AzTrials
AzTrials

Refractory or Relapsed Aggressive r/r B-NHL With Huge Tumor BurdenPhase 1/2NCT04553393

Decitabine-primed Tandem CD19/CD20 CAR T Cells Plus Epigenetic Agents in Aggressive r/r B-NHL With Huge Tumor Burden

A Phase 1/2 study testing Chidamide, Decitabine and Chidamide and Decitabine in people with Refractory or Relapsed Aggressive r/r B-NHL With Huge Tumor Burden, run by Chinese PLA General Hospital at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

This open-label, multi-cohorts, phase 1/2 study has the primary objective of comparing decitabine-primed tandem CART 19/20 solo, with decitabine-primed tandem CART 19/20 plus chidamide, decitabine-primed tandem CART 19/20 plus decitabine, and decitabine-primed tandem CART 19/20 plus decitabine+chidamide in patients… Read more about this study

Who is it for?
Ages 16 to 65 years
What is being tested?
Chidamide, Decitabine and Chidamide and Decitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
1 siteChina
Study dates
9 Sep 2020to 8 Sep 2022
Phase
Phase 1/2
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 16 to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Age ≥16 and ≤ 65 years.
  • Sum of the Product of the perpendicular Diameters for multiple lesions, SPD ≥ 100cm^2 or the largest-diameter of tumor ≥ 10cm.
  • Histologically confirmed CD20+ and/or CD19+ aggressive B-cell non-Hodgkin lymphoma (NHL), including the following types defined by the World Health Organization (WHO) 2016:
  • Diffuse large B-cell lymphoma (DLBCL).
  • High grade B-cell lymphoma(HGBL).
  • Other aggressive B-cell lymphoma.
Show all 31Show fewer
  • Refractory disease or relapse after treatment with ≥2 lines of chemotherapy, including rituximab and anthracycline and either having failed autologous hematopoietic stem cell transplantation (HSCT), being ineligible for autologous HSCT or not consenting to autologous HSCT.
  • We defined chemotherapy-refractory disease as meeting one or more of the following criteria:
  • No response to first-line therapy (primary refractory disease).
  • No response to second-line or later therapy.
  • Progressive disease (PD) as the best response to the most recent therapy regimen.
  • Stable disease (SD) as the best response after at least 2 cycles of the most recent line of therapy with an SD duration of no longer than 6 months from the last dose of therapy.
  • Failure following autologous HSCT was defined as follows:
  • PD or relapsed disease ≤12 months after autologous stem cell transplantation (ASCT) (requires biopsy-proven recurrence in relapsed subjects).
  • No response or relapse after salvage therapy is given post-ASCT.
  • PD or relapse ≥3 months after treatment with targeted CD19 therapy, including CD19 CAR T cells or anti-CD19/anti-CD3.
  • Successful leukapheresis assessment and preculture of T cells.
  • Life expectancy > 3 months.
  • Adequate organ function:
  • Creatinine < 1.6 mg/dL (140 µmol/L) or creatinine clearance ≥60 mL/min.
  • Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 3× upper limit of the normal range.
  • Bilirubin <2.0 mg/dL unless the subject had Gilbert's syndrome (<3.0 mg/dL).
  • A minimum level of pulmonary reserve defined as ≤ grade 1 dyspnoea and pulse oxygenation > 91% with room air.
  • Cardiac ejection fraction ≥50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings.
  • An adequate bone marrow reserve defined as:
  • Absolute neutrophil count (ANC)>1,000/mm3.
  • Absolute lymphocyte count (ALC)≥300/mm3.
  • Platelet count ≥ 50,000/mm3.
  • Haemoglobin > 7.0 mg/dL.
  • Measurable or assessable disease according to the "IWG Response Criteria for Malignant Lymphoma" (Cheson 2014). Patients in complete remission (CR) with no evidence of disease were not eligible.
  • Informed consent/assent requiring that all patients have the ability to understand and the willingness to provide written informed consent.

Who cannot join

  • Patients with definite involvement of the gastrointestinal tract. Endoscopy should be performed to confirm gastrointestinal involvement in suspected patients. However, patients with central nervous system (CNS) involvement were cautiously enrolled in this clinical study.
  • Detection of a clear HAMA effect in patients with prior CD19 CAR T cell treatment failure or recurrence, or negative tumour puncture detection of CD19 and CD20.
  • Pregnant or lactating women.
  • Uncontrolled active bacterial or viral infection (active hepatitis B or hepatitis C infection, HIV infection) or treponema pallidum infection.
  • Class III/IV cardiovascular disability according to the New York Heart Association Classification and a cardiac ejection fraction ≥50%.
  • History of allo-HSCT.
Show all 12Show fewer
  • Requirement for urgent therapy due to tumour mass effects such as respiratory obstruction or blood vessel compression.
  • Current or expected need for systemic corticosteroid therapy.
  • Any organ failure.
  • Patients with a second tumour requiring therapy or intervention.
  • Eastern Cooperative Oncology Group (ECOG) performance status score between 0 and 2.
  • Subjects considered unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation according to the investigator's judgement.

Trial locations and contacts

1 site in 1 country.

Weidong Han, M.D. contact

+861055499341

hanwdrsw@sina.com

China1 site, 1 recruiting

  • Biotherapeutic Department of Chinese PLA General Hospital

    Beijing, Beijing Municipality, 100853

    Weidong Han, M.D, +86-10-66937463, hanwdrsw@sina.com

    Weidong Han, M.D

    Recruiting

Other trials in China

About this study

Official title: Treatment of Decitabine-primed Tandem Targeting CD19 and CD20 Chimeric Antigen Receptor T Cells Plus Epigenetic Agents in Aggressive Relapsed and/or Refractory Non-Hodgkin's Lymphoma Patients With Huge Tumor Burden

This open-label, multi-cohorts, phase 1/2 study has the primary objective of comparing decitabine-primed tandem CART 19/20 solo, with decitabine-primed tandem CART 19/20 plus chidamide, decitabine-primed tandem CART 19/20 plus decitabine, and decitabine-primed tandem CART 19/20 plus decitabine+chidamide in patients with aggressive B-NHL who were confirmed as Relapsed and/or Refractory B cell Non-Hodgkin's Lymphoma with hugh tumor burden (Sum of the Product of the perpendicular Diameters for multiple lesions, SPD ≥ 100cm^2 or the largest-diameter of tumor ≥ 10 cm.).

Being tested
Chidamide, Decitabine, Chidamide and Decitabine, Decitabine-primed Tandem CAR19/20 engineered T cells

What participants receive

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

  • ChidamideDrug

    Also called cohort 2

    Chidamide will be added 1 month after responding to CART cells infusion

  • DecitabineDrug

    Also called cohort 3

    Decitabine will be added 1 month after responding to CART cells infusion

  • Chidamide and DecitabineDrug

    Also called cohort 4

    Both chidamide and decitabine will be added 1 month after responding to CART cells infusion

  • Decitabine-primed Tandem CAR19/20 engineered T cellsBiological

    Also called cohort 1

    Tandem CAR19/20 engineered T cells

Study groups in NCT04553393
Study groupRoleWhat they receive
Decitabine-primed Tandem CAR19/20 engineered T cellsActive comparatorTandem dual Specificity targeting CD19 and CD20 decitabine-primed CAR-T cells can recognize and kill the CD19 negative malignant cells through recognition of CD20 and improve the possibility of killing lymphoma tumor cells.
Receives: Biological: Decitabine-primed Tandem CAR19/20 engineered T cells
Decitabine-primed Tandem CAR19/20 engineered T cells plus chidamideExperimentalChidamide is a novel and orally active benzamide class of HDAC inhibitor that selectively inhibits activity of HDAC1, 2, 3 and 10, which can Induce tumor-cell apoptosis, suppress cell proliferation and enhance immune surveillance.
Receives: Drug: Chidamide; Biological: Decitabine-primed Tandem CAR19/20 engineered T cells
Decitabine-primed Tandem CAR19/20 engineered T cells plus decitabineExperimentalDecitabine is an investigational (experimental) drug that works by depleting DNA methyltransferase 1(DNMT1), which can increase tumor antigens and HLA expression, enhances antigen processing, promotes T cell infiltration, and boosts effector T cell function.
Receives: Drug: Decitabine; Biological: Decitabine-primed Tandem CAR19/20 engineered T cells
Decitabine-primed Tandem CAR19/20 engineered T cells plus chidamide+decitabineExperimentalThe combination of chidamide and decitabine can increase tumor antigens and HLA expression, enhances antigen processing, promotes T cell infiltration, and boosts effector T cell function, induce tumor-cell apoptosis, suppress cell proliferation and enhance immune surveillance
Receives: Drug: Chidamide and Decitabine; Biological: Decitabine-primed Tandem CAR19/20 engineered T cells

What is being measured

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

  1. Adverse events after intervention

    Safety Outcome

    Measured: 12 months

  2. Progression Free Survival

    Measured: 2 years

  3. Duration of Response

    Measured: 2 years

  4. Overall Survival

    Measured: 2 years

Secondary outcomes (2)

  1. Objective Response Rate Outcome Measure

    ORR assess by investigators per the 2014 Lugano classification rate of subjects achieved objective response in all evaluable subjects

    Measured: 2 years

  2. Intervention treatment-related adverse events (AEs)

    Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0

    Measured: 12 months

Timeline

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

  1. First posted17 Sep 2020
  2. Study start9 Sep 2020
  3. Primary completion8 Sep 2021 (estimated)
  4. Study completion8 Sep 2022 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04553393
Sponsor's protocol ID
CHN-PLAGH-BT-060
Status last verified
Dec 2020
First submitted
10 Sep 2020
Last updated
4 Dec 2020
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Chidamide, Decitabine and Chidamide and Decitabine in people with Refractory or Relapsed Aggressive r/r B-NHL With Huge Tumor Burden, run by Chinese PLA General Hospital 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 31 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 4 Dec 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 Weidong Han, M.D. (+861055499341, hanwdrsw@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse events after intervention (time frame: 12 months). The study lists 4 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 NCT04553393.

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 4 Dec 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in