Treatment of Relapsed and/or Chemotherapy Refractory B-cell Malignancy by Tandem CAR T Cells Targeting CD19 and CD20

August 31, 2020 updated by: Han weidong, Chinese PLA General Hospital

Clinical Study of CD19/CD20 tanCAR T Cells in Relapsed and/or Chemotherapy Refractory B-cell Leukemias and Lymphomas

RATIONALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells.

PURPOSE: This clinical trial is studying genetically engineered lymphocyte therapy in treating patients with B-cell leukemia or lymphoma that is relapsed (after stem cell transplantation or intensive chemotherapy) or refractory to chemotherapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

To assess the efficacy of TanCAR19/20 T cells in relapsed or refractory NHL, defined as overall response rate (ORR).

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability of TanCAR19/20 T cells. II. To evaluate time to response (TTR), duration of overall response (DOR), progression free survival (PFS) and overall survival (OS).

III. To determine in vivo expansion and persistence of TanCAR19/20 T cells.

OUTLINE: Patients are assigned to 1 group according to order of enrollment. Patients receive anti-CD19/20-CAR (coupled with CD137 and CD3 zeta signalling domains)vector-transduced autologous T cells on day1 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed intensively for 6 months, every 3 months for 2 years, and annually thereafter for 3 years.

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100853
        • Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Patients eligible for inclusion in this study have to meet all of the following criteria:

  1. Age ≥18 and ≤70 years.
  2. Performance status (ECOG) between 0 and 2.

  3. Histologically confirmed CD20+ and/or CD19+ B-cell non-Hodgkin lymphoma (NHL), including the following types defined by WHO 2008:

    • DLBCL not otherwise specified, DLBCL associated with chronic inflammation, and Epstein-Barr virus (EBV)+ DLBCL in the elderly.
    • Primary mediastinal (thymic) large B-cell lymphoma (PMBCL). The mediastinal mass had to have an axial diameter <5 cm or extranodal lesion size <3 cm. Patients with large lesions (≥5 cm) were enrolled in our other clinical trial (NCT0334662).
    • Transformed FL (tFL) .
    • FL.
    • Some indolent lymphomas including MCL and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

  4. Refractory disease or relapsed after treatment with ≥2 lines of chemotherapy including rituximab and anthracycline and either having failed autologous HSCT or being ineligible for 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.
    • 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 a 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 ASCT (requires biopsy-proven recurrence in relapsed subjects).
    • No response or relapse after salvage therapy is given post-ASCT.
  5. PD or relapse ≥3 months after treatment with a targeted CD19 therapy, including CD19-CAR T cells or anti-CD19/anti-CD3.
  6. Successful leukapheresis assessment and pre-culture of T cells.
  7. Life expectancy > 3 months.

  8. Adequate organ function:

    • Creatinine < 1.6 mg/dL (140 µmol/L) or creatinine clearance ≥60 mL/min.
    • ALT/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. No clinically significant pleural effusion.
    • Cardiac ejection fraction ≥50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings.

  9. 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.
  10. Measurable or assessable disease according to the "IWG Response Criteria for Malignant Lymphoma" (Cheson 2007). Patients in CR with no evidence of disease were not eligible.
  11. 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:

  1. Patients with definite involvement of gastrointestinal tract. Endoscopy should be performed to conform gastrointestinal involvement for patients suspected. However, patients with central nervous system (CNS) involvement were cautiously enrolled in this clinical study.
  2. CD19 CAR T cell treatment failure or recurrence, detection of a clear HAMA effect, or negative tumour puncture detection of CD19 and CD20.
  3. Pregnant or lactating women.
  4. Uncontrolled active bacterial or viral infection. (active hepatitis B or hepatitis C infection, HIV infection) or treponema pallidum infection.
  5. Class III/IV cardiovascular disability according to the New York Heart Association Classification and a cardiac ejection fraction ≥50%.
  6. History of allogeneic stem cell transplantation.
  7. Any autoimmune disease or primary immunodeficiency.
  8. Requirement for urgent therapy due to tumour mass effects such as respiratory obstruction or blood vessel compression.
  9. Current or expected need for systemic corticosteroid therapy.
  10. Any organ failure.
  11. The patients with the second tumour requiring for therapy or intervention.
  12. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: anti-CD19/20 CAR T cells
Patients receive anti-CD19/20-CAR retroviral vector-transduced autologous or donor-derived T cells on day 1 in the absence of disease progression or unacceptable toxicity.
Biological: anti-CD19/20-CAR vector-transduced T cells
genetically engineered lymphocyte therapy
Other Names:
  • genetically engineered lymphocyte therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurrence of study related adverse events
Time Frame: Until week 24
defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment
Until week 24

Secondary Outcome Measures

Outcome Measure
Time Frame
Anti-tumor responses to tanCART19/20 cell infusions
Time Frame: up to 96 weeks
up to 96 weeks

Other Outcome Measures

Outcome Measure
Time Frame
In vivo existence of TanCART19/20
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chinese PLA General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2017

Primary Completion (Actual)

May 10, 2019

Study Completion (Actual)

January 31, 2020

Study Registration Dates

First Submitted

March 26, 2017

First Submitted That Met QC Criteria

March 26, 2017

First Posted (Actual)

March 31, 2017

Study Record Updates

Last Update Posted (Actual)

September 2, 2020

Last Update Submitted That Met QC Criteria

August 31, 2020

Last Verified

December 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHN-PLAGH-BT-020

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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