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Safety and Efficacy of iPD1 CD19 eCAR T Cells in Relapsed or Refractory B-cell Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03208556
Recruitment Status : Unknown
Verified July 2017 by Jun Zhu, Peking University.
Recruitment status was:  Recruiting
First Posted : July 5, 2017
Last Update Posted : September 14, 2017
Sponsor:
Collaborator:
Marino Biotechnology Co., Ltd.
Information provided by (Responsible Party):
Jun Zhu, Peking University

Brief Summary:

PD1 pathway is critical in determining the response to CAR T cell therapy. Emerging data suggested that Inhibition of PD1 could enhance the efficacy of CAR T cell therapy. iPD1 CD19 eCAR T cells is an enhanced version of the classical 2nd generation anti-CD19 4-1BB-costimulatory chimeric antigen receptor engineered T cells with cell-intrinsic PD1 inhibition by incorporation of a PD1 shRNA-expressing cassette in the CAR lentivector. This design will enhance the anti-tumor activities of CAR T cells by inhibiting PD1 induction after CAR T cell activation. This pilot, single arm, one center, dose-escalation, open label study is to determine the safety and efficacy of iPD1 CD19 eCAR T cells in relapsed or refractory CD19 positive lymphoma.

Subjects will be given a lymphodepletion chemotherapy comprised of Fludarabine and cyclophosphamide prior to CAR T cell infusion. The chemotherapy is completed 1 to 4 days before the first dost of iPD1 CD19 eCAR T cells.


Condition or disease Intervention/treatment Phase
Relapsed or Refractory B-cell Lymphoma Biological: iPD1 CD19 eCAR T cells Drug: Fludarabine and cyclophosphamide Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Autologous Anti-CD19 4-1BB CAR T Cells With Cell-intrinsic PD1 Inhibition in Relapsed or Refractory B-cell Lymphoma
Actual Study Start Date : June 21, 2017
Estimated Primary Completion Date : June 1, 2019
Estimated Study Completion Date : June 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Fludarabine

Arm Intervention/treatment
Experimental: iPD1 CD19 eCAR T cells
patients will receive a lymphodepletion chemotherapy prior to CAR T cell infusion
Biological: iPD1 CD19 eCAR T cells

iPD1 CD19 eCAR T cells are administrated in a 3-day split-dose regimen (d0, 30%; d1, 30%; d2, 40%).

CAR T cell dose escalation: 1×10^5 /kg,1×10^6 /kg,3×10^6 /kg,and 6×10^6 CAR T cells/kg


Drug: Fludarabine and cyclophosphamide
Fludarabine 25 mg/m2 d1-3; cyclophosphamide 250 mg/m2 d1-3. Lymphodepletion chemotherapy is completed 1 to 4 days before CAR T cell infusion




Primary Outcome Measures :
  1. safety of infusion of iPD1 CD19 eCAR T cells as assessed by the incidents of treatment related adverse events per NCI CTCAE V4.0 [ Time Frame: 2 years ]
    incidents of treatment related adverse events per NCI CTCAE V4.0


Secondary Outcome Measures :
  1. treatment response [ Time Frame: 6 months ]
    The efficacy of infusion of iPD1 CD19 eCAR T cells is assessed according to the standardized response criteria for malignant lymphoma (Cheson BD, JCO, 2007), which is defined as complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD).

  2. overall survival [ Time Frame: 3 years ]
    Overall survival is defined as the time from receiving iPD1 CD19 eCAR T cells infusion to death for any cause.

  3. progression-free survival [ Time Frame: 2 years ]
    Progression-free survival (PFS) is defined as the time from receiving iPD1 CD19 eCAR T cell infusion to disease progression or death from any cause.


Other Outcome Measures:
  1. Persistence of iPD1 CD19 eCAR T cells in patients [ Time Frame: 2 years ]
    measured by quantitative PCR

  2. proliferation of iPD1 CD19 eCAR T cells in patients [ Time Frame: 6 months ]
    measured by flow cytometry



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. CD19+ B cell lymphoma,verified by IHC or flow cytometry.
  2. a prior history of at least one standard care of medication.
  3. ineligible for allogeneic transplantation or relapsed after transplantation.
  4. patients are 18 years older.
  5. life expectancy > 3months.
  6. ECOG ≤ 2.
  7. satisfactory major organ functions: adequate heart function with LVEF≥50%; pulse oximetry of ≥ 90%; cockcroft-gault creatinine clearance≥40 ml/min; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3ULN; Bilirubin ≤2.0 mg/dl .
  8. Blood: Hgb ≥ 80 g/L, ANC ≥ 1×10^9/L, PLT ≥ 50×10^9/L.
  9. women of reproductive potential must have a negative pregnancy test. Male and female of reproductive potential must agree to use birth control during the study and one year post study.
  10. measurable tumors.

Exclusion Criteria:

  1. using immunosuppressive drugs or systemic steroids within one week of enrollment.
  2. active infection.
  3. HIV positive.
  4. active hepatitis B virus infection or hepatitis C virus infection.
  5. breastfeeding or pregnant women.
  6. patients refuse to practice birth control during study and one year post study.
  7. patients with a prior history of other malignances will be excluded from this study, but patients who have been cured from skin basal cell carcinoma or cervical cancer, or who have had their tumors removed by surgical resection but without further therapies and have more than 5 years of progression-free survival, can be included into the study.
  8. currently enrolled in other study.
  9. patients, in the opinion of investigators, may not be eligible or are not able to comply with the study.

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): NCT03208556


Contacts
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Contact: Jun Zhu, MD +86-10-88196596 zj@bjcancer.org
Contact: Zhitao Ying, MD yingzhitao001@163.com

Locations
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China
Beijing Cancer Hosptical Recruiting
Beijing, China
Contact: Zhitao Ying, MD       yingzhitao001@163.com   
Principal Investigator: Jun Zhu, MD         
Sub-Investigator: Zhitao Ying, MD         
Sub-Investigator: Xiaoyu Xiang, PhD         
Sponsors and Collaborators
Peking University
Marino Biotechnology Co., Ltd.
Investigators
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Principal Investigator: Jun Zhu, MD Beijing Cancer Hospital
Study Director: Zhitao Ying, MD Beijing Cancer Hospital
Study Director: Xiaoyu Xiang, PhD Marino Biotechnology Co., Ltd.
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Responsible Party: Jun Zhu, Professor, Peking University
ClinicalTrials.gov Identifier: NCT03208556    
Other Study ID Numbers: 2017YJZ13
First Posted: July 5, 2017    Key Record Dates
Last Update Posted: September 14, 2017
Last Verified: July 2017

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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
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists