Decitabine-primed Tandem CD19/CD20 CAR T Cells Treatment in r/r B-NHL

NCT04697940 | Active Not Recruiting Phase 1

• 1 other identifier: CHN-PLAGH-BT-058
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, phase 1/2 study has the primary objective of decitabine-primed tandem CART 19/20 in patients with B-NHL who were confirmed as r/r B cell Non-Hodgkin's Lymphoma. A total of 19 to 33 patients are planned to be enrolled and receive decitabine-primed tandem CART 19/20 cell infusion. Phase 1 (9 to 18 cases) is dose escalation part, and phase 2 (10 to 15 cases) is expansion cohort part.

Conditions

Relapsed and Refractory B-cell Non-Hodgkin's Lymphoma; Decitabine-primed Tandem CD19/CD20 CAR T Cells

Outcome Measures

Primary Outcomes (5)

• Phase 1: Incidence of Adverse Events (AEs)

  AE is defined as any adverse medical event from the date of randomization to 12 months after CAR T cells infusion. Among them, CRS and ICANS were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0.

  12 months

• Phase 1: Incidence of Dose-Limiting Toxicities (DLTs)

  DLT was defined as CAR T cells-related events with onset within first 28 days following infusion: The development of Grade (G) 3 or higher grade CRS lasting \> 2 weeks; Any CAR T cells-related AE requiring intubation; All G4 non-hematologic toxicities.

  First infusion date of CAR T cells up to 28 days

• Phase 1: Maximum tolerated dose (MTD)

  MTD is defined as the highest dose level of less than or equal to 2 DLT among the 6 subjects finally determined.

  12 months

• Phase 1: Recommended phase 2 dose (RP2D)

  The recommended dose for phase 2 was determined through phase 1 study.

  12 months

• Phase 2: Best Response Rate

  The incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as the best response to treatment assessed by investigators and based on the Lugano 2014 assessment criterion.

  12 months

Secondary Outcomes (7)

• Phase 2: Overall Survival (OS)

  24 months

• Phase 2: Progression Free Survival (PFS)

  24 months

• Phase 2: Time to response (TTR)

  24 months

• Phase 2: Duration of Response (DOR)

  24 months

• Pharmacokinetics: Number and copy number of CAR T cells (phase 1 and phase 2)

  12 months

Other Outcomes (2)

• Relationship between infusion dose of CAR T cells and efficacy

  12 months

• To analyze the dynamic changes of CAR T cells after infusion

  12 months

Study Arms (1)

Refractory or Relapsed Non-Hodgkin's Lymphoma

EXPERIMENTAL

A conditioning chemotherapy regimen of fludarabine and cyclophosphamide (FC regimen) will be administered followed by investigational treatment, autologous decitabine-primed Tandem CAR19/20 engineered T cells. Post leukapheresis, administration of short half-life chemo-agents, Bruton tyrosine kinase inhibitor (BTKi) and/or dexamethasone should be considered to bridge the following FC regimen in patients with bulky tumor burden, rapidly aggressive progression, and/or indications of imperious symptom control.

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

Interventions

Decitabine-primed Tandem CAR19/20 engineered T cells BIOLOGICAL

Phase I dose escalation (3+3) : dose 1 (0.5 × 10\^6 cells per kg) dose 2 (2 × 10\^6 cells per kg) dose 3 (5 × 10\^6 cells per kg) Phase II: Appropriate dose

Refractory or Relapsed Non-Hodgkin's Lymphoma

Fludarabine DRUG

Intravenous fludarabine 25-30 mg/m\^2/day on days -5, -4, and -3.

Also known as: Fludarabine Phosphate for Injection

Refractory or Relapsed Non-Hodgkin's Lymphoma

Cyclophosphamide DRUG

Intravenous cyclophosphamide 300-500 mg/m\^2/day on days -5, -4, and -3.

Also known as: Cyclophosphamide for Injection

Refractory or Relapsed Non-Hodgkin's Lymphoma

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 and ≤75 years.
• Eastern Cooperative Oncology Group (ECOG) performance status score between 0 and 2.
• Patients with histologically confirmed CD20+ and/or CD19+ B-cell NHL, including the following types defined by the World Health Organization (WHO) 2016:
• Diffuse large B-cell lymphoma not otherwise specified (DLBCL-NOS), including Activated B-cell type (ABC) / Germinal center B-cell Type (GCB);
• Primary mediastinal (thymic) large B-cell lymphoma (PMBCL);
• Transformed follicular lymphoma (TFL);
• High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBCL);
• Follicular lymphoma (FL);
• Mantle cell lymphoma (MCL) \[pathologically confirmed, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1\];
• Marginal zone lymphoma (MZL), including nodal or splenic marginal zone B-cell lymphoma and mucosa-associated lymphoid tissue (MALT) lymphoma.
• Relapse after treatment with ≥2 lines systemic therapy for all the above disease types, or refractory disease for aggressive types (DLBCL-NOS, PMBCL, TFL and HGBCL). Relapse disease is defined as disease progression after last regimen. Refractory disease is defined as no CR to first-line therapy:
• PD as best response to first-line therapy, or
• SD as best response after at least 4 cycles of first-line therapy (eg, 4 cycles of R-CHOP), or
• PR as best response after at least 6 cycles and biopsy-proven residual disease or disease progression ≤ 6 months 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.

You may not qualify if:

• No obvious hereditary diseases.
• Able to understand the requirements and matters of the trial, and willing to participate in clinical research as required.
• Informed consent must be signed.
• Patients eligible for this study must not meet any of the following criteria:
• During the screening period, there was central nervous system (CNS) invasion or a history of clinically significant central nervous system diseases, such as epilepsy and cerebrovascular diseases.
• Women who are pregnant or breastfeeding, or who do not agree to use effective contraception during treatment and during the subsequent 1 year.
• History of allogeneic hematopoietic stem cell transplantation, or organ transplantation.
• History of other malignancies that have not been in remission.
• Patients with primary immunodeficiency or autoimmune diseases requiring immunosuppressive therapy.
• Received radiotherapy within 3 months before enrollment.
• Received immunotherapy drugs within 4 weeks before enrollment, such as anti-programmed death 1 (PD-1) antibody, anti-programmed death ligand 1 (PD-L1) antibody, CD19/CD3-bispecific antibody, and so on.
• Patients who received any immunocellular therapy within 6 months before enrollment.
• Confirmed evidence showing positiveness of anti-CD19 and/or anti-CD20 scFv reactions in patient serum.
• Patients who participated in other clinical trials within 4 weeks prior to enrollment.
• Uncontrolled infectious diseases or other serious illnesses, including but not limited to infections \[e.g., human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B (HBV) or C (HCV) infection\], congestive heart failure, unstable angina, arrhythmias, or that pose an unpredictable risk in the opinion of the attending physician.

Sponsors & Collaborators

• Han weidong: lead

Study Sites (1)

Biotherapeutic Department of Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

Location

MeSH Terms

Conditions

Recurrence; Lymphoma, B-Cell

Interventions

fludarabine; fludarabine phosphate; Injections; Cyclophosphamide

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Weidong Han, M.D.

  Chinese PLA Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 20, 2020
• First Posted: January 6, 2021
• Study Start: April 15, 2021
• Primary Completion: May 31, 2025
• Study Completion (Estimated): September 1, 2026
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)