Lymphoblastic Leukemia, Acute, ChildhoodPhase 1NCT05043571
CARTALL: Chimeric-Antigen Receptor (CAR) T-Cell Therapy for Relapsed/ Refractory T-Lineage Acute Lymphoblastic Leukaemia
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 anti-CD7 CAR T-cells in patients with refractory or relapsed T-lineage acute lymphoblastic leukemia (T-ALL). Read more about this study
- Who is it for?
- Ages 6 months to 65 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
- 20 participants
- Where
- 1 siteSingapore
- Study dates
- 8 Sep 2021to 1 Nov 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis/ Disease define as:
- Relapsed T-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/ uL in CSF with morphological 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:
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- MRD = or > 1% by flow cytometry at the end of induction on day 33
- Or Failure to achieve morphological remission defined as > 5% blasts after standard induction chemotherapy
- Refractory disease as defined by:
- MRD = or > 0.01% by flow cytometry or molecular methods during 2 or more timepoints after induction therapy
- Minimum level of pulmonary reserve defined as Grade ≤ 1 dyspnoea and oxygen saturation (SpO2) of > 95% on room air
- Left ventricular systolic function (LVSF) ≥ 28% confirmed by echocardiogram, or left ventricular ejection fraction (LVEF) ≥ 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% CD7 expression on blast cells will be eligible for anti-CD7 PEBL-CAR-T cell infusion.
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 bone marrow failure states, such as Fanconi anaemia, Kostmann syndrome, Schwachman syndrome, or any other bone marrow 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 hepatitis C infections within 8 weeks of screening, or any uncontrolled infection at screening
- Positive Human Immunodeficiency Virus (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
- Central nervous system : Uncontrolled seizures or status epilepticus; increased intra-cranial pressure as evidenced by papilledema and CSF opening pressure > 20 cm water; decreased conscious state (any cause)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
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: Anti-CD7 Protein Expression Blocker (PEBL) Chimeric-Antigen Receptor (CAR) T-Cell Therapy for Relapsed/ Refractory T-Lineage Acute Lymphoblastic Leukaemia (CARTALL)
The objective of this study is to assess the safety and efficacy of anti-CD7 CAR T-cells in patients with refractory or relapsed T-lineage acute lymphoblastic leukemia (T-ALL).
Read the detailed description
A major obstacle to the development of effective CAR T-cells for T-cell malignancies is that the surface marker profile of malignant T-cells largely overlaps that of activated T lymphocytes. We developed a CAR T-cell approach that targets CD7, a T-cell marker highly expressed in all cases of T-cell ALL, including ETP-ALL. Its expression is also highly stable even in T-ALL cells exposed to chemotherapy. To prevent fratricide effect of the T cells, surface CD7 expression are effectively downregulated with the expression of an anti-CD7 Protein Expression Blocker (PEBL). Patients will receive anti-CD7 PEBL CART-cells. This will allow targeting the entire leukemia cell population to induce deeper and more durable remissions.
- 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
- T-ALL, CAR-T cell therapy, CAR T-cell therapy
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Precursor T-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 T-ALL, refractory or relapsed T-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) negativity at 1 month after Anti-CD7 PEBL 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 Anti-CD7 PEBL CAR T-cell infusion.
MRD levels will be determined by molecular based MRD by Ig/TCR. PCR and oncogene fusion transcript (OFT).
Measured: 30 days
Proportion of patient who shows CAR T-cell persistence 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 posted14 Sep 2021
- Study start8 Sep 2021 (estimated)
- Primary completion1 Nov 2026 (estimated)
- Study completion1 Nov 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.
- 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
- 20 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
- NCT05043571
- Sponsor's protocol ID
- 2020/01325
- Status last verified
- Jun 2021
- First submitted
- 13 Jun 2021
- Last updated
- 14 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 14 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anti-CD7 Protein Expression Blocker (PEBL) Chimeric-Antigen Receptor (CAR) T-Cell Therapy for Relapsed/ Refractory T-Lineage Acute Lymphoblastic Leukaemia (CARTALL)
- ClinicalTrials.gov ID
- NCT05043571
- Acronym / sponsor ID
- 2020/01325
- Conditions
- Lymphoblastic Leukemia, Acute, Childhood, Lymphoblastic Leukemia, Lymphoblastic Leukemia, Acute Adult, Lymphoblastic Leukemia in Children, CAR, CAR T-Cell-Related Encephalopathy Syndrome
- Keywords
- T-ALL, CAR-T cell therapy, CAR T-cell therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- 8 Sep 2021 (estimated)
- Primary completion
- 1 Nov 2026 (estimated)
- Study completion
- 1 Nov 2026 (estimated)
- First posted
- 14 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 anti-CD7 CAR T-cells in patients with refractory or relapsed T-lineage acute lymphoblastic leukemia (T-ALL).
Detailed description
A major obstacle to the development of effective CAR T-cells for T-cell malignancies is that the surface marker profile of malignant T-cells largely overlaps that of activated T lymphocytes. We developed a CAR T-cell approach that targets CD7, a T-cell marker highly expressed in all cases of T-cell ALL, including ETP-ALL. Its expression is also highly stable even in T-ALL cells exposed to chemotherapy. To prevent fratricide effect of the T cells, surface CD7 expression are effectively downregulated with the expression of an anti-CD7 Protein Expression Blocker (PEBL). Patients will receive anti-CD7 PEBL CART-cells. This will allow targeting the entire leukemia cell population to induce deeper and more durable remissions.
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 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (16 listed)
- 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/ uL in CSF with morphological 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 = or > 1% by flow cytometry at the end of induction on day 33
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 bone marrow failure states, such as Fanconi anaemia, Kostmann syndrome, Schwachman syndrome, or any other bone marrow 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 hepatitis C infections 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 T-ALL, refractory or relapsed T-ALL. | Biological | Single arm |
Primary outcome
Proportion of participant who are flow cytometry minimal residual disease (MRD) negativity at 1 month after Anti-CD7 PEBL 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 Anti-CD7 PEBL CAR T-cell infusion.
Time frame: 30 days
Proportion of patient who shows CAR T-cell persistence 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
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 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.
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 16 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: looking for participants now, as of the sponsor's last update on 14 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?
This study is still under way. Results are not available in the source record yet.
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) negativity at 1 month after Anti-CD7 PEBL 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 14 Sep 2021.