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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoblastic Leukemia, in Relapse; B-cell Lymphoma Refractory; B-cell Lymphoma Recurrent; Acute Lymphoblastic Leukemia With Failed Remission
• Intervention / Treatment: Biological: KQ-2002 CAR-T cells （CD19/CD22 CAR T-Cells）

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.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Weijing Zhang; Phone Number: 88503 021-64175590; Email: JJYIN555@163.com

Study Locations

• China
  • Jiangxi
    • Nanchang, Jiangxi, China, 360000
      • Recruiting
      • The First Affiliated Hospital of Nanchang University;
      • Contact: Fei Li, MD; Phone Number: 13970038386; Email: lifeigcp@2022@163.com
      • Principal Investigator: Fei Li, MD
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Principal Investigator: Rong Tao, MD
      • Contact: Rong Tao, MD; Phone Number: 8621-64175590; Email: rtao@shca.org.cn
      • Contact: Wenhao Zhang, MD; Phone Number: 8621-64175590; Email: zwhl98@foxmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 .

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose expansion; CD19/CD22-CAR-transduced T cells at MTD or highest dose administered	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)
Experimental: Dose escalation; CD19/CD22-CAR-transduced T cells at escalating doses (0.5~5.0 ×10^6 cells/kg)	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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	Proportion of patients achieving a response	up to 15 years
Progression free survival	Preparative regimen until the documentation of disease progression or death due to any cause, whichever occurs first.	up to 15 years
Overall survival	Overall survival (OS) will be determined as the time from the start of the preparative regimen until death	up to 15 years
MRD negative response rates（ Acute Lymphoblastic Leukemia ）	MRD status post infusion，MRD will be performed utilizing flow cytometry or PCR.	up to 15 years
Persistence of CD19/CD22 CAR-T cells blood, bone marrow	pk properties of CD19/CD22 CAR-T	up to 15 years

Collaborators and Investigators

• Sponsor: Rong Tao
• Collaborators: Novatim Immune Therapeutics (Zhejiang) Co., Ltd.
• Investigators: Principal Investigator: Rong Tao, MD, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: June 1, 2024
• First Submitted That Met QC Criteria: June 1, 2024
• First Posted (Actual): June 6, 2024

Study Record Updates

• Last Update Posted (Actual): June 6, 2024
• Last Update Submitted That Met QC Criteria: June 1, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: CAR-T therapy
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Hematologic Diseases; Lymphoma; Lymphoma, B-Cell; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: KQ-2002-XC001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No