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

Sponsor
Han weidong (Other)
Overall Status
Recruiting
CT.gov ID
NCT04697940
Collaborator
(none)
30
1
1
60.5
0.5

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: Decitabine-primed Tandem CAR19/20 engineered T cells
Phase 1/Phase 2

Detailed Description

Phase I dose escalation (3+3) : dose 1 (0.5 × 106 cells per kg) dose 2 (2 × 106 cells per kg) dose 3 (5 × 10^6 cells per kg)

Phase II Appropriate dose

Study Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Decitabine-primed Tandem Targeting CD19 and CD20 Chimeric Antigen Receptor T Cells Treatment in Relapsed and/or Refractory Non-Hodgkin's Lymphoma Patients
Actual Study Start Date :
Dec 15, 2020
Anticipated Primary Completion Date :
Dec 30, 2023
Anticipated Study Completion Date :
Dec 30, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Refractory or Relapsed Non-Hodgkin's Lymphoma

Decitabine-primed Tandem CAR19/20 engineered T cells

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

Outcome Measures

Primary Outcome Measures

  1. Safety in phase I [3 month]

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

  2. Best objective Response Rate [12 month]

    the incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as best response to treatment

Secondary Outcome Measures

  1. Progression Free Survival [12 month]

    PFS is defined as the time from the CAR T cells infusion date to the date of disease progression or death any cause.

  2. Duration of Response [12 month]

    DOR for subjects who experience an objective response, DOR is defined as the date of their first objective response (which is subsequently confirmed) to disease progression for r/r B-NHL or death regardless of cause.

  3. Overall Survival [24 month]

    OS is defined as the time from CAR T cells infusion to the date of death. Subjects who have not died by the analysis data cutoff date will be censored at their last contact date.

Other Outcome Measures

  1. Exploratory research:Track CAR T cells in patients after infusion using TCR, transcriptional, and epigenetic sequencing. [14-28 days after infusion]

    Analysis of CAR T cell populations from patients using single-cell sequencing to distinct subtypes and clonal expansion of infiltrating lymphocytes. By means of the transcriptional profiles of these individual cells, coupled with assembled T cell receptor (TCR) sequences to identify CAR T cell subsets based on their molecular and functional properties.

Eligibility Criteria

Criteria

Ages Eligible for Study:
16 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
Patients eligible for inclusion in this study had to meet all of the following criteria:
  • Age ≥16 and ≤70 years.

  • Eastern Cooperative Oncology Group (ECOG) performance status score between 0 and 2.

  • Histologically confirmed CD20+ and/or CD19+ B-cell non-Hodgkin lymphoma (NHL), including the following types defined by the World Health Organization (WHO) 2008: Diffuse large B-cell lymphoma (DLBCL) not otherwise specified, Primary mediastinal large B-cell lymphoma (PMBCL), Transformed follicular lymphoma (tFL), FL, Some indolent lymphomas including mantle-cell lymphoma (MCL) and chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), Mucosa associated lymphoid tissue (MALT), Others.

  • 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.

  • 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.

Exclusion Criteria:
Patients eligible for this study must not meet any of the following criteria:
  • 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 <45%.

  • History of allogeneic stem cell transplantation.

  • Requirement for urgent therapy due to tumor 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 tumor requiring therapy or intervention.

  • 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Biotherapeutic Department of Chinese PLA General Hospital Beijing Beijing China 100853

Sponsors and Collaborators

  • Han weidong

Investigators

  • Principal Investigator: Weidong Han, M.D., Chinese PLA Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Han weidong, Professor, Chinese PLA General Hospital
ClinicalTrials.gov Identifier:
NCT04697940
Other Study ID Numbers:
  • CHN-PLAGH-BT-058
First Posted:
Jan 6, 2021
Last Update Posted:
Mar 28, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 28, 2022