Acute Lymphoblastic LeukemiaEarly Phase 1NCT04532203
A Study of CAR-T Cells Therapy for Patients With Relapsed and/or Refractory Central Nervous System Hematological Malignancies
A Early Phase 1 study testing CAR-T cells and Ommaya Reservoir in people with Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma, run by Zhejiang University at 1 site in China.
Trial summary
A Study of CAR-T Cells Therapy for Patients With Relapsed and/or Refractory Central Nervous System Hematological Malignancies Read more about this study
- Who is it for?
- Ages 3 to 75 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Non-Hodgkin's Lymphoma
- What is being tested?
- CAR-T cells and Ommaya Reservoir
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2020to 1 Nov 2026
- Phase
- Early 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 3 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female aged 3-70 years;
- Histologically confirmed diagnosis of B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1);
- Relapsed or refractory CD19+ B-ALL (meeting one of the followingconditions):
- CR not achieved after standardized chemotherapy;
- CR achieved following the first induction, but CR duration isless than 12 months;
- Ineffectively after first or multiple remedial treatments;
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- 2 or more relapses;
- The number of primordial cells (lymphoblast and prolymphocyte)in bone marrow is>5% (by morphology), and/or >1% (by flowcytometry);
- Philadelphia-chromosome-negative (Ph-) patients; or Philadelphia-chromosome-positive (Ph+) patients who cannot tolerate TKI treatments or do not respond to 2 TKI treatments;
- Male or female aged 18-75 years;
- Histologically confirmed diagnosis of DLBCL (NOS), FL, DLBCL transformed from CLL/SLL, PMBCL, and HGBCL per the WHOClassification Criteria for Lymphoma (2016);
- Relapsed or refractory B-NHL (meeting one of the followingconditions):
- No response or relapse after second-line or abovechemotherapy regimens;
- Primary drug resistance;
- Relapse after auto-HSCT;
- At least one assessable tumor lesion per Lugano 2014 criteria;
- Common inclusion criteria for B-ALL and B-NHL:
- Highly suspected or confirmed central nervous system involvement of hematological malignancies;
- Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal, creatinine ≤ 176.8 umol/L;
- Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;
- No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;
- Estimated survival time ≥ 3 months;
- ECOG performance status 0 to 2;
- Patients or their legal guardians volunteer to participate in the study and sign the informed consent.
Who cannot join
- Subjects with any of the following exclusion criteria were not eligible for this trial:
- History of craniocerebral trauma, conscious disturbance,epilepsy,cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;
- Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
- Pregnant (or lactating) women;
- Patients with severe active infections (excluding simple urinarytractinfectionand bacterial pharyngitis);
- Active infection of hepatitis B virus or hepatitis C virus;
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- Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving inhaled steroids;
- Previously treated with any CAR-T cell product or other genetically-modified T cell therapies;
- Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts,orbilirubin>2.0 mg/dl;
- Other uncontrolled diseases that were not suitable for this trial;
- Patients with HIV infection;
- Any situations that the investigator believes may increase the risk ofpatients or interfere with the results of study.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
The First Affiliated Hospital，College of Medicine, Zhejiang University
Hangzhou, Zhejiang, 310003
He Huang, PhD, 86-13605714822, hehuangyu@126.com
About this study
Official title: Clinical Trial for the Safety and Efficacy of CAR-T Cells Therapy for Patients With the Central Nervous System Involvement of Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia or B-cell Non-Hodgkin's Lymphoma
A Study of CAR-T Cells Therapy for Patients With Relapsed and/or Refractory Central Nervous System Hematological Malignancies
Read the detailed description
This is a single arm, open-label, single-center study. This study is indicated for relapsed or refractory central nervous system CD19+ B-cell hematological malignancies, including acute lymphoblastic leukemia and B-cell non-Hodgkin's lymphoma. The selections of dose levels and the numberof subjects are based on clinical trialsof similar foreign products. Two groups of patients will be enrolled, 36 in eachgroup. Primary objective is to explore the safety, main consideration is dose-related safety.
- Being tested
- CAR-T cells, Ommaya Reservoir
- Keywords
- Acute Lymphoblastic Leukemia, Non-Hodgkin's Lymphoma, CAR T-cell therapy
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAR-T cellsDrug
Also called CAR-T cells injection
Each subject receive CAR T-cells by intravenous infusion
Ommaya ReservoirProcedure or surgery
Surgical catheter placement into the fourth ventricle of the brain
| Study group | Role | What they receive |
|---|---|---|
| Administration of CAR T-cells | Experimental | Dose escalation follows the standard 3+3 doseescalation design. A total of 3 dose levels are set for subjects. Receives: Drug: CAR-T cells; Procedure: Ommaya Reservoir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity (DLT)
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Measured: Baseline up to 28 days after CAR T-cells infusion
Incidence of treatment-emergent adverse events (TEAEs)
Incidence of treatment-emergent adverse events [Safety and Tolerability]
Measured: Up to 2 years after CAR T-cells infusion
Secondary outcomes (9)
B-cell acute lymphocytic leukemia(B-ALL), Overall response rate (ORR)
Assessment of ORR (ORR = CR + CRi) at Month 6, 12, 18 and 24
Measured: At Month 1, 3, 6, 12, 18 and 24
B-ALL, Overall survival (OS)
From the first infusion of CAR-T cells to death or the last visit
Measured: Up to 2 years after CAR-T cells infusion
B-ALL, Event-free survival (EFS)
From the first infusion of CAR-T cells to the occurrence of any event, including death, relapse orgene relapse, disease progression (any one occurs first), and the last visit
Measured: Up to 2 years after CAR-T cells infusion
B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR)
Assessment of ORR (ORR = CR + PR) per Lugano 2014 criteria
Measured: At Week 4, 12, and Month 6, 12, 18, 24
B-NHL, disease control rate (DCR)
Assessment of DCR (DCR=CR+PR+SD) per Lugano 2014 criteria
Measured: At Week 12 and Month 6, 12, 18, 24
Quality of life
Assessment of Quality of life using Research and Treatment of Cancer QOL Core Questionnaire 30 (EORTC QLQ-30) at Baseline, Month 1, 3, 6, 9 and 12
Measured: At Baseline, Month 1, 3, 6, 9 and 12
IADL score
Assessment of IADL score at Baseline, Month 1, 3, 6, 9 and 12
Measured: At Baseline, Month 1, 3, 6, 9 and 12
ADL score
Assessment of ADL score at Baseline, Month 1, 3, 6, 9 and 12
Measured: At Baseline, Month 1, 3, 6, 9 and 12
HADS score
Assessment of Hospital Anxiety and Depression Scale (HADS) score at Baseline, Month 1, 3, 6, 9 and 12
Measured: At Baseline, Month 1, 3, 6, 9 and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2020
- Study start1 Nov 2020 (estimated)
- Primary completion1 Nov 2023 (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 Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by Zhejiang UniversityThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhejiang University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, He Huang, Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04532203
- Sponsor's protocol ID
- CNSL-ZhejiangU
- Status last verified
- Oct 2020
- First submitted
- 20 Aug 2020
- Last updated
- 26 Oct 2020
- 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 26 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Trial for the Safety and Efficacy of CAR-T Cells Therapy for Patients With the Central Nervous System Involvement of Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia or B-cell Non-Hodgkin's Lymphoma
- ClinicalTrials.gov ID
- NCT04532203
- Acronym / sponsor ID
- CNSL-ZhejiangU
- Keywords
- Acute Lymphoblastic Leukemia, Non-Hodgkin's Lymphoma, CAR T-cell therapy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- Zhejiang UniversityUniversity, hospital or other
- Study start
- 1 Nov 2020 (estimated)
- Primary completion
- 1 Nov 2023 (estimated)
- Study completion
- 1 Nov 2026 (estimated)
- First posted
- 31 Aug 2020 (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.
A Study of CAR-T Cells Therapy for Patients With Relapsed and/or Refractory Central Nervous System Hematological Malignancies
Detailed description
This is a single arm, open-label, single-center study. This study is indicated for relapsed or refractory central nervous system CD19+ B-cell hematological malignancies, including acute lymphoblastic leukemia and B-cell non-Hodgkin's lymphoma. The selections of dose levels and the numberof subjects are based on clinical trialsof similar foreign products. Two groups of patients will be enrolled, 36 in eachgroup. Primary objective is to explore the safety, main consideration is dose-related safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Administration of CAR T-cells | Experimental | Drug: CAR-T cells, Procedure: Ommaya ReservoirDose escalation follows the standard 3+3 doseescalation design. A total of 3 dose levels are set for subjects. |
Who may qualify
- Ages
- 3 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (24 listed)
- Common inclusion criteria for B-ALL and B-NHL:
Key exclusion criteria (12 listed)
- History of craniocerebral trauma, conscious disturbance,epilepsy,cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;
- Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
- Pregnant (or lactating) women;
- Patients with severe active infections (excluding simple urinarytractinfectionand bacterial pharyngitis);
- Active infection of hepatitis B virus or hepatitis C virus;
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 cellsAlso: CAR-T cells injectionEach subject receive CAR T-cells by intravenous infusion | Drug | Administration of CAR T-cells |
| Ommaya ReservoirSurgical catheter placement into the fourth ventricle of the brain | Procedure or surgery | Administration of CAR T-cells |
Primary outcome
Dose-limiting toxicity (DLT)
Time frame: Baseline up to 28 days after CAR T-cells infusion
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Incidence of treatment-emergent adverse events (TEAEs)
Time frame: Up to 2 years after CAR T-cells infusion
Incidence of treatment-emergent adverse events [Safety and Tolerability]
9 secondary outcomes
B-cell acute lymphocytic leukemia(B-ALL), Overall response rate (ORR)
Time frame: At Month 1, 3, 6, 12, 18 and 24
B-ALL, Overall survival (OS)
Time frame: Up to 2 years after CAR-T cells infusion
B-ALL, Event-free survival (EFS)
Time frame: Up to 2 years after CAR-T cells infusion
B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR)
Time frame: At Week 4, 12, and Month 6, 12, 18, 24
B-NHL, disease control rate (DCR)
Time frame: At Week 12 and Month 6, 12, 18, 24
Quality of life
Time frame: At Baseline, Month 1, 3, 6, 9 and 12
IADL score
Time frame: At Baseline, Month 1, 3, 6, 9 and 12
ADL score
Time frame: At Baseline, Month 1, 3, 6, 9 and 12
HADS score
Time frame: At Baseline, Month 1, 3, 6, 9 and 12
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2020.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing CAR-T cells and Ommaya Reservoir in people with Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma, run by Zhejiang University at 1 site in China.
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 24 inclusion and 12 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 26 Oct 2020. 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 China. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 He Huang, PhD (86-13605714822, hehuangyu@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting toxicity (DLT) (time frame: Baseline up to 28 days after CAR T-cells infusion). The study lists 2 primary outcomes in all. 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 26 Oct 2020.