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

He Huang

Status and phase

Enrolling

Early Phase 1

Conditions

Non-Hodgkin's Lymphoma

Acute Lymphoblastic Leukemia

Treatments

Biological: CT-RD06

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT04226989

BHCT-CT-RD06-03

Details and patient eligibility

About

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

Full 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.

Enrollment

72 estimated patients

Sex

All

Ages

3 to 70 years old

Volunteers

No Healthy Volunteers

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.