A Study of CTA101 UCAR-T Cell Injection in Patients With Relapsed or Refractory CD19+ B-line Hematological Malignancy
Study Details
Study Description
Brief Summary
A study of CTA101 UCAR-T cell injection in patients with relapsed or refractory CD19+ B-line hematological malignancy
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Early Phase 1 |
Detailed Description
This is a single arm, open-label, single-center study. This study is indicated for relapsed or refractory CD19+ B-line hematological malignancy: B-ALL and B-NHL. the selection of dose levels and the number of subjects are based on clinical tiral of similar foreign products. 2 groups of patients will be enrolled, 36 in each group. Primary objective is to explore the safety, main consideration is dose-related safety.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Administration of CTA101 Dose escalation follows the standard 3+3 dose escalation design. A total of 2 dose levels are set for subjects. |
Drug: CTA101
CTA101 UCAR-T cell injection by intravenous infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Dose-limiting toxicity (DLT) [Baseline up to 28 days after CTA101 infusion]
Adverse events assessed according to NCI-CTCAE v5.0 criteria
- Incidence of treatment-emergent adverse events (TEAEs) [Up to 2 years after CTA101 infusion]
Incidence of treatment-emergent adverse events [Safety and Tolerability]
Secondary Outcome Measures
- B-cell acute lymphocytic leukemia (B-ALL), MRD negative overall response rate (MRD- ORR) [3 months]
Assessment of MRD negative overall response rate (MRD- ORR) at 3 months after CTA101 infusion
- B-ALL, Event-free survival (EFS) [Month 6, 12, 18 and 24]
From the first infusion of CTA101 to the occurrence of any event, including death, relapse or gene relapse, disease progression (any one occurs first), and the last visit
- B-ALL, Overall response rate (ORR) [Month 6, 12, 18 and 24]
Assessment of ORR (ORR = CR + CRi ) at Month 6, 12, 18 and 24
- B-ALL, Overall survival (OS) [Month 6, 12, 18 and 24]
From the first infusion of CTA101 to death or the last visit
- B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR) [weeks 4, 12, months 6, 12, 18 and 24]
Assessment of ORR (ORR = CR + PR ) per Lugano 2014 criteria
- B-NHL,disease control rate (DCR) [weeks 12, months 6, 12, 18 and 24]
Assessment of DCR (DCR=CR+PR+SD) per Lugano 2014 criteria
Eligibility Criteria
Criteria
Inclusion Criteria:
Inclusion criteria applicable to ALL only:
-
Male or female aged ≥ 3 and <70 years old;
-
Histologically confirmed diagnosis of CD19+ B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1);
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Relapsed or refractory CD19+ B-ALL (meeting one of the following conditions):
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CR not achieved after standardized chemotherapy;
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CR achieved following the first induction, but CR duration is ≤ 12 months;
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Ineffective after first or multiple remedial treatments;
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2 or more recurrences;
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The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is >5% (morphology) and/or >1% (Flow cytometry);
-
Philadelphia-chromosome-negative (Ph-) patients; or Philadelphia-chromosome-positive (Ph+) patients who cannot tolerate TKI treatments or do not respond to 2 TKI treatments;
Inclusion criteria applicable to NHL only:
-
Male or female aged ≥ 18 and <70 years old;
-
Histologically confirmed diagnosis per WHO Classification Criteria for Lymphocytic Tumors 2016, including DLBCL(NOS), follicular lymphoma, Chronic lymphoblastic leukemia/small lymphoblastic lymphoma transforms DLBCL, PMBCL and high grade B cell lymphoma;
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Relapsed or refractory DLBCL (meeting one of the following conditions):
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No remission or recurrence after receiving second-line or above second-line chemotherapy;
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Primary drug resistance;
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Recurrence after autologous hematopoietic stem cell transplantation
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According to Lugano 2014, there should be at least one evaluable tumor lesion.
Applicable standards for ALL and NHL:
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HLA antibody(-) or HLA antibody(+) and HLA donor specific antibody(DSA)(-);
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total bilirubin ≤ 51umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8umol/L;
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Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%;
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No active infection in the lungs, blood oxygen saturation by sucking air is ≥ 92%;
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Estimated survival time ≥ 3 months;
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ECOG performance status 0 to 2;
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Patients or their legal guardians volunteer to participate in the study and sign the informed consent.
Exclusion Criteria:
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patients with extramedullary lesions, except those with CNSL (CNS-1) under effective control (for ALL patients only);
-
Confirmed diagnosis of lymphoblastic crisis of chronic myeloid leukemia, Burkitt's leukemia/lymphoma per WHO Classification Criteria (for ALL patients only);
-
Patients with hereditary syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome (for ALL patients only);
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patients with intracranial extralateral lesions (cerebrospinal fluid tumor cells and/or intracranial lymphoma invasion shown by MRI) (for NHL patients only) ;
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extensive involvement of gastrointestinal lymphoma (for NHL patients only);
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radiotherapy, chemotherapy and monoclonal antibody within 1 week before screening;
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Have a history of allergy to any of the components in the cell products;
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Prior treatment with any CAR T cell product or other genetically-modified T cell therapies;
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According to the New York heart association (NYHA) cardiac function classification criteria, Subjects with grade III or IV cardiac insufficiency;
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Myocardial infarction, cardioangioplasty or stenting, unstable angina pectoris, or other severe cardiac diseases within 12 months of enrollment;
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Severe primary or secondary hypertension of grade 3 or above (WHO Hypertension Guidelines, 1999);
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Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
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History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;
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Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis).
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Indwelling catheters in vivo (e.g. percutaneous nephrostomy, Foley catheter, bile duct catheter, or pleural/peritoneal/pericardial catheter). Ommaya storage, dedicated central venous access catheters such as Port-a-Cath or Hickman catheters are allowed;
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History of other primary cancer, except for the following conditions:
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Cured non-melanoma after resection, such as basal cell carcinoma of the skin;
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Cervical cancer in situ, localized prostate cancer, ductal cancer in situ with disease-free survival ≥ 2 years after adequate treatment;
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Patients with autoimmune diseases requiring treatment, patients with immunodeficiency or requiring immunosuppressive therapy;
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Patients with graft-versus-host disease (GVHD);
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Prior immunizations with live vaccine 4 weeks prior to screening;
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History of alcoholism, drug abuse or mental illness;
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If HBsAg positive at screening, HBV DNA copy number detected by PCR in patients with active hepatitis B > 1000 (if HBV DNA copy number≤1000, routine antiviral therapy is required after enrollment), as well as CMV, hepatitis C, syphilis infection;
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Concurrent therapy with systemic steroids within 1 week prior to screening, except for the patients recently or currently receiving inhaled steroids;
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Patients who have participated in any other clinical studies within 2 weeks prior to screening;
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pregnant and breast-feeding women and the subjects who are fertile and unable to take effective contraceptive measures (regardless of the gender);
-
Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The First Hospital of Zhejiang Medical Colleage Zhejiang University | Hangzhou | Zhejiang | China | 310003 |
Sponsors and Collaborators
- He Huang
- Nanjing Bioheng Biotech Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BHCT-CTA101-08