- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05429905
Dual Anti-CD22/CD19 Chimeric Antigen Receptor-directed T Cells (CART2219.1) for Relapsed Refractory B-Lineage Leukaemia
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Michaela Seng, MD
- Phone Number: +65 6394 1989
- Email: michaela.seng@singhealth.com.sg
Study Contact Backup
- Name: Germaine Liew, BS
- Phone Number: 63945025
- Email: germaine.liew.shimin@singhealth.com.sg
Study Locations
-
-
-
Singapore, Singapore
- Recruiting
- KK Women's and Children's Hospital
-
Contact:
- Michaela Seng
- Phone Number: +65 6394 1989
- Email: michaela.seng@singhealth.com.sg
-
Principal Investigator:
- Michaela Seng
-
Principal Investigator:
- Francesca Lorraine Lim Wei Inng
-
Principal Investigator:
- Liang Piu Koh
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
Dose-escalations for adults and paediatrics will be performed in 2 independent strata for determination of RP2D. |
Experimental: Cohort 2 (High MRD)
Patients with B-ALL with high MRD after induction therapy or after consolidation therapy in replacement of stem cell transplant
|
RP2D will be determined in Phase I
|
Experimental: Cohort 3 (Extramedullary ALL)
Patients with testicular or central nervous system B-ALL in replacement of radiation
|
RP2D will be determined in Phase I
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Recommended Phase II Dose (Phase I, Cohort 1)
Time Frame: 30 days
|
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)
Time Frame: 30 days
|
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:
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)
Time Frame: 12 months
|
Survival with Marrow MRD <0.01%
by flow cytometry
|
12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival Rate (OS)
Time Frame: 12 months
|
Percentage of patients in the study who are alive 12 months after CAR-T infusion.
|
12 months
|
Overall Response Rate (ORR)
Time Frame: 3 months
|
Percentage of patients in the study who have a partial or complete response to the treatment within 3 months.
|
3 months
|
Duration of Response (DOR)
Time Frame: Up to 24 months
|
Duration of complete remission (CR or CR with partial/incomplete haematological recovery)
|
Up to 24 months
|
Duration of CAR-T persistence
Time Frame: Up to 24 months
|
Duration of measurable CAR-T above detection limits in peripheral blood and/or marrow
|
Up to 24 months
|
Collaborators and Investigators
Investigators
- Principal Investigator: Michaela Seng, MD, KK Women's and Children's Hospital, BMTCT
- Study Chair: Wing Hang Leung, MD PhD, KK Women's and Children's Hospital, BMTCT
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CART2219-1.0
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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