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

NCT ID: NCT04227015

Last Updated: 2020-12-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-08
• Study Completion Date: 2027-05-31

Brief Summary

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

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.

Conditions

Acute Lymphoblastic Leukemia; Non-hodgkin Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Administration of CTA101

Dose escalation follows the standard 3+3 dose escalation design. A total of 2 dose levels are set for subjects.

Group Type: EXPERIMENTAL

CTA101

Intervention Type: DRUG

CTA101 UCAR-T cell injection by intravenous infusion

Interventions

CTA101

CTA101 UCAR-T cell injection by intravenous infusion

Intervention Type: DRUG

Other Intervention Names

CTA101 UCAR-T cell injection

Eligibility Criteria

Inclusion Criteria

1. Male or female aged ≥ 3 and <70 years old;

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. Ineffective after first or multiple remedial treatments;

4. 2 or more recurrences;

4. The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is >5% (morphology) and/or >1% (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;

1. Male or female aged ≥ 18 and <70 years old;

2. 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;

3. Relapsed or refractory DLBCL (meeting one of the following conditions):

1. No remission or recurrence after receiving second-line or above second-line chemotherapy;

2. Primary drug resistance;

3. Recurrence after autologous hematopoietic stem cell transplantation

4. According to Lugano 2014, there should be at least one evaluable tumor lesion.

Applicable standards for ALL and NHL:

1. HLA antibody(-) or HLA antibody(+) and HLA donor specific antibody(DSA)(-);

2. total bilirubin ≤ 51umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8umol/L;

3. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%;

4. No active infection in the lungs, blood oxygen saturation by sucking air is ≥ 92%;

5. Estimated survival time ≥ 3 months;

6. ECOG performance status 0 to 2;

7. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion Criteria

1. patients with extramedullary lesions, except those with CNSL (CNS-1) under effective control (for ALL patients only);

2. Confirmed diagnosis of lymphoblastic crisis of chronic myeloid leukemia, Burkitt's leukemia/lymphoma per WHO Classification Criteria (for ALL patients only);

3. Patients with hereditary syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome (for ALL patients only);

4. patients with intracranial extralateral lesions (cerebrospinal fluid tumor cells and/or intracranial lymphoma invasion shown by MRI) (for NHL patients only) ;

5. extensive involvement of gastrointestinal lymphoma (for NHL patients only);

6. radiotherapy, chemotherapy and monoclonal antibody within 1 week before screening;

7. Have a history of allergy to any of the components in the cell products;

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

9. According to the New York heart association (NYHA) cardiac function classification criteria, Subjects with grade III or IV cardiac insufficiency;

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

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

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

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

14. Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis).

15. 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;

16. 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;

17. Patients with autoimmune diseases requiring treatment, patients with immunodeficiency or requiring immunosuppressive therapy;

18. Patients with graft-versus-host disease (GVHD);

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

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

21. 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;

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

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

24. pregnant and breast-feeding women and the subjects who are fertile and unable to take effective contraceptive measures (regardless of the gender);

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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nanjing Bioheng Biotech Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

He Huang

OTHER

Sponsor Role: lead

Responsible Party

He Huang

Clinical Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

The First Hospital of Zhejiang Medical Colleage Zhejiang University

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Facility Contacts

He Huang, MD

Role: primary

Jimin Shi, MD

Role: backup

Other Identifiers

BHCT-CTA101-08

Identifier Type: -

Identifier Source: org_study_id