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Trial record 16 of 34 for:    Han weidong

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

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ClinicalTrials.gov Identifier: NCT03097770
Recruitment Status : Recruiting
First Posted : March 31, 2017
Last Update Posted : September 10, 2019
Sponsor:
Information provided by (Responsible Party):
Han weidong, Chinese PLA General Hospital

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Hematopoietic/Lymphoid Cancer Adult Acute Lymphoblastic Leukemia in Remission B-cell Adult Acute Lymphoblastic Leukemia B-cell Chronic Lymphocytic Leukemia Prolymphocytic Leukemia Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Refractory Chronic Lymphocytic Leukemia Stage III Adult Diffuse Large Cell Lymphoma Stage III Chronic Lymphocytic Leukemia Stage III Grade 1 Follicular Lymphoma Stage III Grade 2 Follicular Lymphoma Stage III Grade 3 Follicular Lymphoma Stage III Mantle Cell Lymphoma Stage IV Adult Diffuse Large Cell Lymphoma Stage IV Chronic Lymphocytic Leukemia Stage IV Grade 1 Follicular Lymphoma Stage IV Grade 2 Follicular Lymphoma Stage IV Grade 3 Follicular Lymphoma Stage IV Mantle Cell Lymphoma Biological: anti-CD19/20-CAR vector-transduced T cells Not Applicable

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD19/CD20 vector (referred to as tanCART-19/20 cells).

II. Determine duration of in vivo survival of tanCART-19/20 cells. RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of tanCART-19/20 TCR (T-cell receptor) zeta:CD137 and TCR zeta cells over time.

SECONDARY OBJECTIVES:

I. For patients with detectable disease, measure anti-tumor response due to tanCART-19/20 cell infusions.

II. To determine if the CD137 transgene is superior to the TCR zeta only transgene as measured by the relative engraftment levels of tanCART-19/20 TCR zeta:CD137 and TCR zeta cells over time.

III. Estimate relative trafficking of tanCART-19/20 cells to tumor in bone marrow and lymph nodes.

IV. For patients with stored or accessible tumor cells (such as patients with active chronic lymphocytic leukemia(CLL), acute lymphocytic leukemia (ALL), etc) determine tumor cell killing by tanCART-19/20 cells in vitro.

V. Determine if cellular or humoral host immunity develops against the murine anti-CD19/20, and assess correlation with loss of detectable tanCART-19/20 (loss of engraftment).

VI. Determine the relative subsets of tanCART-19/20 T cells (Tcm, Tem, and Treg).

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 days 0,1, and 2 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 13 years.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Clinical Study of CD19/CD20 tanCAR T Cells in Relapsed and/or Chemotherapy Refractory B-cell Leukemias and Lymphomas
Actual Study Start Date : April 1, 2017
Actual Primary Completion Date : May 10, 2019
Estimated Study Completion Date : April 1, 2020


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 days 0,1, 2 in the absence of disease progression or unacceptable toxicity.
Biological: anti-CD19/20-CAR vector-transduced T cells
genetically engineered lymphocyte therapy
Other Name: genetically engineered lymphocyte therapy




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Anti-tumor responses to tanCART19/20 cell infusions [ Time Frame: up to 24 weeks ]

Other Outcome Measures:
  1. in vivo existence of tanCART19/20 [ Time Frame: 1 year ]


Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

  1. Age ≥16 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. Primary 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. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03097770


Contacts
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Contact: weidong han, Dr 86-10-66937463 hanwdrsw@sina.com

Locations
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China, Beijing
Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital Recruiting
Beijing, Beijing, China, 100853
Contact: weidong han, Dr    86-10-66937463    hanwdrsw@sina.com   
Sponsors and Collaborators
Chinese PLA General Hospital

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Responsible Party: Han weidong, PI, Chinese PLA General Hospital
ClinicalTrials.gov Identifier: NCT03097770     History of Changes
Other Study ID Numbers: CHN-PLAGH-BT-020
First Posted: March 31, 2017    Key Record Dates
Last Update Posted: September 10, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Leukemia, Prolymphocytic
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Lymphoma, B-Cell