Clinical trial NCT05827835: CD7 CAR-T Bridging to alloHSCT for R/R CD7+Malignant Hematologic Diseases
Official title: A Study to Evaluate the Efficacy and Safety of CD7CAR-T Bridging to Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Refractory or Relapsed CD7 Positive Malignant Hematologic Diseases
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hematologic Diseases
Neoplasms
Keywords: allo-HSCT
CD7 CAR-T
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Yake Biotechnology Ltd.
First posted: 2023-04-25
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-arm, open-label, single-center, phase I 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


Eligibility criteria: Inclusion Criteria:

* Provision of signed and dated informed consent form (ICF)
* Male or female, 18-75 years old
* 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.

Primary outcomes:
measure: Incidence and level of AE and SAE
timeFrame: Baseline up to 28 days after CD7 CAR T-cells infusion
Secondary outcomes:
measure: CAR-T cell expression
timeFrame: Evaluate at 1, 2, 3, 4, 8,12,16, 20 and 24 weeks after CAR-T infusion
measure: CAR-T related cytokine expression
timeFrame: Evaluate at 1, 2, 3 and 4 weeks after CAR-T infusion
measure: Survival Rate （SR）
timeFrame: Evaluate at 6, 9, and 12 months
measure: Time-To-Progression（TTP）
timeFrame: Month 2,3,4,6,12,18and 24
measure: Progression-free survival (PFS)
timeFrame: Month 6,12,18and 24
measure: Duration of remission,DOR
timeFrame: Up to 1 years after Treatment
measure: Overall response rate,ORR
timeFrame: Evaluate at 4, 8, and 12 weeks after CAR-T infusion
measure: Clinical Benefit Rate（CBR）
timeFrame: Up to 24 weeks after Treatment
measure: Disease Control Rate （DCR）
timeFrame: Up to 12 weeks after Treatment
measure: Overall survival, OS
timeFrame: Up to 1 years after Treatment
measure: Minimal Residual Disease
timeFrame: Up to 2 years after Treatment
measure: Bone marrow transplantation STR
timeFrame: Evaluate at 4, 8,12,16 and 20 weeks after allogeneic hematopoietic stem cell transplantation
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The first affiliated hospital of medical college of zhejiang university
state: Zhejiang
Study officials:
affiliation: First Affiliated Hospital of Zhejiang University
name: He Huang, MD
role: PRINCIPAL_INVESTIGATOR
References: