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
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. Contact the study team or a site near you to ask about taking part.
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.
- 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