Hematologic Diseases, Neoplasms
Conditions
Keywords
allo-HSCT, CD7 CAR-T
Brief summary
This is a single-arm, open-label, single-center, phase I/II study. The primary objective is to evaluate the safety of CD7 CAR-T Bridging to allo-HSCT therapy for patients with CD7-positive relapsed or refractory Malignant Hematologic Diseases
Interventions
CD7 CAR T cells treat patients with refractory or relapsed CD7 positive Malignant Hematologic Diseases
OTHERAllogeneic hematopoietic stem cell transplantation
In this study, Allogeneic hematopoietic stem cell transplantation is used as a bridge therapy to CD7 CAR T cells infusion to treat patients with refractory or relapsed CD7 positive Malignant Hematologic Diseases
Sponsors
Yake Biotechnology Ltd.
Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of signed and dated informed consent form (ICF) * Male or female, older than 18 years (including 18 years) * Anticipated survival time more than 12 weeks * Eastern Cooperative Oncology Group (ECOG) performance status ≤2 * According to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphocytic Leukemia and Acute Myeloid Leukemia (2016. v1), patients diagnosed as CD7+ALL and AML * Consistent with r/r CD7+acute leukemia diagnosis, including any of the following conditions * a. No CR after standard chemotherapy * b. The first induction reaches CR, but CR ≤ 12 months * c. Patients with r/r CD7+acute leukemia have not responded to the first or multiple remedial treatments * d. Multiple recurrences * Philadelphia chromosome negative (Ph -) subjects; Or cannot tolerate tyrosine kinase inhibitor (TKI) treatment; Or Philadelphia chromosome positive (Ph+) subjects who did not respond to both TKI treatments * Normal lung function, oxygen saturation greater than 92% without oxygen inhalation * The blood biochemical test results are consistent with the following results * a. (AST) and (ALT) ≤ 2.5 × (ULN) * b. Total bilirubin ≤ 1.5 × ULN * c. 24-hour serum creatinine clearance ≥ 30 mL/min * d. Lipase and amylase ≤ 2 × ULN * Fertility capable men and women of childbearing age must agree to use effective contraception starting with the signing of an informed consent form until within 2 years after the use of the study drug. Women of reproductive age include pre menopausal women and women within 2 years after menopause. The blood pregnancy test for women of reproductive age must be negative at screening
Exclusion criteria
* Patients with the history of epilepsy or other CNS disease * Pregnant or breastfeeding * Active infection with no cure * Patients with prolonged QT interval time or severe heart disease * Have experienced hypersensitivity or intolerance to any drug used in this study * Patients who received anticancer chemotherapy or other drug treatment within 2 weeks before screening * Previous malignant tumors that require treatment or have evidence of recurrence within the previous 5 years of screening * Clinically significant central nervous system lesions such as seizures, cerebral vascular ischemia/hemorrhage, dementia, cerebellar disease, psychosis, active central nervous system involvement, or cancerous meningitis * In the past 2 years, terminal organ damage caused by autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) or the need for systematic application of immunosuppressive or other systemic disease control drugs * Severe active viral, bacterial, or uncontrolled systemic fungal infections; Genetic bleeding/coagulation disorders, a history of non-traumatic bleeding or thromboembolism, and other diseases that may increase the risk of bleeding * Patients who received autologous hematopoietic stem cell transplantation (ASCT) within 8 weeks before screening, or who plan to undergo ASCT during this study * Participated in clinical trials of other drugs within 4 weeks or 5 drug half-lives (T1/2) before screening * Any situation that the researchers believe may increase the risk of patients or interfere with the test results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and level of AE and SAE | Baseline up to 28 days after CD7 CAR T-cells infusion | Adverse events assessed according to NCI-CTCAE v5.0 criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CAR-T related cytokine expression | Evaluate at 1, 2, 3 and 4 weeks after CAR-T infusion | CAR-T related cytokine expression |
| Survival Rate （SR） | Evaluate at 6, 9, and 12 months | Survival Rate （SR） |
| Time-To-Progression（TTP） | Month 2,3,4,6,12,18and 24 | Time from the beginning of treatment to the progression of the disease |
| Progression-free survival (PFS) | Month 6,12,18and 24 | Assessment of PFS at Month 6,12,18and 24 |
| Duration of remission,DOR | Up to 1 years after Treatment | The time from CR/CRi and PR to disease relapsed or death due to disease progression after CAR-T infusion |
| CAR-T cell expression | Evaluate at 1, 2, 3, 4, 8,12,16, 20 and 24 weeks after CAR-T infusion | CAR-T cell expression in vivo |
| Clinical Benefit Rate（CBR） | Up to 24 weeks after Treatment | ORR+MR |
| Disease Control Rate （DCR） | Up to 12 weeks after Treatment | CBR+SD |
| Overall survival, OS | Up to 1 years after Treatment | The time from CAR-T infusion to death due to any cause |
| Minimal Residual Disease | Up to 2 years after Treatment | MRD in CR and sCR patients |
| Bone marrow transplantation STR | Evaluate at 4, 8,12,16 and 20 weeks after allogeneic hematopoietic stem cell transplantation | Monitoring the status of allogeneic hematopoietic stem cell transplantation using STR-PCR |
| Overall response rate,ORR | Evaluate at 4, 8, and 12 weeks after CAR-T infusion | The proportion of patients with CR (complete remission) /CRi (complete remission with incomplete blood count recovery); The proportion of patients with CR (complete response) /CRi (complete response with incomplete blood cell recovery) and PR (partial response). |
Countries
China
Contacts
Primary ContactHe Huang, MD
Backup ContactYongxian HU, MD
Outcome results
None listed