Clinical Study of ssCART-19 Cells in Patients With CD19 Positive Relapsed or Refractory Acute Lymphoblastic Leukemia

Relapsed or Refractory Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Clinical Study of ssCART-19 Cells in Patients With CD19 Positive Relapsed or Refractory Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04825496
• Other study ID #: ssCART-19
• Status: Recruiting
• Phase: Phase 1
• Start date: April 9, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2023
• Source: Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd
• Contact: Xiaoyan Lou, Dr.
• Phone: 18721281671
• Email: xiaoyan.lou[@]unicar-therapy.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single arm, open-label, non-randomized, dose-escalation, phase I study to determine the safety and efficacy of ssCART-19 in the treatment of patients with CD19 positive relapsed or refractory acute lymphoblastic leukemia.

Description:

This is a single arm, open-label, non-randomized, dose-escalation, phase I study to determine the safety and efficacy of ssCART-19 in the treatment of patients with CD19 positive relapsed or refractory acute lymphoblastic leukemia. Primary objectives: Determine the safety and tolerability of ssCART-19 cells in patients with refractory or relapsed acute lymphoblastic leukemia. Secondary objectives: 1. Observe the anti-tumor response of ssCART-19 cells to refractory or relapsed acute lymphoblastic leukemia. - Overall remission rate (ORR) assessment during the 3 months after ssCART-19 administration，ORR includes CR and CRi - Duration of response (DOR) - Progression-free survival (PFS) - Overall survival (OS) 2. To characterize the in vivo cellular pharmacokinetic (PK) profile of ssCART-19 cells. 3. To characterize the pharmacodynamic (PD) profile of ssCART-19 cells.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Relapsed or refractory acute lymphoblastic leukemia (ALL):(1)Any Relaps after first remission OR (2)Any BM relapse after allogeneic SCT and must be = 3 months from SCT at the time of ssCART-19 infusion OR (3)failed to reach CR after 2 cycles of induction chemotherapy regimen OR (4)Patients with Ph+ ALL are eligible if they are intolerant to or have failed two lines of TKI therapy, or if TKI therapy is contraindicated

2. CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry

3. Bone marrow with = 5% lymphoblasts by morphologic assessment

4. Adequate organ function defined as:(1)left ventricular ejection fraction = 50% by echocardiogram;(2)creatinine = 1.6mg/dl;(3)ALT and AST=3 times the ULN for age, total bilirubin = 2.0mg/dl;(4)Must have a minimum level of pulmonary reserve defined as = Grade 1 dyspnea and pulse oxygenation > 91% on room air

5. Informed consent is signed by the subject

6. Age 18 to 65

7. Fertility of men, to ensure that sexual partners can effectively contraception; Women with fertility use effective contraceptive measures and agree to use contraceptive measures throughout the study period

8. Qualified T cell amplification

9. Eastern cooperative oncology group (ECOG) performance status of 0 to 1

10. Vascular conditions for apheresis

11. The estimated survival time is more than 3 months

Exclusion Criteria:

1. Isolated extra-medullary disease relapse

2. Combined with other malignant tumors

3. Has had treatment with any prior anti-CD19/anti-CD3 therapy, or any other antiCD19 therapy

4. Has had immunosuppressants or hormones within 2 weeks before signing informed consent, or plan to use immunosuppressants or hormones after signing informed consent

5. Patients complying with any of hepatitis B surface antigen (HBsAg) and/or hepatitis B e antigen (HBeAg) positive, hepatitis B e antibody (HBe-Ab) and/or hepatitis B core antibody (HBc-Ab) positive and HBV-DNA copies being more than the lower limit of detection, hepatitis C antibody (HCV-Ab) positive, anti-treponemia pallidum antibody (TP-Ab) positive, EBV-DNA, and CMV-DNA copies being more than the lower limit of detection

6. Has uncontrolled bacteria, fungi, viruses, mycoplasma or other types of infections

7. Infected with HIV, syphilis or COVID-19

8. Has a history of severe immediate hypersensitivity to aminoglycosides

9. Has past or present CNS diseases, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases or any CNS-related autoimmune diseases

10. Has undergone cardiac angioplasty or stent implantation within 12 months before signing informed consent, or having a history of myocardial infarction, unstable angina pectoris or other clinically significant heart diseases

11. With primary immunodeficiency

12. Has had severe immediate hypersensitivity reaction to any drug to be used in this study

13. Has had treat with live vaccine within 6 weeks prior to screening

14. Pregnant or lactating women

15. Has active autoimmune diseases

16. Has active acute or chronic graft-versus-host disease (GVHD) before signing informed consent

17. Patient has an investigational medicinal product within 3 months before signing informed consent

18. Patients with other conditions making the patients unsuitable for receiving cell therapy as judged by the investigator

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Relapsed or Refractory Acute Lymphoblastic Leukemia

Intervention

Genetic:
• ssCART-19 Cells
Split-Dose of ssCART-19 cells will be infused, and classic "3+3" dose escalation will be applied.

Drug:
• Fludarabine
Fludarabine is used for lymphodepletion.
• Cyclophosphamide
Cyclophosphamide is used for lymphodepletion.

Locations

Country	Name	City	State
China	Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd.	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd	The First Affiliated Hospital of Soochow University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	cellular pharmacokinetic (PK) profile of ssCART-19 cells	Number of DNA copies of ssCART-19 cells	24 months
Other	Anti-drug antibody	Detect titer of anti-drug antibody (ADA)	24 months
Primary	Dose Limiting Toxicity (DLT)	Determine the safety and tolerability of ssCART-19 in patients with refractory or relapsed acute lymphoblastic leukemia.; Safety measures include adverse events as assessed by CTCAE v5.0.	28 days
Secondary	Overall Remission Rate (ORR), which includes Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi)	Efficacy of ssCART-19 as measured by ORR during the 3 months after ssCART-19 infusion, which includes CR and CRi.	3 months
Secondary	Duration of remission (DOR)	Statistical parameter:Duration of remission (DOR)	24 months
Secondary	Progression-free Survival (PFS)	Statistical parameter:Progression-free Survival (PFS)	24 months
Secondary	Overall survival (OS)	Statistical parameter:Overall survival (OS)	24 months