Dual Anti-CD22/CD19 Chimeric Antigen Receptor-directed T Cells (CART2219.1) for Relapsed Refractory B-Lineage Leukaemia

NCT ID: NCT05429905

Last Updated: 2023-03-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-18
• Study Completion Date: 2025-12-31

Brief Summary

The purpose of this study is to deliver dual-targeting CAR-T cell therapy (CART 2219.1) as a salvage treatment to patients with relapsed/refractory B-lineage leukaemia in place of stem cell transplant or irradiation.

Conditions

Lymphoblastic Leukemia; Lymphoblastic Leukemia, Acute, Childhood; Lymphoblastic Leukemia in Children; Lymphoblastic Leukemia, Acute Adult; CAR

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1 (Dose-escalation)

Dose-finding and dose expansion cohort for intravenous autologous anti-CD22/CD19 CAR-T using a relapsed refractory B-ALL cohort.

Group Type: EXPERIMENTAL

Phase I

Intervention Type: BIOLOGICAL

• Dose level 0: CAR+CD3+ 0.4 x 10e6/kg (de-escalation dose)
• Dose level 1: CAR+CD3+ 1 x 10e6/kg (starting dose)
• Dose level 2: CAR+CD3+ 2.5 x 10e6/kg.

Dose-escalations for adults and paediatrics will be performed in 2 independent strata for determination of RP2D.

Cohort 2 (High MRD)

Patients with B-ALL with high MRD after induction therapy or after consolidation therapy in replacement of stem cell transplant

Group Type: EXPERIMENTAL

Phase II

Intervention Type: BIOLOGICAL

RP2D will be determined in Phase I

Cohort 3 (Extramedullary ALL)

Patients with testicular or central nervous system B-ALL in replacement of radiation

Group Type: EXPERIMENTAL

Phase II

Intervention Type: BIOLOGICAL

RP2D will be determined in Phase I

Interventions

Phase I

• Dose level 0: CAR+CD3+ 0.4 x 10e6/kg (de-escalation dose)
• Dose level 1: CAR+CD3+ 1 x 10e6/kg (starting dose)
• Dose level 2: CAR+CD3+ 2.5 x 10e6/kg.

Dose-escalations for adults and paediatrics will be performed in 2 independent strata for determination of RP2D.

Intervention Type: BIOLOGICAL

Phase II

RP2D will be determined in Phase I

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

All Cohorts:

• Age 2 to 75 years
• Absolute blood CD3+ T cell count ≥100/μl
• ECOG performance score of ≤2 if >16 years old, or Lansky performance score of >50 if ≤16 years old at screening
• Patients and/or parents must give their written informed consent/assent.
• Patients have relapsed/refractory B-lineage acute lymphoblastic leukaemia, includes persistent minimal residual disease (MRD)

Cohort 1 (Phase I): Relapsed/Refractory B-ALL

• Patients must have relapsed/refractory (r/r) B-lineage ALL meeting one of the following disease-specific criteria:

• Patients with r/r ALL with >5% blasts in BM (M2 or M3) after at least one standard chemotherapy and one salvage regimen who are ineligible for allogeneic stem cell transplant (alloSCT) or have refractory disease activity (e.g. persistent MRD in bone marrow) precluding alloSCT, or
• Patients with Ph+ ALL if they are intolerant to tyrosine kinase inhibitor (TKI) therapy, or if they have r/r disease after treatment including TKI, or
• Patients who have relapsed post-allogeneic HSCT and are at least 100 days post-transplant, with no evidence of active GVHD, > 6 weeks post donor lymphocyte infusion (DLI) and no longer taking immunosuppressive agents for at least 30 days prior to enrolment.
• Patients who have relapsed after prior CAR-T therapy who are not eligible for stem cell transplant and have < 5% circulating CAR-T prior to apheresis
• Patients with refractory/relapsed combined extramedullary ALL are eligible. This includes patients with combined CNS-2 (<5 WBC/μl CSF, with blasts on cytospin) or CNS-3 (>5 WBC/ul CSF, with blasts on cytospin) disease and patients with combined testicular relapse.

Cohort 2 (Phase II): B-ALL with persistent MRD (High Risk B-ALL)

• Patients must have persistent MRD >0.1% blasts after frontline induction chemotherapy or >0.01% blasts after consolidation therapy.

Cohort 3 (Phase II): Relapsed/Refractory Extramedullary B-ALL

• Patients with testicular leukaemia confirmed on biopsy
• Patients with CNS-3 B-ALL or Leptomeningeal disease
• Patients with combined bone marrow and extramedullary relapse (as defined in Cohort 1) are eligible.

Exclusion Criteria

All Cohorts:

• Blasts are negative for both CD22 and CD19 on flow cytometry or immunohistochemistry, defined as < 10% of blasts staining positive for CD22 and CD19 respectively [IBFM 2016 Consensus Guidelines].
• Current autoimmune disease, or history of autoimmune disease with potential CNS involvement
• Active clinically significant CNS dysfunction (including but not limited to uncontrolled seizure disorders, cerebrovascular ischemia or hemorrhage, dementia, paralysis)
• History of an additional malignancy other than non-melanoma skin cancer or carcinoma in situ unless disease free for ≥3 years.
• Pulmonary function: Patients with pre-existing severe lung disease (FEV1 or FVC < 65%) or an oxygen requirement of >28% O2 supplementation or active pulmonary infiltrates on chest X-ray at the time scheduled for T cell infusion
• Cardiac function: Fractional shortening <28% or left ventricular ejection fraction <50% by echocardiography
• Renal function: Creatinine clearance <50 mL/min/1.73 m2
• Liver function: Patients with a serum bilirubin >3 times upper limit of normal or an AST or ALT > 5 times upper limit of normal, unless due to leukemic liver infiltration in the estimation of the investigator
• Rapidly progressive disease that in the estimation of the investigator would compromise ability to complete study therapy
• Active Hepatitis B (HBsAg positive) or Hepatitis C (PCR positive), or known infection with human immunodeficiency virus (HIV)
• Pregnant or nursing (lactating) women
• In relation to prior therapy:

• Use of immunotherapy, cell-based or other investigational treatment within 30 days of CAR-T infusion

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Singapore General Hospital

OTHER

Sponsor Role: collaborator

National University Hospital, Singapore

OTHER

Sponsor Role: collaborator

KK Women's and Children's Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michaela Seng, MD

Role: PRINCIPAL_INVESTIGATOR

KK Women's and Children's Hospital, BMTCT

Wing Hang Leung, MD PhD

Role: STUDY_CHAIR

KK Women's and Children's Hospital, BMTCT

Locations

KK Women's and Children's hospital

Singapore, , Singapore

Site Status: RECRUITING

Countries

Singapore

Central Contacts

Michaela Seng, MD

Role: CONTACT

michaela.seng@singhealth.com.sg

+65 6394 1989

Germaine Liew, BS

Role: CONTACT

germaine.liew.shimin@singhealth.com.sg

63945025

Facility Contacts

Michaela Seng

Role: primary

michaela.seng@singhealth.com.sg

+65 6394 1989

Other Identifiers

CART2219-1.0

Identifier Type: -

Identifier Source: org_study_id