Clinical trial NCT06445803: CD19/CD22 CAR-T Cells in Adults With R/R ALL or NHL
Official title: A Preliminary Study to Evaluate the Safety, Tolerability, Preliminary Efficacy and Pharmacokinetic Profile of KQ-2002 (CD19/CD22 CAR-T) in Adults With Recurrent or Refractory Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Acute Lymphoblastic Leukemia, in Relapse
Acute Lymphoblastic Leukemia With Failed Remission
B-cell Lymphoma Refractory
B-cell Lymphoma Recurrent
Keywords: CAR-T therapy
Lead sponsor: Fudan University
Sponsor class: OTHER
Collaborators: name: Novatim Immune Therapeutics (Zhejiang) Co., Ltd.
First posted: 2024-06-06
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study examines the safety, tolerability and preliminary efficacy of anti-CD19 /CD22 CAR T cells (KQ-2002)manufactured on-site in adults with relapsed or refractory CD19+ B cell acute lymphoblastic leukemia or CD19+ B cell non Hodgkin lymphoma.

Detailed description: Patients will undergo screening, leukapheresis (cell collection), lymphodepleting chemotherapy with fludarabine and cyclophosphamide, followed by the anti-CD19 KQ-2002 CAR T cell infusion. The lymphodepleting chemotherapy is administered over 3 days IV to prepare the body for the CAR T cells. The CAR-T cells are infused between 2-7 days after the last dose of chemotherapy. Patients will be followed for two years after the cell infusion on the study and for up to 15 years to monitor for potential long term side effects of cell therapy.

Eligibility criteria: Inclusion Criteria:

* Male or female,≥18 years old;
* Histologically confirmed diagnosis of B-ALL or B-NHL(meeting one of the following conditions):

(B-NHL)

1. Second or greater relapse (CD20 regimens must be included) OR
2. Refractory to first-line chemotherapy or relapse within 1 year OR
3. Relapse within 1 year of auto-HSCT.
4. With measurable or evaluable lesions（Dose expansion cohort） (B-ALL)

a. Relapse within 12 months of complete remission on first treatment OR b. Relapse after second-line treatment OR c. Relapse after auto HST OR d. Failure to achieve CR/CRi at the end of induction therapy OR e. Ph+ ALL intolerance to TKI or refractory or relapse after treatment with at least two and more TKIs.

* ECOG 0\~2
* Estimated survival time ≥ 12 weeks;
* Main tissues and organs function well.

Exclusion Criteria:

* Subjects will be excluded related to the following prior therapy criteria:Prior treatment with bendamustine-containing or fludarabine;Anti-T-cell monoclonal antibody, donor lymphocyte infusion, and CNS radiotherapy within 8 weeks; Chemotherapy, lenalidomide, bortezomib within 2 weeks; vincristine within 1 week; glucocorticoids (prednisone ≥7.5 mg/d or equivalent) within 72 h
* Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening), or any uncontrolled infection at screening
* Uncontrolled, symptomatic, intercurrent illness including but not limited to angina pectoris, cerebrovascular accident or transient ischemia (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), New York Heart Association (NYHA) classification of ≥ Class III congestive heart failure, severe arrhythmia poorly controlled by medications, hepatic, renal, or metabolic disorders, and hypertension that is uncontrolled by standard therapy；
* active bleeding, or venous thromboembolic event
* Autoimmune diseases (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, etc.) that result in end-organ damage or require systemic application of immunosuppressive drugs
* Central nervous system (CNS) disease or symptoms of CNS involvement
* Pregnant or nursing (lactating) women
* Presence of Grade 2 or above non-hematologic toxicity , alopecia and grade 2 neuropathy excluded
* Any Iinappropriate conditions in the opinion of the PI .

Primary outcomes:
measure: Incidence of Dose-limiting toxicity
timeFrame: Up to 28 days
measure: Incidence and severity of adverse events
timeFrame: Up to 15 years
Secondary outcomes:
measure: Overall response rate
timeFrame: up to 15 years
measure: Progression free survival
timeFrame: up to 15 years
measure: Overall survival
timeFrame: up to 15 years
measure: MRD negative response rates（ Acute Lymphoblastic Leukemia ）
timeFrame: up to 15 years
measure: Persistence of CD19/CD22 CAR-T cells blood, bone marrow
timeFrame: up to 15 years
Other outcomes:
Locations:
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University;
state: Jiangxi
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Rong Tao, MD
role: PRINCIPAL_INVESTIGATOR
References: