Overview

A Study of CD20/CD22 Targeted CAR T-cell Therapy for Relapsed or Refractory Lymphoid Malignancies

Status:
Recruiting
Trial end date:
2028-05-23
Target enrollment:
0
Participant gender:
All
Summary
A Study of CD20/CD22 Targeted CAR T-cell Therapy for Relapsed or Refractory Lymphoid Malignancies.
Phase:
Early Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
He Huang
Collaborator:
Yake Biotechnology Ltd.
Criteria
Criteria:

Inclusion Criteria:

Inclusion criteria applicable to ALL only:

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;

Inclusion criteria applicable to NHL only:

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.