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

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04226989
• Other study ID #: BHCT-CT-RD06-03
• Status: Recruiting
• Phase: Early Phase 1
• Start date: February 5, 2020
• Est. completion date: May 31, 2024

Study information

• Verified date: February 2020
• Source: Zhejiang University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A study of CT-RD06 cell injection in patients with relapsed or refractory CD19+ B-cell hematological malignancy.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: May 31, 2024
• Est. primary completion date: February 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 70 Years

Eligibility

Inclusion Criteria:

• Inclusion criteria only for B-ALL:

1. Male or female aged 3-70 years;

2. Histologically confirmed diagnosis of CD19+ B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1);

3. Relapsed or refractory CD19+ B-ALL (meeting one of the following conditions):

1. CR not achieved after standardized chemotherapy;

2. CR achieved following the first induction, but CR duration is = 12 months;

3. Ineffectively after first or multiple remedial treatments;

4. 2 or more relapses;

4. The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is?5% (by morphology), and/or?1% (by flow cytometry);

5. 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:

1. Male or female aged 18-70 years;

2. Histologically confirmed diagnosis of DLBCL (NOS), FL, DLBCL transformed from CLL/SLL, PMBCL, and HGBCL per the WHO Classification Criteria for Lymphoma (2016);

3. Relapsed or refractory B-NHL (meeting one of the following conditions):

1. No response or relapse after second-line or above chemotherapy regimens;

2. Primary drug resistance;

3. Relapse after auto-HSCT;

4. At least one assessable tumor lesion per Lugano 2014 criteria;

• Common inclusion criteria for B-ALL and B-NHL:

1. Total bilirubin = 51 umol/L, ALT and AST = 3 times of upper limit of normal, creatinine = 176.8 umol/L;

2. Echocardiogram shows left ventricular ejection fraction (LVEF) = 50%;

3. No active infection in the lungs, blood oxygen saturation in indoor air is = 92%;

4. Estimated survival time = 3 months;

5. ECOG performance status 0 to 2;

6. 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:

1. Extramedullary lesions, except that CNSL (CNS-1) has been effectively controlled;

2. Confirmed diagnosis of lymphoblastic crisis of chronic myeloid leukemia, Burkitt's leukemia/ lymphoma per WHO Classification Criteria;

3. 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:

1. Extranodal lesions in the brain (tumor cells in CSF, and/or MRI shows invasion of intracranial lymphoma);

2. Extensive invasion of gastrointestinal lymphoma;

• Common exclusion criteria for B-ALL and B-NHL:

1. History of hypersensitivity to any component of cell product;

2. Prior treatment with any CAR T cell product or other genetically-modified T cell therapies;

3. Prior treatment with radiotherapy, chemotherapy or mAb 1 week prior to apheresis;

4. New York Heart Associate (NYHA) Class III/IV cardiac insufficiency (see Appendix 1);

5. Myocardial infarction, cardioangioplasty or stenting, unstable angina pectoris, or other severe cardiac diseases within 12 months of enrollment;

6. Severe primary or secondary hypertension of grade 3 or above (WHO Hypertension Guidelines, 1999);

7. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;

8. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;

9. Severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);

10. 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;

11. History of other primary cancer, except for the following conditions:

1. Cured non-melanoma after resection, such as basal cell carcinoma of the skin;

2. Cervical cancer in situ, localized prostate cancer, ductal cancer in situ with disease-free survival = 2 years after adequate treatment;

12. Autoimmune diseases requiring treatment, immunodeficiency or patients requiring immunosuppressive therapy;

13. Prior immunizations with live vaccine 4 weeks prior to screening;

14. History of alcoholism, drug abuse or mental illness;

15. 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;

16. Concurrent therapy with systemic steroids within 1 week prior to screening, except for the patients recently or currently receiving inhaled steroids;

17. Patients who have participated in any other clinical studies within 2 weeks prior to screening;

18. Female pregnant or lactating, male for female fertile but unable to take medically acceptable contraception measures;

19. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Non-Hodgkin's Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• CT-RD06
CT-RD06 cell injection by intravenous infusion

Locations

Country	Name	City	State
China	The First Hospital of Zhejiang Medical Colleage Zhejiang University	Hangzhou	Zhejiang

Sponsors (2)

Lead Sponsor	Collaborator
He Huang	Nanjing Bioheng Biotech Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity (DLT)	Adverse events assessed according to NCI-CTCAE v5.0 criteria	Baseline up to 28 days after CT-RD06 infusion
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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