CD7 CAR-T therapy followed by allogeneic stem cell transplant for relapsed/refractory CD7-positive blood cancers

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

This will test whether CD7-directed CAR-T cells given before an allogeneic stem cell transplant are safe for adults with relapsed or refractory CD7-positive acute leukemias.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Zhejiang University (Academic / other)
• Drugs / interventions: chemotherapy, CAR-T
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT05827835 on ClinicalTrials.gov

What this trial studies

This single-arm, open-label, single-center phase I/II study gives adults with CD7-positive relapsed or refractory malignant hematologic diseases an infusion of CD7-directed CAR-T cells and, when appropriate, moves them on to allogeneic hematopoietic stem cell transplantation. The primary goal in phase I is to measure safety and tolerability of the CAR-T followed by transplant, while phase II will provide preliminary information on activity and feasibility of bridging to allo-HSCT. Patients will be closely monitored for adverse events, treatment response, and transplant-related outcomes at the First Affiliated Hospital of Zhejiang University in Hangzhou. As a single-center early-phase trial, it is intended to detect safety signals and inform larger studies rather than provide definitive efficacy proof.

Who should consider this trial

Good fit: Adults (≥18) with CD7-positive relapsed or refractory acute leukemias who meet transplant criteria, have ECOG ≤2, and an expected survival of at least 12 weeks.

Not a fit: Patients without CD7 expression, those who are medically unfit for transplant, have very limited life expectancy, or poor lung function are unlikely to benefit.

Why it matters

Potential benefit: If successful, this approach could control CD7-positive disease long enough to allow potentially curative allogeneic stem cell transplantation.

How similar studies have performed: Early-phase studies of CD7-targeted CAR-T cells have reported promising responses in CD7-positive leukemias, and using CAR-T as a bridge to allo-HSCT has precedent but remains experimental.

Eligibility criteria

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.

Where this trial is running

Hangzhou, Zhejiang

• The first affiliated hospital of medical college of zhejiang university — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: He Huang, MD — First Affiliated Hospital of Zhejiang University
• Study coordinator: He Huang, MD

Conditions Hematologic Diseases; Neoplasms; allo-HSCT; CD7 CAR-T