A Study of CT-RD06 Cell Injection in Patients With Relapsed or Refractory CD19+ B-cell Hematological Malignancy

Study Overview
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Brief Summary
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A study of CT-RD06 cell injection in patients with relapsed or refractory CD19+ B-cell 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-cell hematological malignancy: B-ALL and B-NHL, the selections of dose levels and the number of subjects are based on clinical trials 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 CT-RD06 Cell Injection in Patients With Relapsed or Refractory CD19+ B-cell Hematological Malignancy

Conditions
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Acute Lymphoblastic Leukemia, Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Biological: CT-RD06


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria only for B-ALL: Male or female aged 3-70 years; 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; Ineffectively after first or multiple remedial treatments; 2 or more relapses; The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is﹥5% (by morphology), and/or﹥1% (by 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 only for B-NHL: Male or female aged 18-70 years; Histologically confirmed diagnosis of DLBCL (NOS), FL, DLBCL transformed from CLL/SLL, PMBCL, and HGBCL per the WHO Classification Criteria for Lymphoma (2016); Relapsed or refractory B-NHL (meeting one of the following conditions): No response or relapse after second-line or above chemotherapy regimens; Primary drug resistance; Relapse after auto-HSCT; At least one assessable tumor lesion per Lugano 2014 criteria; Common inclusion criteria for B-ALL and B-NHL: Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8 umol/L; Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%; No active infection in the lungs, blood oxygen saturation in indoor 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: Inclusion exclusion criteria only for B-ALL: Extramedullary lesions, except that CNSL (CNS-1) has been effectively controlled; Confirmed diagnosis of lymphoblastic crisis of chronic myeloid leukemia, Burkitt's leukemia/ lymphoma per WHO Classification Criteria; Hereditary syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome; Inclusion exclusion criteria only for B-NHL: Extranodal lesions in the brain (tumor cells in CSF, and/or MRI shows invasion of intracranial lymphoma); Extensive invasion of gastrointestinal lymphoma; Common exclusion criteria for B-ALL and B-NHL: History of hypersensitivity to any component of cell product; Prior treatment with any CAR T cell product or other genetically-modified T cell therapies; Prior treatment with radiotherapy, chemotherapy or mAb 1 week prior to apheresis; New York Heart Associate (NYHA) Class III/IV cardiac insufficiency (see Appendix 1); 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; 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; Autoimmune diseases requiring treatment, immunodeficiency or patients requiring immunosuppressive therapy; 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 and HIV 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; Female pregnant or lactating, male for female fertile but unable to take medically acceptable contraception measures; 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 CT-RD06<br>Dose escalation follows the standard 3+3 dose escalation design. A total of 3 dose levels are set for subjects. | Biological: CT-RD06<br>* CT-RD06 cell injection by intravenous infusion<br>* Other names: CT-RD06 CAR-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 CT-RD06 infusion | 
| Incidence of treatment-emergent adverse events (TEAEs) | Incidence of treatment-emergent adverse events [Safety and Tolerability] | Up to 2 years after CT-RD06 infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| B-cell acute lymphocytic leukemia(B-ALL), Overall response rate (ORR) | Assessment of ORR (ORR = CR + CRi ) at Month 6, 12, 18 and 24 | At Month 1, 3, 6, 12, 18 and 24 | 
| B-ALL, Overall survival (OS) | From the first infusion of CT-RD06 to death or the last visit | Up to 2 years after CT-RD06 infusion | 
| B-ALL, Event-free survival (EFS) | From the first infusion of CT-RD06 to the occurrence of any event, including death, relapse or gene relapse, disease progression (any one occurs first), and the last visit | Up to 2 years after CT-RD06 infusion | 
| B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR) | Assessment of ORR (ORR = CR + PR) per Lugano 2014 criteria | At Week 4, 12, and Month 6, 12, 18, 24 | 
| B-NHL, disease control rate (DCR) | Assessment of DCR (DCR=CR+PR+SD) per Lugano 2014 criteria | At Week 12 and Month 6, 12, 18, 24 |