Starting soon
Phase 1
Safety and Efficacy of DIT101 in Relapsed or Refractory Hematologic Malignancies
Condition(s) studied
Relapsed or Refractory Hematologic Malignancies
Investigational drug(s) / intervention(s)
In Vivo CAR-T Therapy
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.
Study summary
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.
Eligibility
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.
Primary outcome measure(s)
- Safety#Incidence and severity of adverse events (AEs) — 2 years after completion of the DIT101 infusion or until death, whichever occurs first.
To evaluate the possible adverse events after DIT101 infusion, including the incidence, and severity of AEs
- Safety#Incidence of Dose Limiting Toxicity (DLT) — 28 days after the first DIT101 infusion.
Incidence of dose limiting toxicities (DLTs) within 28 days after the first DIT101 infusion.
Trial sites (1)
| Facility | City | Region | Status |
|---|
| Hematology Hospital of Chinese Academy of Medical Sciences (Hematology Research Center of Chinese Academy of Medical Sciences) |
Tianjin |
China |
|
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