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Relapsed or Refractory Acute Lymphoblastic LeukemiaPhase 1NCT04230473

A Clinical Trial of CNCT19 Cells in the Treatment of CD19 Positive Relapsed or Refractory Acute Lymphoblastic Leukemia

A Phase 1 study testing single dose of CNCT19 in people with Relapsed or Refractory Acute Lymphoblastic Leukemia, run by Juventas Cell Therapy Ltd. at 2 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a single arm, open-label, non-randomized, dose-escalation, phase I study to determine the safety and efficacy of CNCT19 in adult patients with relapsed or refractory acute lymphoblastic leukemia. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
single dose of CNCT19
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
2 sitesChina
Study dates
13 Mar 2020to 1 Nov 2022
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 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Informed consent is signed by the subject.
  • Age 18 to 65.
  • Relapsed or refractory ALL
  • Relapse within 12 months of first remission;
  • Without remission after more than 6 weeks of induction chemotherapy or without remission after 2 cycles of induction chemotherapy regimen;
  • 2nd or greater Bone Marrow (BM) relapse OR;
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  • First relapse after chemotherapy, without remission after at least 1 rescue treatment;
  • Any BM relapse after autologous stem cell transplantation (SCT).
  • Documentation of 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 1 generation and/or 2 generation of tyrosine kinase inhibitor therapy (TKI); no TKI salvage treatments if the patient has a T315I mutation.
  • Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening.
  • Eastern cooperative oncology group (ECOG) performance status of 0 to 1.
  • Adequate organ function defined as:
  • aspartate aminotransferase (AST) ≤ 3 upper limit of normal (ULN);
  • Serum alanine aminotransferase (ALT) ≤ 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.
  • Have appropriate vascular conditions for apheresis.
  • Non-hematological toxic reactions (excluding diseases related) caused by previous treatment were restored to ≤ 1 level before screening (excluding ≤ 2 level of neurotoxicity caused by hair loss and chemotherapy drugs).
  • Women of childbearing age have a negative blood / urine pregnancy test within 7 days before the CNCT19 infusion. Women of child-bearing potential and all male participants must use highly effective methods of contraception throughout the study and for a period of at least six months after the CNCT19 infusion.

Who cannot join

  • Active CNS involvement by malignancy.
  • Isolated extra-medullary disease relapse.
  • Patients who received chemotherapy within 2 weeks before CNCT19 infusion. The following situations are excluded:
  • Lymphodepleting Chemotherapy prescribed by the protocol;
  • Tyrosine kinase inhibitors (TKI) and hydroxyurea must be stopped > 72 hours prior to CNCT19 infusion;
  • The following drugs must be stopped > 1 week prior to CNCT19 infusion: 6-mercaptopurine, 6-thioguanine, methotrexate (<25 mg / m2), cytosine arabinoside (<100 mg / m2 / d), vincristine, asparaginase;
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  • Pegylated-asparaginase must be stopped > 4 weeks prior to CNCT19 infusion;
  • CNS prophylaxis treatment must be stopped > 1 week prior to CNCT19 infusion.
  • Radiotherapy before CNCT19 infusion:
  • Non-CNS site of radiation completed < 2 weeks prior to CNCT19 infusion; CNS directed radiation completed < 8 weeks prior to CNCT19 infusion.
  • Therapeutic systemic doses of steroids were stopped < 72 hours prior to CNCT19 infusion. However, the following physiological replacement doses of steroids are allowed: < 10 mg/day hydrocortisone or equivalent.
  • Has had treatment with any prior CAR-T therapy.
  • Patients who have previously received allogeneic hematopoietic stem cell transplantation (allo-HSCT).
  • 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 HBsAg, HBeAg, HBeAb, HBcAb, HCV-Ab, TP-Ab.
  • Active malignancy. Patients with Prior malignancy that has been cured for ≥ 2 years are excluded.
  • a. Left Ventricular Ejection Fraction (LVEF) ≤45%; b. III/IV congestive heart failure (NYHA); c. Severe arrhythmia ; QTc≥450ms (male)or QTc≥470ms (female)(QTcB=QT/RR1/2); d.Uncontrolled hypertension (systolic blood pressure ≥140 mmHg and / or diastolic blood pressure ≥90 mmHg) or pulmonary hypertension or unstable angina; e. Myocardial infarction or Coronary Artery Bypass Graft Surgery, heart stent surgery < 6 months prior to CNCT19 infusion; f. Clinically significant valvular disease; g. Other heart diseases that have been judged by the investigator to be unsuitable for receiving cell therapy.
  • Clinically significant pleural effusion.
  • Patients with a history of epilepsy, cerebrovascular ischemia / hemorrhage, cerebellar disease or other active central nervous system diseases.
  • History of deep vein thrombosis or pulmonary embolism within 6 months of screening.
  • Known history of hypersensitivity to ingredients used in the drug.
  • 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 < 3 months.
  • Patient in other interventional clinical studies within 3 months before screening, who have received active drug therapy, or who intend to participate in another clinical trial or receive anti-tumor therapy outside the protocol during the entire study.
  • Patients with other conditions making the patients unsuitable for receiving cell therapy as judged by the investigator.

Trial locations and contacts

2 sites in 1 country.

China2 sites

  • Institute of Hematology & Blood Diseases Hospital

    Tianjin, 300020

  • Henan Cancer Hospital

    Zhengzhou, Henan

Other trials in China

About this study

This is a single arm, open-label, non-randomized, dose-escalation, phase I study to determine the safety and efficacy of CNCT19 in adult patients with relapsed or refractory acute lymphoblastic leukemia.

Read the detailed description

This is a single arm, open-label, non-randomized, dose-escalation, phase I study to determine the safety and efficacy of CNCT19 in adult patients with relapsed or refractory acute lymphoblastic leukemia. 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
single dose of CNCT19
Medical subject headings
Recurrence, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • single dose of CNCT19Biological

    Dose A: 0.25 x 10^8 autologous CNCT19 transduced cells via intravenous infusion. Drug: Fludarabine Drug: Cyclophosphamide

    Dose B: 1.00 x 10^8 autologous CNCT19 transduced cells via intravenous infusion. Drug: Fludarabine Drug: Cyclophosphamide

    Dose C: 2.00 x 10^8 autologous CNCT19 transduced cells via intravenous infusion. Drug: Fludarabine Drug: Cyclophosphamide

Study groups in NCT04230473
Study groupRoleWhat they receive
Single dose of CNCT19ExperimentalA conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CNCT19.
Receives: Biological: single dose of CNCT19

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) and Recommended Phase II Dose (RP2D)

    Determine the MTD and DLT of CNCT19 in the Treatment and recommend the dose for Phase II study.

    Measured: 28 days

  2. Safety of CNCT19 therapy

    Safety measures include adverse events as assessed by CTCAE v5.0.

    Measured: 24 months

Secondary outcomes (9)

  1. Overall Remission Rate (ORR), which includes Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi)

    Efficacy of CNCT19 as measured by ORR during the 3 months after CNCT19 infusion, which includes CR and CRi.

    Measured: 3 months

  2. Overall Remission Rate (ORR)

    Description: ORR includes CR and CRi.

    Measured: 28 days

  3. Overall Remission Rate (ORR) with minimal residual disease (MRD) negative bone marrow

    MRD negative status as determined by central laboratory using multi-parameter flow cytometry.

    Measured: 28 days

  4. Overall Remission Rate (ORR) with minimal residual disease (MRD) negative bone marrow

    MRD negative status as determined by central laboratory using multi-parameter flow cytometry.

    Measured: 3 months

  5. Overall Remission Rate (ORR)

    ORR includes CR and CRi.

    Measured: 6 months

  6. Overall Remission Rate (ORR) with minimal residual disease (MRD) negative bone marrow

    MRD negative status as determined by central laboratory using multi-parameter flow cytometry.

    Measured: 6 months

  7. Duration of remission (DOR)

    DOR is defined as the time from the first documented CR or Partial Remission (PR) to the date of the first documented progressive disease(PD) or death due to any cause.

    Measured: 24 months

  8. Relapse-free survival (RFS)

    RFS is defined as the time from the documented CR or PR after the CNCT19 infusion to the date of the documented PD or death due to any cause.

    Measured: 24 Months

  9. Overall survival (OS)

    OS is defined as the time from the signing of informed consent form to the date of the last survival follow-up or death due to any cause.

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jan 2020
  2. Study start13 Mar 2020
  3. Primary completion1 Dec 2020
  4. Study completion1 Nov 2022

Resources

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
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04230473
Sponsor's protocol ID
HY-CD19 CART-001
Status last verified
Mar 2023
First submitted
11 Jan 2020
Last updated
28 Mar 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing single dose of CNCT19 in people with Relapsed or Refractory Acute Lymphoblastic Leukemia, run by Juventas Cell Therapy Ltd. at 2 sites 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 22 inclusion and 26 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: finished, as of the sponsor's last update on 28 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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?

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) and Recommended Phase II Dose (RP2D) (time frame: 28 days). 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?

On the ClinicalTrials.gov record for NCT04230473.

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 28 Mar 2023.

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