Relapsed or Refractory Hematological MalignanciesEarly Phase 1NCT04011293
A Clinical Study of Anti-CD19 Chimeric Antigen Receptor T-Cell Injection (CNCT19) in the Treatment of Cluster of Differentiation 19 (CD19) Positive Relapsed or Refractory B Cell Malignancies
A Early Phase 1 study testing CNCT19 in people with Relapsed or Refractory Hematological Malignancies, run by Shandong University at 1 site in China.
Trial summary
This is a single arm, open-label, single center study to determine the safety and efficacy of CNCT19 in adult patients with Relapsed or Refractory B cell Malignancies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed or Refractory Hematological Malignancies
- What is being tested?
- CNCT19
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- Jul 2019to Apr 2022
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed consent is signed by a subject or his lineal relation.
- Age 18 or older.
- Relapsed or refractory B-cell lineage acute lymphoblastic leukemia (B-ALL)
- Relapsed or refractory
- Relapse within 12 months of first remission
- Without remission after 2 cycles of induction chemotherapy regimen.
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- Without remission after more than 6 weeks of induction chemotherapy.
- 2nd or greater Bone Marrow (BM) relapse
- Any BM relapse after autologous/allogeneic stem cell transplantation (SCT)
- documentation of cluster of differentiation 19 (CD19) tumor expression demonstrated in bone marrow or peripheral blood within 3 months of study entry.
- Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are intolerant to or have failed 1generation and/or 2 generation of tyrosine kinase inhibitor therapy (TKI); no TKI salvage treatments if the patient has a BCR-ABL1 kinase domain gatekeeper mutation Thr315Ile (T315I) mutation.
- Bone marrow with ≥ 5% lymphoblasts by morphologic assessment or minimal residual disease (MRD) positive at screening
- Relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) with CD19-positive after two systemic lines of therapy
- Chemotherapy-refractory disease, defined as one of more of the following:
- No response to last line of therapy. i. Progressive disease (PD) as best response to most recent therapy regimen. ii. Stable disease (SD) as best response to most recent therapy with duration no longer than 6 month from last dose of therapy
- Refractory post-autologous stem cell transplant (ASCT) or allogeneic stem cell transplantation (allo-HSCT).
- Disease progression or relapsed less than or equal to 12 months of ASCT /allo-HSCT (must have biopsy proven recurrence in relapsed individuals).
- If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy Any BM relapse after autologous/allogeneic stem cell transplantation (SCT).
- Individuals must have received two systemic lines of therapy
- anti-cluster of differentiation 20 (CD20) monoclonal antibody unless investigator determines that tumor is CD20-negative and
- an anthracycline containing chemotherapy regimen
- Relapsed or refractory chronic lymphocytic leukemia (CLL) with CD19-positive Diagnosis of CLL that meets 2008 the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) diagnostic criteria, must have at least one of the following criteria.
- Patients with Del(17p) / tumour suppressor p53 (TP53) mutation
- CLL relapsed or refractory after 2 or more lines of therapy, Relapsed is defined as evidence of disease progression after a period of 6 months or more following an initial CR or PR.
- Refractory disease is defined as failure to achieve a response after 6 cycles of induction chemotherapy or having disease progression within 6 months of the last treatment.
- At least one measurable lesion, defined as at least 1 lymph node >1.5 cm in the longest diameter, per revised IWG Response Criteria.
- Eastern cooperative oncology group (ECOG) performance status of 0 to 2.
- Adequate organ function defined as:
- Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤3 upper limit of normal (ULN)
- Total bilirubin ≤ 2 ULN, except in individuals with Gilbert's syndrome; Note: Patients with Gilbert's syndrome that bilirubin ≤ 3 ULN and direct bilirubin ≤ 1.5 ULN will be eligible.
- A serum creatinine≤ 1.5 ULN or Creatine removal rate ≥ 60mL/min（Cockcroft and Gault）
- Must have a minimum level of pulmonary reserve as ≤ Grade 1 dyspnea and oxygen saturation > 91% on room air.
- International normalized ratio (INR) ≤ 1.5 ULN and activated partial thromboplastin time (APTT) ≤ 1.5 ULN.
- Women of child-bearing potential and all male participants must use highly effective methods of contraception for a period of 1 year after the CNCT19 infusion.
Who cannot join
- Active central nervous system (CNS) involvement by malignancy.
- Patients with systemic vasculitis (such as Wegener granulomatosis, nodular polyarteritis, systemic lupus erythematosus) and active or uncontrolled autoimmune disease (such as autoimmune hemolytic anemia, etc.)
- Patients who are positive for any of HIV antibody, TP antibody, hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) antibody.
- During the first four weeks of screening, the patient underwent major surgery which was assessed by the investigator as unsuitable for enrollment;
- The patient's heart fits any of the following conditions:
- Left Ventricular Ejection Fraction (LVEF) ≤45%; III/IV congestive heart failure (NYHA); Severe arrhythmia (except for Atrial fibrillation, Paroxysmal supraventricular tachycardia); corrected QT interval (QTc)≥450ms (male)or QTc≥470ms (female)（QTc using Bazett's(QTcB)=QT/RR^0.5）; Myocardial infarction or Coronary Artery Bypass Graft Surgery, heart stent surgery.
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- Other heart diseases that have been judged by the investigator to be unsuitable for receiving cell therapy.
- Patients with a history of epilepsy or other active central nervous system diseases.
- Has had treat with live vaccine within 6 weeks prior to screening；
- Patients with evidence of currently uncontrollable serious active infections (e.g., sepsis, bacteremia, fungemia, viremia, etc.).
- Life expectancy < 12 weeks.
- Patients with other conditions making the patients unsuitable for receiving cell therapy as judged by the investigator.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Qilu Hospital of Shandong University
Jinan, Shandong, 250012
Chuanli Zhao, Dr., +86 185 6008 7009, chuanlizhao@163.com
Chunyan Ji, Dr.
About this study
Official title: A Clinical Study of CNCT19 Cells in the Treatment of CD19 Positive Relapsed or Refractory B Cell Malignancies
This is a single arm, open-label, single center study to determine the safety and efficacy of CNCT19 in adult patients with Relapsed or Refractory B cell Malignancies.
Read the detailed description
This is a single arm, open-label, single-center study to determine the safety and efficacy of CNCT19 in adult patients with r/r B cell Malignancies. The study will have the following sequential phases: Screening, Pre-Treatment (Cell Product Preparation \& Lymphodepleting Chemotherapy), Treatment and Follow-up, and Survival Follow-up. The total duration of the study is 2 years from CNCT19 cell infusion.
- Being tested
- CNCT19
- Keywords
- Relapsed, Refractory, Malignancy
- Medical subject headings
- Recurrence, Hematologic Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CNCT19Biological
0.5 to 4 x 10^6 autologous CNCT19 transduced cells per kg body weight, with a maximum dose of 4 x 10^8 autologous CNCT19 transduced cells via intravenous infusion.
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Single dose of CNCT19 Receives: Biological: CNCT19 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Measured: 24 months
Overall remission rate (ORR)
Measured: 3 months
Secondary outcomes (10)
Response at Day 28±3 days
Measured: 1 month
Percentage of patients who achieve complete remission (CR) or complete remission with incomplete blood count recovery (CRi) (partial remission，PR) at month 6 without SCT between CNCT19 infusion and Month 6 response assessment.
Measured: 6 months
Percentage of patients who achieve CR or CRi (PR) with minimal residual disease negative bone marrow.
Measured: 6 months
Relapse-free survival
Measured: 24 months
Progression-free survival
Measured: 24 months
Percentage of patients who achieve best overall response (BOR)
Measured: 24 months
Duration of remission (DOR)
Measured: 24 months
Overall survival
Measured: 24 months
Percentage of patient who achieve CR or CRi (PR) and then proceed to stem cell transplantation（SCT） while in remission.
Measured: 24 months
Proportion of patients with detectable replication competent lentivirus (RCL) by vesicular stomatitis virus, glycoprotein (VSV-G)
Measured: at Month 3 post treatment then Month 6 and Month12, yearly until year 15 if CD19 chimeric antigen receptor (CAR) transgene is still detected
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2019
- Study startJul 2019 (estimated)
- Primary completionJul 2020 (estimated)
- Study completionApr 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or Refractory Hematological MalignanciesStudies 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
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shandong University
- Sponsor type
- University, hospital or other
- Collaborators
- Juventas Cell Therapy Ltd.
- Responsible party
- Principal investigator, Chunyan Ji, Shandong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04011293
- Sponsor's protocol ID
- HY001003
- Status last verified
- Jul 2019
- First submitted
- 3 Jul 2019
- Last updated
- 8 Jul 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Study of CNCT19 Cells in the Treatment of CD19 Positive Relapsed or Refractory B Cell Malignancies
- ClinicalTrials.gov ID
- NCT04011293
- Acronym / sponsor ID
- HY001003
- Keywords
- Relapsed, Refractory, Malignancy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Shandong UniversityUniversity, hospital or other
- Collaborators
- Juventas Cell Therapy Ltd.
- Study start
- Jul 2019 (estimated)
- Primary completion
- Jul 2020 (estimated)
- Study completion
- Apr 2022 (estimated)
- First posted
- 8 Jul 2019 (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.
This is a single arm, open-label, single center study to determine the safety and efficacy of CNCT19 in adult patients with Relapsed or Refractory B cell Malignancies.
Detailed description
This is a single arm, open-label, single-center study to determine the safety and efficacy of CNCT19 in adult patients with r/r B cell Malignancies. The study will have the following sequential phases: Screening, Pre-Treatment (Cell Product Preparation \& Lymphodepleting Chemotherapy), Treatment and Follow-up, and Survival Follow-up. The total duration of the study is 2 years from CNCT19 cell infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Biological: CNCT19Single dose of CNCT19 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- Informed consent is signed by a subject or his lineal relation.
- Age 18 or older.
- Relapsed or refractory B-cell lineage acute lymphoblastic leukemia (B-ALL)
- Relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) with CD19-positive after two systemic lines of therapy
- Relapsed or refractory chronic lymphocytic leukemia (CLL) with CD19-positive Diagnosis of CLL that meets 2008 the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) diagnostic criteria, must have at least one of the following criteria.
Key exclusion criteria (12 listed)
- Active central nervous system (CNS) involvement by malignancy.
- Patients with systemic vasculitis (such as Wegener granulomatosis, nodular polyarteritis, systemic lupus erythematosus) and active or uncontrolled autoimmune disease (such as autoimmune hemolytic anemia, etc.)
- Patients who are positive for any of HIV antibody, TP antibody, hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) antibody.
- During the first four weeks of screening, the patient underwent major surgery which was assessed by the investigator as unsuitable for enrollment;
- The patient's heart fits any of the following conditions:
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 |
|---|---|---|
| CNCT190.5 to 4 x 10^6 autologous CNCT19 transduced cells per kg body weight, with a maximum dose of 4 x 10^8 autologous CNCT19 transduced cells via intravenous infusion. | Biological | A |
Primary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: 24 months
Overall remission rate (ORR)
Time frame: 3 months
10 secondary outcomes
Response at Day 28±3 days
Time frame: 1 month
Percentage of patients who achieve complete remission (CR) or complete remission with incomplete blood count recovery (CRi) (partial remission，PR) at month 6 without SCT between CNCT19 infusion and Month 6 response assessment.
Time frame: 6 months
Percentage of patients who achieve CR or CRi (PR) with minimal residual disease negative bone marrow.
Time frame: 6 months
Relapse-free survival
Time frame: 24 months
Progression-free survival
Time frame: 24 months
Percentage of patients who achieve best overall response (BOR)
Time frame: 24 months
Duration of remission (DOR)
Time frame: 24 months
Overall survival
Time frame: 24 months
Percentage of patient who achieve CR or CRi (PR) and then proceed to stem cell transplantation（SCT） while in remission.
Time frame: 24 months
Proportion of patients with detectable replication competent lentivirus (RCL) by vesicular stomatitis virus, glycoprotein (VSV-G)
Time frame: at Month 3 post treatment then Month 6 and Month12, yearly until year 15 if CD19 chimeric antigen receptor (CAR) transgene is still detected
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2019.
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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 CNCT19 in people with Relapsed or Refractory Hematological Malignancies, run by Shandong 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 34 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 8 Jul 2019. 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 Chuanli Zhao, Dr. (+86 185 6008 7009, chuanlizhao@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 (time frame: 24 months). 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 8 Jul 2019.