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Diffuse Non-Hodgkin LymphomaPhase 1NCT04232826

A Clinical Trial of CNCT19 Cells in the Treatment of CD19 Positive Relapsed or Refractory Diffuse Non-Hodgkin Lymphoma

A Phase 1 study testing single dose of CNCT19 in people with Diffuse Non-Hodgkin Lymphoma, 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 diffuse Non-Hodgkin lymphoma. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Diffuse Non-Hodgkin Lymphoma
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
9 participants
Where
2 sitesChina
Study dates
15 Jan 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 70 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 75.
  • Relapsed or refractory NHL with CD19-positive after at least two systemic lines of therapy
  • Diffuse large B cell lymphoma (DLBCL) non-specific (NOS), T-cell / Histiocyte Rich large B-cell lymphoma, elderly EBV-positive diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma (PMBCL), chronic inflammation-associated DLBCL, follicular lymphoma (FL) transformed large B-cell lymphoma, high-grade B-cell lymphoma with MYC and BCL2 and / or BCL6 rearrangement and High-grade B-cell lymphoma-unspecified; b. 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 at least 4 courses of first-line treatment / at least 2 courses of end-line treatment (2 lines and above) with duration no longer than 6 month from last dose of therapy OR;
  • Refractory post-autologous stem cell transplant (ASCT); i. Disease progression or relapsed less than or equal to 12 months of ASCT (must have biopsy proven recurrence in relapsed individuals); ii. 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 stem cell transplantation (ASCT); c. Individuals must have received two systemic lines of therapy
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  • anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20-negative;
  • an anthracycline containing chemotherapy regimen;
  • FL-transformed DLBCL must have received pre-chemotherapy for FL and become resistant after conversion to DLBCL.
  • At least one measurable lesion, defined as at least 1 lymph node >1.5 cm in the longest diameter, per revised IWG Response Criteria.
  • Any previous systemic immune checkpoint therapy (such as anti-PD1 / PD-L1 monoclonal antibody, etc.), at least 3 half-lives away from the Cell Product Preparation; other systemic treatments should be stoped at least 2 weeks or 5 half-lives before Cell Product Preparation (shorter Whichever comes first).
  • Eastern cooperative oncology group (ECOG) performance status of 0 to 1.
  • Sufficient bone marrow reserves defined as:
  • Absolute neutrophil (ANC) > 1,000 / mm3;
  • Lymphocyte absolute value (ALC) ≥ 100 / mm3;
  • Platelet (PLT) ≥ 50,000 / mm3.
  • 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;
  • 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.
  • Patients who received chemotherapy within 2 weeks before CNCT19 infusion. The following situations are excluded:
  • Lymphodepleting Chemotherapy prescribed by the protocol;
  • CNS prophylaxis treatment must be stopped > 1 week prior to CNCT19 infusion.
  • Has had treatment with any prior anti-CD19 therapy.
  • Plans to receive autologous stem cell transplantation (ASCT) within 6 weeks before the CNCT19 infusion.
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  • 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, HCV-Ab, TP-Ab.
  • Patients who have previously received surgery within 4 weeks before the screening that was unsuitable for enrollment by the investigator's assessment.
  • Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease. 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 (except for Atrial fibrillation, Paroxysmal supraventricular tachycardia); d. QTc≥450ms (male)or QTc≥470ms (female)(QTcB=QT/RR1/2); 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.
  • Lymphoma affects the atrium or ventricle.
  • Clinical emergencies (such as intestinal obstruction or vascular compression) that requires urgent treatment due to obstruction or compression of lymphoma tumors during screening.
  • 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 < 12 weeks.
  • Patient in other interventional clinical studies within 3 months before the CNCT19 infusion, 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 diffuse Non-Hodgkin lymphoma.

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 diffuse Non-Hodgkin lymphoma. 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

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

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

    Dose C: 4.00 x 10^8 autologous CNCT19 transduced cells via intravenous infusion. Drug: Fludarabine Drug: Cyclophosphamide

Study groups in NCT04232826
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: CTCAE v5.0

    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 Partial Remission (PR)

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

    Measured: 3 months

  2. Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)

    Efficacy of CNCT19 as measured by ORR during the 28 days after CNCT19 infusion, which includes CR and PR.

    Measured: 28 days

  3. Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)

    Efficacy of CNCT19 as measured by ORR during the 2 months after CNCT19 infusion, which includes CR and PR.

    Measured: 2 months

  4. Overall Remission Rate (ORR), which includes Complete Remission (CR) and Partial Remission (PR)

    Efficacy of CNCT19 as measured by ORR during the 6 months after CNCT19 infusion, which includes CR and PR.

    Measured: 6 months

  5. Best Overall Response (BOR)

    The best overall response after CNCT19 infusion.

    Measured: 24 months

  6. Time to initial Response (TTR)

    TTR is defined as the time from the CNCT19 infusion to the first documented CR or PR.

    Measured: 6 months

  7. Progression-free survival (RFS)

    PFS is defined as the time from the signing of informed consent form to the date of the documented progressive disease(PD) or death due to any cause.

    Measured: 24 months

  8. Duration of remission (DOR)

    DOR is defined as the time from the first documented CR or PR to the date of the first documented relapse or PD.

    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 start15 Jan 2020
  3. Primary completion1 Jan 2021
  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
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04232826
Sponsor's protocol ID
HY-CD19 CART-002
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 Diffuse Non-Hodgkin Lymphoma, 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 25 inclusion and 23 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 NCT04232826.

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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