Safety and Efficacy of DIT101 in Relapsed or Refractory Hematologic Malignancies

Официальное название

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

Обзор

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.

Вмешательства

• Биопрепарат 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.

Первичные конечные точки

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

Вторичные конечные точки (6)

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

Критерии участия

Критерии включения

• 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).

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

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

Идентификаторы

NCT: NCT07485504 · DIT101-IBL001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗