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

NCT05429905 | Unknown Phase 1 DMC

• 1 other identifier: CART2219-1.0
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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

Keywords

CAR T-cell therapy; B-ALL; Relapsed/ Refractory

Outcome Measures

Primary Outcomes (3)

• Recommended Phase II Dose (Phase I, Cohort 1)

  The RP2D will be the dose level at which \< 1 DLT in 3 patients or \< 2 DLT in 6 patients is observed in both the adult and paediatric dose escalation stratas.

  30 days

• Number of patients with dose-limiting toxicities (Phase I, Cohort 1)

  To be DLTs, adverse events must be suspected to be secondary to CAR-T cell infusion, occur during the first 30 days after infusion and meet at least one of the following criteria: 1. Grade ≥ 3 non-hematologic toxicities, with the following exceptions: * Laboratory abnormalities without associated symptomatology or clinical consequence that resolve in less than 7 days; * Grade ≤ 2 cytokine release syndrome; * Grade 3 cytokine release syndrome that improves to grade ≤ 2 within 3 days of intervention; * Grade 3 neurotoxicity that resolves to grade 2 or less within 3 days. * Laboratory abnormalities compatible with tumor lysis syndrome; 2. Grade ≥ 4 hematologic toxicities that persist at a grade ≥ 3 for \>21 days. Cytokine release syndrome and immune-effector cell associated neurotoxicity syndrome (ICANS) are graded according to ASTCT consensus grading. Adverse events are graded according to CTCAE version 5.0.

  30 days

• 12-month Leukaemia Free Survival (Phase II, Cohort 2 and 3)

  Survival with Marrow MRD \<0.01% by flow cytometry

  12 months

Secondary Outcomes (4)

• Overall Survival Rate (OS)

  12 months

• Overall Response Rate (ORR)

  3 months

• Duration of Response (DOR)

  Up to 24 months

• Duration of CAR-T persistence

  Up to 24 months

Study Arms (3)

Cohort 1 (Dose-escalation)

EXPERIMENTAL

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

Biological: Phase I

Cohort 2 (High MRD)

EXPERIMENTAL

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

Biological: Phase II

Cohort 3 (Extramedullary ALL)

EXPERIMENTAL

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

Biological: Phase II

Interventions

Phase I 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 1 (Dose-escalation)

Phase II BIOLOGICAL

RP2D will be determined in Phase I

Cohort 2 (High MRD); Cohort 3 (Extramedullary ALL)

Eligibility Criteria

• Age: 2 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• KK Women's and Children's Hospital: lead
• Singapore General Hospital: collaborator
• National University Hospital, Singapore: collaborator

Study Sites (1)

KK Women's and Children's hospital

Singapore, Singapore

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic

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

Intervention Hierarchy (Ancestors)

Clinical Trials as Topic; Clinical Studies as Topic; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Michaela Seng, MD

  KK Women's and Children's Hospital, BMTCT

  PRINCIPAL INVESTIGATOR

• Wing Hang Leung, MD PhD

  KK Women's and Children's Hospital, BMTCT

  STUDY CHAIR

Central Study Contacts

Michaela Seng, MD

CONTACT

+65 6394 1989; michaela.seng@singhealth.com.sg

Germaine Liew, BS

CONTACT

63945025; germaine.liew.shimin@singhealth.com.sg

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Phase 1 run-in will be conducted to determine the recommended phase II dose(s) (RP2D) for adult and paediatric patients in independent dose escalation cohorts. Phase II will enrol patients in 2 concurrent cohorts at the R2PD.

Study Record Dates

• First Submitted: December 16, 2021
• First Posted: June 23, 2022
• Study Start: July 18, 2022
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2025
• Last Updated: March 9, 2023

Record last verified: 2023-03

Locations

SG (1)