A Study of CTA101 UCAR-T Cell Injection in Patients With Relapsed or Refractory CD19+ B-line Hematological Malignancy

Study Overview
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Brief Summary
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A study of CTA101 UCAR-T cell injection in patients with relapsed or refractory CD19+ B-line hematological malignancy

Detailed Description
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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.

Official Title
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A Study of CTA101 UCAR-T Cell Injection in Patients With Relapsed or Refractory CD19+ B-line Hematological Malignancy

Conditions
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Acute Lymphoblastic Leukemia, Non-hodgkin Lymphoma

Intervention / Treatment
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* Drug: CTA101


Participation Criteria
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Eligibility Criteria
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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); Relapsed or refractory CD19+ B-ALL (meeting one of the following conditions): CR not achieved after standardized chemotherapy; CR achieved following the first induction, but CR duration is ≤ 12 months; Ineffective after first or multiple remedial treatments; 2 or more recurrences; 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; Relapsed or refractory DLBCL (meeting one of the following conditions): No remission or recurrence after receiving second-line or above second-line chemotherapy; Primary drug resistance; Recurrence after autologous hematopoietic stem cell transplantation According to Lugano 2014, there should be at least one evaluable tumor lesion. Applicable standards for ALL and NHL: HLA antibody(-) or HLA antibody(+) and HLA donor specific antibody(DSA)(-); total bilirubin ≤ 51umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8umol/L; Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%; No active infection in the lungs, blood oxygen saturation by sucking air is ≥ 92%; Estimated survival time ≥ 3 months; ECOG performance status 0 to 2; Patients or their legal guardians volunteer to participate in the study and sign the informed consent. Exclusion Criteria: 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); patients with intracranial extralateral lesions (cerebrospinal fluid tumor cells and/or intracranial lymphoma invasion shown by MRI) (for NHL patients only) ; extensive involvement of gastrointestinal lymphoma (for NHL patients only); radiotherapy, chemotherapy and monoclonal antibody within 1 week before screening; Have a history of allergy to any of the components in the cell products; Prior treatment with any CAR T cell product or other genetically-modified T cell therapies; According to the New York heart association (NYHA) cardiac function classification criteria, Subjects with grade III or IV cardiac insufficiency; Myocardial infarction, cardioangioplasty or stenting, unstable angina pectoris, or other severe cardiac diseases within 12 months of enrollment; Severe primary or secondary hypertension of grade 3 or above (WHO Hypertension Guidelines, 1999); Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past; History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases; Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis). 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; History of other primary cancer, except for the following conditions: Cured non-melanoma after resection, such as basal cell carcinoma of the skin; Cervical cancer in situ, localized prostate cancer, ductal cancer in situ with disease-free survival ≥ 2 years after adequate treatment; Patients with autoimmune diseases requiring treatment, patients with immunodeficiency or requiring immunosuppressive therapy; Patients with graft-versus-host disease (GVHD); Prior immunizations with live vaccine 4 weeks prior to screening; History of alcoholism, drug abuse or mental illness; 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; Concurrent therapy with systemic steroids within 1 week prior to screening, except for the patients recently or currently receiving inhaled steroids; Patients who have participated in any other clinical studies within 2 weeks prior to screening; 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.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Administration of CTA101<br>Dose escalation follows the standard 3+3 dose escalation design. A total of 2 dose levels are set for subjects. | Drug: CTA101<br>* CTA101 UCAR-T cell injection by intravenous infusion<br>* Other names: CTA101 UCAR-T cell injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | Adverse events assessed according to NCI-CTCAE v5.0 criteria | Baseline up to 28 days after CTA101 infusion | 
| Incidence of treatment-emergent adverse events (TEAEs) | Incidence of treatment-emergent adverse events [Safety and Tolerability] | Up to 2 years after CTA101 infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| B-cell acute lymphocytic leukemia (B-ALL), MRD negative overall response rate (MRD- ORR) | Assessment of MRD negative overall response rate (MRD- ORR) at 3 months after CTA101 infusion | 3 months | 
| B-ALL, Event-free survival (EFS) | 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 | Month 6, 12, 18 and 24 | 
| B-ALL, Overall response rate (ORR) | Assessment of ORR (ORR = CR + CRi ) at Month 6, 12, 18 and 24 | Month 6, 12, 18 and 24 | 
| B-ALL, Overall survival (OS) | From the first infusion of CTA101 to death or the last visit | Month 6, 12, 18 and 24 | 
| B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR) | Assessment of ORR (ORR = CR + PR ) per Lugano 2014 criteria | weeks 4, 12, months 6, 12, 18 and 24 | 
| B-NHL,disease control rate (DCR) | Assessment of DCR (DCR=CR+PR+SD) per Lugano 2014 criteria | weeks 12, months 6, 12, 18 and 24 |