Clinical trial NCT05429905: Dual Anti-CD22/CD19 Chimeric Antigen Receptor-directed T Cells (CART2219.1) for Relapsed Refractory B-Lineage Leukaemia
Official title: Dual Anti-CD22/CD19 Chimeric Antigen Receptor-directed T Cells (CART2219.1) for Relapsed Refractory B-Lineage Leukaemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
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
Lead sponsor: KK Women's and Children's Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Singapore General Hospital
name: National University Hospital, Singapore
First posted: 2022-06-23
Enrollment: 48
Sex: ALL
Minimum age (years): 2
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Recommended Phase II Dose (Phase I, Cohort 1)
timeFrame: 30 days
measure: Number of patients with dose-limiting toxicities (Phase I, Cohort 1)
timeFrame: 30 days
measure: 12-month Leukaemia Free Survival (Phase II, Cohort 2 and 3)
timeFrame: 12 months
Secondary outcomes:
measure: Overall Survival Rate (OS)
timeFrame: 12 months
measure: Overall Response Rate (ORR)
timeFrame: 3 months
measure: Duration of Response (DOR)
timeFrame: Up to 24 months
measure: Duration of CAR-T persistence
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: KK Women's and Children's hospital
Study officials:
affiliation: KK Women's and Children's Hospital, BMTCT
name: Michaela Seng, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: KK Women's and Children's Hospital, BMTCT
name: Wing Hang Leung, MD PhD
role: STUDY_CHAIR
References: