Hematological Malignancies
Conditions
Keywords
UCAR-T
Brief summary
Primary Objective: To evaluate the safety, tolerability, and dose-limiting toxicity of anti-CD70 chimeric antigen receptor allogeneic T-cell injection (CHT101) in the treatment of CD70-positive relapsed/refractory T-cell and B-cell hematological malignancies. Secondary Objectives: To characterize the PK profiles of CHT101; to evaluate the clinical efficacy of CHT101 for CD70-positive relapsed/refractory T-cell and B-cell hematological malignancies. Indication: CD70-positive relapsed/refractory T-cell and B-cell hematological malignancies
Interventions
DRUGCHT101
Single-dose and multiple-dose administration Method of Administration: Intravenous infusion Dose of Administration:3.6\*10\^9 CAR-T cells,7.2\*10\^9 CAR-T cells,10\*10\^9 CAR-T cells.
Sponsors
Nanjing Miracle Biotechnology Co., Ltd.
Jiangxi Provincial Cancer Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Understand and voluntarily provide written informed consent (ICF) prior to any study-related assessments/procedures; 2. Aged between 18 and 70 years (inclusive) at the time of ICF signing; 3. CD70-positive tumor cells detected in bone marrow or peripheral blood by flow cytometry, or positive CD70 immunohistochemistry in tumor tissue; 4. Subjects with relapsed/refractory T-cell malignancies with measurable disease as defined by modified Severity-Weighted Assessment Tool (mSWAT) score or peripheral blood tumor burden, or at least one measurable lesion identified by imaging (PET-CT or CT) according to Lugano criteria (lymph node lesion with any diameter \>1.5 cm; extranodal lesion with any diameter \>1.0 cm), and meeting the following criteria: relapsed/refractory peripheral T-cell lymphoma (including but not limited to peripheral T-cell lymphoma-not otherwise specified, angioimmunoblastic T-cell lymphoma, anaplastic large-cell lymphoma, adult T-cell leukemia/lymphoma) or cutaneous T-cell lymphoma (including but not limited to mycosis fungoides or Sézary syndrome \[stage IIB or higher with disease involving two or more regions, or single-region disease with large-cell transformation\]), and having received prior systemic therapy: subjects with peripheral T-cell lymphoma shall have received at least one line of therapy; subjects with cutaneous T-cell lymphoma shall have received at least two lines of therapy; for anaplastic large-cell lymphoma (ALCL), subjects must have relapsed following prior brentuximab vedotin therapy, or relapsed after ≥2 prior therapies (if anaplastic lymphoma kinase-positive); 5. Subjects with relapsed/refractory B-cell malignancies with at least one measurable lesion and meeting at least one of the following criteria: * Indolent lymphoma (FL, MCL, MZL): relapsed or refractory after at least two prior lines of therapy containing a CD20 antibody; * Chronic lymphocytic leukemia (CLL): relapsed or refractory after at least two prior lines of therapy including BTK inhibitor and venetoclax; * Aggressive or highly aggressive lymphoma (DLBCL, Burkitt lymphoma, high-grade B-cell lymphoma \[double-hit, triple-hit, primary mediastinal DLBCL\]): relapsed or refractory after at least two prior lines of therapy containing a CD20 antibody and anthracycline, and the subject is ineligible for autologous stem-cell transplantation (conditions for ineligibility for autologous stem-cell transplantation include absence of disease response after salvage therapy, and failure of stem-cell mobilization precluding transplantation); * Acute lymphoblastic leukemia (ALL): relapsed or refractory after at least two prior lines of therapy; 6. Histopathologically confirmed classical Hodgkin lymphoma (cHL), relapsed or refractory (following BV and PD-1 therapy), with at least one measurable lesion per the Lugano 2014 lymphoma response evaluation criteria; 7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 at the time of ICF signing; 8. Expected survival of at least 12 weeks; 9. Fertile male subjects and female subjects of child-bearing potential must agree to use effective contraception from the time of ICF signing until 2 years after administration of investigational product. Female subjects of child-bearing potential include pre-menopausal women and women within 2 years post-menopause. Serum pregnancy test must be negative for female subjects of child-bearing potential at screening.
Exclusion criteria
1. Central nervous system (CNS) metastasis, leptomeningeal disease or metastatic central compression; or prior history of CNS diseases, including but not limited to epilepsy, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, etc.; 2. History of organ transplantation; 3. History of other primary malignancies within 5 years prior to study treatment, except for: a) adequately treated and cured carcinoma in situ of the cervix; b) localized basal-cell carcinoma or squamous-cell carcinoma of the skin; 4. Subjects with positive HBV DNA in peripheral blood at screening; subjects positive for hepatitis C virus (HCV) antibody with detectable peripheral blood HCV RNA; subjects positive for human immunodeficiency virus (HIV) antibody; subjects with both positive treponemal-specific antibody and non-treponemal antibody tests for syphilis; 5. Known allergy to any component of study medications, including but not limited to lymphodepleting agents (cyclophosphamide, fludarabine), contrast media for imaging examinations; 6. Prior anti-CD70 antitumor therapy, including but not limited to anti-CD70 cell therapy (autologous or allogeneic), TCR-T therapy, etc.; 7. Prior receipt of CAR-T therapy or other cell/gene therapy; 8. Presence of acute or moderate-to-severe chronic graft-versus-host disease (GVHD) within 4 weeks prior to ICF signing, or receipt of systemic medicinal treatment for GVHD within 4 weeks prior to first infusion; 9. Receipt of any investigational product or systemic antitumor therapy within 28 days prior to first infusion (or five half-lives of the drug, whichever is more appropriate at the investigator's discretion); 10. Receipt of extensive radiotherapy within 28 days prior to ICF signing, except for local radiotherapy for symptomatic relief of non-target lesions administered within 14 days prior to ICF signing or anticipated during the study period; 11. Major surgical procedure within 28 days prior to ICF signing, or anticipated major surgical procedure during the study period; 12. Any uncontrolled active infection requiring parenteral antibiotic, antiviral or antifungal therapy at the time of ICF signing or within 4 weeks prior to first infusion; 13. History of active pulmonary tuberculosis within 1 year before screening (except for subjects with a history of active pulmonary tuberculosis more than 1 year earlier who are judged by the investigator to have no current evidence of active pulmonary tuberculosis); 14. Concurrent or prior history of interstitial lung disease or interstitial pneumonia; 15. Active or previously-occurred autoimmune diseases with potential for relapse (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vasculitis, psoriasis, etc.), or at risk for such diseases; 16. Requirement for systemic corticosteroids (≥10 mg/day prednisone equivalent) or other immunosuppressive agents within 2 weeks prior to ICF signing or during the study period, except for: a) intranasal, inhaled, topical steroids or local steroid injection (e.g., intra-articular injection); b) systemic corticosteroids at physiological doses ≤10 mg/day prednisone equivalent; c) steroids for prophylaxis against hypersensitivity reactions (e.g., premedication prior to computed tomography \[CT\]); 17. Clinically significant thyroid dysfunction as judged by the investigator; 18. Clinically significant cardiovascular disease, including any of the following: a) heart-rate-corrected QT interval (QTcF) \>470 msec; b) New York Heart Association (NYHA) class II or higher heart failure; c) left ventricular ejection fraction (LVEF) ≤50%; d) uncontrolled hypertension (systolic blood pressure ≥150 mm Hg and/or diastolic blood pressure ≥95 mm Hg); e) arrhythmias of clinical significance or requiring antiarrhythmic therapy (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes, complete left bundle-branch block, etc.); f) unstable angina or acute myocardial infarction within 6 months prior to ICF signing; 19. Insufficient bone marrow reserve or organ function meeting any of the following laboratory criteria: a) absolute neutrophil count \<1.5×10⁹/L; b) platelet count \<50×10⁹/L; c) hemoglobin \<70 g/L; d) abnormal coagulation parameters: international normalized ratio (INR) \>2.0 or prothrombin time (PT) \>1.5 × upper limit of normal (ULN); e) alanine aminotransferase (ALT) \>2.5 × ULN; f) aspartate aminotransferase (AST) \>2.5 × ULN; g) total bilirubin \>2.5 × ULN; h) serum creatinine clearance \<60 mL/min (calculated by the Cockcroft-Gault formula); 20. History of bleeding events within 6 months prior to ICF signing; clinically significant bleeding requiring medical intervention within 28 days before screening, including esophageal variceal bleeding; 21. Vaccination with live-attenuated/inactivated vaccines within 28 days prior to ICF signing, or planned administration of live-attenuated/inactivated vaccines during the screening period; 22. Subjects whose comorbidities or other circumstances, in the investigator's opinion, may impair protocol compliance or render the subject ineligible for study participation; 23. Female subjects who are pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose (MTD) | Day 28 |
| To assess the incidence, severity, and relatedness of adverse events (AEs) and serious adverse events (SAEs). | Throughout the study period, up to 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Peripheral blood CAR-T cell proportion | Day 1,Day 2,Day 4,Day 7,Day 11,Day 14,Day 18,Day 21,Day 28,Month 2,Month 3,Month 4,Month 5,Month 6,Month 9,Month 12,Month 15,Month 18,Month 21,Month 24 |
| ORR | Month 2,Month 3,Month 6,Month 9,Month 12,Month 18,Month 24 |
| DOR | Month 2,Month 3,Month 6,Month 9,Month 12,Month 18,Month 24 |
| PFS | Month 2,Month 3,Month 6,Month 9,Month 12,Month 18,Month 24 |
| OS | Month 2,Month 3,Month 6,Month 9,Month 12,Month 18,Month 24 |
| Peripheral blood CAR copy number | Day 1,Day 2,Day 4,Day 7,Day 11,Day 14,Day 18,Day 21,Day 28,Month 2,Month 3,Month 4,Month 5,Month 6,Month 9,Month 12,Month 15,Month 18,Month 21,Month 24 |
Countries
China
Contacts
CONTACTChao Dai
Outcome results
None listed