Interleukin-2 Following 4SCAR19/22 T Cells Targeting Refractory and/or Recurrent B Cell Malignancies

NCT03098355 | Withdrawn Phase 1 DMC

• 1 other identifier: anti-CD19/22 CART Cells
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Clinical studies of CD19 CAR-T cells in the treatment of blood and lymphatic system tumors have achieved unprecedented successes. Because of the heterogeneity of the tumor, patients often carry CD19-negative tumor cell clones that express alternative target antigens (such as CD22, CD20 and CD123). In order to effectively eradicate all tumor clones and prevent recurrence, alternative tumor antigens besides CD19 are considered for CAR-T cell targeting. In this tudy, autologous T cells are genetically modified with 4th generation anti-CD19 and anti-CD22 CARs (4SCAR19/22) using lentiviral vectors. For safety consideration, the 4SCAR is engineered with an inducible caspase 9 self-withdrawal genetic design that allows for rapid elimination of the infused CAR-T cells. Interleukin-2 has been shown to boost immune response against leukemia cells. The serum interleukin-6 level will be monitored and when it returns to normal range by day 28 after CAR-T cell infusion, patients will receive subcutaneous injection of interleukin-2, and evaluated for 24 months for safety, efficacy and persistence of CAR T cells.

Conditions

B-Cell Leukemia; B-Cell Lymphoma

Keywords

CART; CD19; CD22; Interleukin-2

Outcome Measures

Primary Outcomes (1)

• Evaluate the frequency and severity of adverse events including, but not limited to, cytokine release syndrome (CRS)

  b)Evaluate grade 3 and higher toxicity rate of patients (toxicity possibly attributed to 4SCAR19/22 T cells)

  From date of dosing ( day 1 ) up to 50 weeks

Study Arms (1)

4SCAR19/22 T cells and interleukin-2

EXPERIMENTAL

Patients with resistant or refractory B cell acute lymphoblastic leukemia (ALL) or non-hodgkin's lymphoma (NHL) will receive CAR-T cells at a total dose of 0.5-5x10\^6/kg and regular subcutaneous injection of interleukin-2 every other day for 2 weeks and then rest for 2 weeks for up to 6 months after their serum interleukin-6 levels returned to normal range from day 28 after CAR-T cell infusion.

Biological: 4SCAR19/22 T cells; Drug: Interleukin-2

Interventions

4SCAR19/22 T cells BIOLOGICAL

CD19/CD22-targeted 4th Generation CAR-T Cell (4SCAR19/22)

4SCAR19/22 T cells and interleukin-2

Interleukin-2 DRUG

Interleukin-2 of 250,000iu/m\^2 every other day for 2 weeks and then rest for 2 weeks for up to 6 months.

Also known as: IL-2

4SCAR19/22 T cells and interleukin-2

Eligibility Criteria

• Age: 1 Year - 14 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Relapsed or refractory CD19+ B-cell lymphoma or leukemia.
• Measurable disease.
• Karnofsky/jansky score of 60% or greater.
• ≥1 years old and ≤14 years.
• Fertile females/males.
• Expected survival\>12 weeks.
• Histologically confirmed as CD19/20-positive ALL/NHL and who meet one of the following conditions:
• Patients receive at least 2-4 prior combination chemotherapy regimens (not including single agent monoclonal antibody therapy) and fail to achieve CR.
• Recurrent disease and not eligible for allogeneic stem cell transplantation, and stable disease after therapy but refused further treatment.
• Disease recurrence after stem cell transplantation.
• Diagnosis as lymphoma, and refuse conventional treatment such as chemotherapy, radiation, stem cell transplantation and monoclonal antibody therapy.
• Creatinine \< 2.5 mg/dl.
• Alanine transaminase (ALT) \<3x upper limit of normal (ULN), aspartate aminotransferase (AST) \<3x ULN.
• Bilirubin \< 2.0 mg/dl.
• Adequate venous access for apheresis, and no other contraindications for leukapheresis.

You may not qualify if:

• A history of mental illness and poorly controlled.
• Patients with symptoms of central nervous system.
• Suffering severe cardiovascular or respiratory disease.
• Accompanied by other malignant tumor.
• Known human immunodeficiency virus (HIV) infection.
• Active and/or severe infection (e.g. tuberculosis, sepsis and opportunistic infections, active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection).
• Other serious underlying medical conditions, which, in the Investigator's judgment, could impair the ability of the patient.
• Taking immunosuppressive agents within 1 week due to organ transplantation or other disease which need long-lasting administration.
• Patients that do not consent to tissue and blood sample collection and storage in a biobank.
• Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed 48 hours before infusion.
• Pregnancy and nursing females.

Sponsors & Collaborators

• Zhujiang Hospital: lead
• Shenzhen Geno-Immune Medical Institute: collaborator

Study Sites (1)

Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, 510282, China

Location

MeSH Terms

Conditions

Leukemia, B-Cell; Lymphoma, B-Cell

Interventions

Interleukin-2

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Li-hua Yang, Ph.D.

  Southern Medical University, China

  PRINCIPAL INVESTIGATOR

• Lung-Ji Chang, Ph.D.

  Shenzhen Geno-Immune Medical Institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2017
• First Posted: March 31, 2017
• Study Start: December 30, 2017
• Primary Completion: December 15, 2022
• Study Completion: December 31, 2023
• Last Updated: March 18, 2024

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)