Lymphoblastic Leukemia, Acute, ChildhoodPhase 1ALaCARTNCT05038696
ALaCART-B: Acute Leukemia and Chimeric Antigen Receptor-T Cell Therapy for B-lymphoblastic Leukemia.
A Phase 1 study testing CAR T-cell therapy in people with Lymphoblastic Leukemia, Acute, Childhood and Lymphoblastic Leukemia, run by National University Hospital, Singapore at 1 site in Singapore.
Trial summary
The objective of this study is to assess the safety and efficacy of a immunophenotype-adapted approach using CAR T-cells in patients with high-risk, refractory or relapsed B-lineage acute lymphoblastic leukemia (B-ALL). Read more about this study
- Who is it for?
- Ages 6 months to 80 years
- Conditions the study is for
- Lymphoblastic Leukemia, Acute, Childhood, Lymphoblastic Leukemia, Lymphoblastic Leukemia, Acute Adult
- What is being tested?
- CAR T-cell therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteSingapore
- Study dates
- 28 Apr 2021to 1 Aug 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Fulfil the Diagnosis/ Disease define as:
- Relapsed B-cell acute lymphoblastic leukaemia/ lymphoma as defined by:
- Bone marrow disease = or > 0.01% by MRD as determined by flow cytometry Or CNS disease as defined as > 5 WBCs in CSF by morphology, or flow cytometric or molecular evidence of blasts or biopsy proven recurrence in the eye or brain.
- Or Extramedullary relapse as defined by morphological evidence of blasts in the testis or any other extramedullary sites
- Induction failure as defined by Day 33/ End of induction:
- MRD ≥ 1% by flow cytometry on the Ma-Spore ALL 2020 protocol Or Failure to achieve morphological remission defined as > 5% blasts after standard induction chemotherapy
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- Refractory disease as defined by:
- MRD ≥ 0.01% by flow cytometry or molecular methods during 2 or more timepoints after induction therapy
- Any high risk features including :
- BCR-ABL1, BCR-ABL1-like, - ABL1-r, PDGFRB-r, TCF3-HLF, MLL-r, hypodiploid ALL (< 45 chromosomes), p53 pathogenic mutation as defined by RNA Seq or other molecular methods.
- Patients who are unable to tolerate standard chemotherapy due to significant toxicity as well as other comorbidities
- Minimum level of pulmonary reserve defined as grade ≤ 1 dyspnoea and oxygen saturation of > 95% on room air
- Left ventricular systolic function ≥ 28% confirmed by echocardiogram, or left ventricular ejection fraction ≥ 45% confirmed by echocardiogram within 3 months of screening
- Karnofsky (age ≥ 16 years) or Lansky (age < 16 years) performance status ≥ 50 at screening
- Normal Age-adjusted eGFR Creatinine Clearance within 3 months of screening
- Alanine aminotransferase ≤ 5 times the upper limit of normal for age
- Patients with > 99.9% of CD19 expression on blast cells will be eligible for anti-CD19 CAR T-cell infusion.
- Patients with partial or absent CD19 expression (< 99.9%) on blast cells will be eligible to receive combinations of other CAR T-cells depending on the pattern of antigen expression.
Who cannot join
- Failure to meet any of the inclusion criteria.
- Patients who test positive on urine pregnancy testing and are pregnant or are lactating
- Concomitant genetic syndromes associated with BM failure states, such as Fanconi anaemia, Kostmann syndrome, Schwachman syndrome, or any other BM failure syndrome with the exception of Down syndrome
- Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and no evidence of active disease
- Active or latent hepatitis B or active hepatitis C within 8 weeks of screening, or any uncontrolled infection at screening
- Positive HIV test within 8 weeks of screening
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- Grade 2 to 4 acute graft-vs-host disease (GVHD) or extensive chronic GVHD
- Received an investigational medicinal product within 30 days of screening
- Persistent disease or relapse after other forms of CAR-T cell therapy.
Trial locations and contacts
1 site in 1 country.
Singapore1 site, 1 recruiting
- Recruiting
Allen Yeoh Eng Juh
Singapore, 119228
Allen Yeoh, M.D, (+65) 6772 2002, paeyej@nus.edu.sg
Zhiwei Chen, BSc., (+65) 6772 4406, chen.zhiwei@nus.edu.sg
About this study
Official title: Chimeric-Antigen Receptor (CAR) T-Cell Therapy Using Multiple CARs and Cell Marker Profiling in High Risk and Relapsed/ Refractory B-Lineage Acute Lymphoblastic Leukaemia
The objective of this study is to assess the safety and efficacy of a immunophenotype-adapted approach using CAR T-cells in patients with high-risk, refractory or relapsed B-lineage acute lymphoblastic leukemia (B-ALL).
Read the detailed description
Patients will receive CART-cells with one or more specificities according to the phenotypic profile of the leukemic cells in each individual patient. This will allow targeting the entire leukemia cell population to induce deeper and more durable remissions. Although it would be possible to administer CART-cells targeting all possible antigens to all patients, this indiscriminate approach would increase the CAR T-cell dose and hence, the risk of toxicity in patients that could be effectively treated with a lower, less toxic, CAR T-cell dose. Moreover, the cost of the procedure increases proportionally with the number of CAR T-cells used, limiting our capacity to enrol other patients. Reducing the number of CART-cells below the dose that we set, will inevitably increase the risk of treatment failure, according to the literature and our own experience.
- Conditions
- Lymphoblastic Leukemia, Acute, Childhood, Lymphoblastic Leukemia, Lymphoblastic Leukemia, Acute Adult, Lymphoblastic Leukemia in Children, CAR, CAR T-Cell-Related Encephalopathy Syndrome
- Being tested
- CAR T-cell therapy
- Keywords
- B-ALL, CAR-T cell therapy, CAR T-cell therapy
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAR T-cell therapyBiological
This is a single-centre, phase I study to determine the efficacy and safety of CAR T-cell therapy in patients with high-risk B-ALL, refractory or relapsed B-ALL.
| Study group | Role | What they receive |
|---|---|---|
| Single arm | Experimental | Single arm Phase I Clinical Trial Receives: Biological: CAR T-cell therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of participant who are flow cytometry minimal residual disease (MRD) negative at the end of 1 month after CAR T-cell infusion.
MRD levels will be determined by flow cytometry, The target sensitivity of flow MRD is <0.01% when available.
Measured: 30 days
Secondary outcomes (2)
Proportion of participant who are minimal residual disease (MRD) negative with molecular base assay at the end of 1 month after CAR T-cell infusion.
MRD levels will be determined by molecular based MRD. PCR and oncogene fusion transcript (OFT).
Measured: 30 days
Proportion of patient who shows CAR T-cell persistence and presence of B-cell aplasia by immunophenotyping using flow cytometry in bone marrow, peripheral blood and CSF samples at multiple study time points following CAR T cell infusion
Flow cytometry will be performed on bone marrow, peripheral blood and CSF samples at multiple study time points following CAR T cell infusion
Measured: 1 month to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2021
- Study start28 Apr 2021
- Primary completion1 May 2026 (estimated)
- Study completion1 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lymphoblastic Leukemia, Acute, ChildhoodStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Allen Yeoh, M.D, Principal investigator, National University Hospital, SingaporeDario Campana, M.D, PhD, Study director, National University of Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05038696
- Sponsor's protocol ID
- 2020/00865
- Acronym
- ALaCART
- Status last verified
- Apr 2021
- First submitted
- 26 May 2021
- Last updated
- 9 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chimeric-Antigen Receptor (CAR) T-Cell Therapy Using Multiple CARs and Cell Marker Profiling in High Risk and Relapsed/ Refractory B-Lineage Acute Lymphoblastic Leukaemia
- ClinicalTrials.gov ID
- NCT05038696
- Acronym / sponsor ID
- ALaCART / 2020/00865
- Conditions
- Lymphoblastic Leukemia, Acute, Childhood, Lymphoblastic Leukemia, Lymphoblastic Leukemia, Acute Adult, Lymphoblastic Leukemia in Children, CAR, CAR T-Cell-Related Encephalopathy Syndrome
- Keywords
- B-ALL, CAR-T cell therapy, CAR T-cell therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- 28 Apr 2021 (actual)
- Primary completion
- 1 May 2026 (estimated)
- Study completion
- 1 Aug 2026 (estimated)
- First posted
- 9 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to assess the safety and efficacy of a immunophenotype-adapted approach using CAR T-cells in patients with high-risk, refractory or relapsed B-lineage acute lymphoblastic leukemia (B-ALL).
Detailed description
Patients will receive CART-cells with one or more specificities according to the phenotypic profile of the leukemic cells in each individual patient. This will allow targeting the entire leukemia cell population to induce deeper and more durable remissions. Although it would be possible to administer CART-cells targeting all possible antigens to all patients, this indiscriminate approach would increase the CAR T-cell dose and hence, the risk of toxicity in patients that could be effectively treated with a lower, less toxic, CAR T-cell dose. Moreover, the cost of the procedure increases proportionally with the number of CAR T-cells used, limiting our capacity to enrol other patients. Reducing the number of CART-cells below the dose that we set, will inevitably increase the risk of treatment failure, according to the literature and our own experience.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm | Experimental | Biological: CAR T-cell therapySingle arm Phase I Clinical Trial |
Who may qualify
- Ages
- 6 months to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (18 listed)
- Fulfil the Diagnosis/ Disease define as:
- Bone marrow disease = or > 0.01% by MRD as determined by flow cytometry Or CNS disease as defined as > 5 WBCs in CSF by morphology, or flow cytometric or molecular evidence of blasts or biopsy proven recurrence in the eye or brain.
- Or Extramedullary relapse as defined by morphological evidence of blasts in the testis or any other extramedullary sites
- MRD ≥ 1% by flow cytometry on the Ma-Spore ALL 2020 protocol Or Failure to achieve morphological remission defined as > 5% blasts after standard induction chemotherapy
- MRD ≥ 0.01% by flow cytometry or molecular methods during 2 or more timepoints after induction therapy
Key exclusion criteria (9 listed)
- Failure to meet any of the inclusion criteria.
- Patients who test positive on urine pregnancy testing and are pregnant or are lactating
- Concomitant genetic syndromes associated with BM failure states, such as Fanconi anaemia, Kostmann syndrome, Schwachman syndrome, or any other BM failure syndrome with the exception of Down syndrome
- Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and no evidence of active disease
- Active or latent hepatitis B or active hepatitis C within 8 weeks of screening, or any uncontrolled infection at screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CAR T-cell therapyThis is a single-centre, phase I study to determine the efficacy and safety of CAR T-cell therapy in patients with high-risk B-ALL, refractory or relapsed B-ALL. | Biological | Single arm |
Primary outcome
Proportion of participant who are flow cytometry minimal residual disease (MRD) negative at the end of 1 month after CAR T-cell infusion.
Time frame: 30 days
MRD levels will be determined by flow cytometry, The target sensitivity of flow MRD is <0.01% when available.
2 secondary outcomes
Proportion of participant who are minimal residual disease (MRD) negative with molecular base assay at the end of 1 month after CAR T-cell infusion.
Time frame: 30 days
Proportion of patient who shows CAR T-cell persistence and presence of B-cell aplasia by immunophenotyping using flow cytometry in bone marrow, peripheral blood and CSF samples at multiple study time points following CAR T cell infusion
Time frame: 1 month to 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Allen Yeoh, M.D principal investigator
National University Hospital, Singapore
Dario Campana, M.D, PhD study director
National University of Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CAR T-cell therapy in people with Lymphoblastic Leukemia, Acute, Childhood and Lymphoblastic Leukemia, run by National University Hospital, Singapore at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Allen Yeoh, M.D (+65 6772 2002, paeyej@nus.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participant who are flow cytometry minimal residual disease (MRD) negative at the end of 1 month after CAR T-cell infusion. (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2021.