CD19/CD22 CAR-T Cells in Adults With R/R ALL or NHL

Acute Lymphoblastic Leukemia, in Relapse Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06445803
• Other study ID #: KQ-2002-XC001
• Status: Recruiting
• Phase: Phase 1
• Start date: May 31, 2024
• Est. completion date: December 2026

Study information

• Verified date: June 2024
• Source: Fudan University
• Contact: Weijing Zhang
• Phone: 021-64175590
• Email: JJYIN555[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: December 2026
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 .

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia With Failed Remission
• Acute Lymphoblastic Leukemia, in Relapse
• B-cell Lymphoma Recurrent
• B-cell Lymphoma Refractory
• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• KQ-2002 CAR-T cells (CD19/CD22 CAR T-Cells)
CD19/CD22 cells will be infused on Day1 after induction chemotherapy regimen. Lymphodepleting chemotherapy:3 days of IV chemotherapy with fludarabine and cyclophosphamide. Fludarabine 30 mg/m2/day IV x 4 days (days -5 through -3) Cyclophosphamide 500 mg/m2/day IV x 2 days (days -5 and-3)

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Nanchang University;	Nanchang	Jiangxi
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Rong Tao	Novatim Immune Therapeutics (Zhejiang) Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Dose-limiting toxicity	Will be recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	Up to 28 days
Primary	Incidence and severity of adverse events	Will be recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	Up to 15 years
Secondary	Overall response rate	Proportion of patients achieving a response	up to 15 years
Secondary	Progression free survival	Preparative regimen until the documentation of disease progression or death due to any cause, whichever occurs first.	up to 15 years
Secondary	Overall survival	Overall survival (OS) will be determined as the time from the start of the preparative regimen until death	up to 15 years
Secondary	MRD negative response rates( Acute Lymphoblastic Leukemia )	MRD status post infusion,MRD will be performed utilizing flow cytometry or PCR.	up to 15 years
Secondary	Persistence of CD19/CD22 CAR-T cells blood, bone marrow	pk properties of CD19/CD22 CAR-T	up to 15 years