Clinical trial NCT04227015: A Study of CTA101 UCAR-T Cell Injection in Patients With Relapsed or Refractory CD19+ B-line Hematological Malignancy
Official title: A Study of CTA101 UCAR-T Cell Injection in Patients With Relapsed or Refractory CD19+ B-line Hematological Malignancy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Acute Lymphoblastic Leukemia
Non-hodgkin Lymphoma
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Nanjing Bioheng Biotech Co., Ltd.
First posted: 2020-01-13
Enrollment: 72
Sex: ALL
Minimum age (years): 3
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Baseline up to 28 days after CTA101 infusion
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 2 years after CTA101 infusion
Secondary outcomes:
measure: B-cell acute lymphocytic leukemia (B-ALL), MRD negative overall response rate (MRD- ORR)
timeFrame: 3 months
measure: B-ALL, Event-free survival (EFS)
timeFrame: Month 6, 12, 18 and 24
measure: B-ALL, Overall response rate (ORR)
timeFrame: Month 6, 12, 18 and 24
measure: B-ALL, Overall survival (OS)
timeFrame: Month 6, 12, 18 and 24
measure: B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR)
timeFrame: weeks 4, 12, months 6, 12, 18 and 24
measure: B-NHL,disease control rate (DCR)
timeFrame: weeks 12, months 6, 12, 18 and 24
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Hospital of Zhejiang Medical Colleage Zhejiang University
state: Zhejiang
Study officials:
References: