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

NCT04553393 | Unknown Phase 1

• 1 other identifier: CHN-PLAGH-BT-060
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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 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.).

Conditions

Refractory or Relapsed Aggressive r/r B-NHL With Huge Tumor Burden

Outcome Measures

Primary Outcomes (4)

• Adverse events after intervention

  Safety Outcome

  12 months

• Progression Free Survival

  2 years

• Duration of Response

  2 years

• Overall Survival

  2 years

Secondary Outcomes (2)

• Objective Response Rate Outcome Measure

  2 years

• Intervention treatment-related adverse events (AEs)

  12 months

Other Outcomes (1)

• Exploratory research

  12 months

Study Arms (4)

Decitabine-primed Tandem CAR19/20 engineered T cells

ACTIVE COMPARATOR

Tandem 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.

Biological: Decitabine-primed Tandem CAR19/20 engineered T cells

Decitabine-primed Tandem CAR19/20 engineered T cells plus chidamide

EXPERIMENTAL

Chidamide 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.

Drug: Chidamide; Biological: Decitabine-primed Tandem CAR19/20 engineered T cells

Decitabine-primed Tandem CAR19/20 engineered T cells plus decitabine

EXPERIMENTAL

Decitabine 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.

Drug: Decitabine; Biological: Decitabine-primed Tandem CAR19/20 engineered T cells

Decitabine-primed Tandem CAR19/20 engineered T cells plus chidamide+decitabine

EXPERIMENTAL

The 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

Drug: Chidamide and Decitabine; Biological: Decitabine-primed Tandem CAR19/20 engineered T cells

Interventions

Chidamide DRUG

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

Also known as: cohort 2

Decitabine-primed Tandem CAR19/20 engineered T cells plus chidamide

Decitabine DRUG

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

Also known as: cohort 3

Decitabine-primed Tandem CAR19/20 engineered T cells plus decitabine

Chidamide and Decitabine DRUG

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

Also known as: cohort 4

Decitabine-primed Tandem CAR19/20 engineered T cells plus chidamide+decitabine

Decitabine-primed Tandem CAR19/20 engineered T cells BIOLOGICAL

Tandem CAR19/20 engineered T cells

Also known as: cohort 1

Decitabine-primed Tandem CAR19/20 engineered T cells; Decitabine-primed Tandem CAR19/20 engineered T cells plus chidamide; Decitabine-primed Tandem CAR19/20 engineered T cells plus chidamide+decitabine; Decitabine-primed Tandem CAR19/20 engineered T cells plus decitabine

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (1)

Biotherapeutic Department of Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

RECRUITING

MeSH Terms

Interventions

N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; KPNA1 protein, human; Decitabine

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Weidong Han, M.D.

  Chinese PLA Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Weidong Han, M.D.

CONTACT

+861055499341; hanwdrsw@sina.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 10, 2020
• First Posted: September 17, 2020
• Study Start: September 9, 2020
• Primary Completion: September 8, 2021
• Study Completion: September 8, 2022
• Last Updated: December 4, 2020

Record last verified: 2020-12

Locations

CN (1)