cancer adequately treated with no current evidence of disease.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Hematology Hospital of Chinese Academy of Medical Sciences (Hematology Research Center of — Tianjin

Identifiers

NCT: NCT07485504 · DIT101-IBL001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗