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Competitive Transfer of αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T Cells for B-cell Leukemia/Lymphoma (MatchCART)

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ClinicalTrials.gov Identifier: NCT02685670
Recruitment Status : Unknown
Verified March 2017 by Chengzhi, The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine.
Recruitment status was:  Recruiting
First Posted : February 19, 2016
Last Update Posted : March 16, 2017
Sponsor:
Collaborators:
Xinqiao Hospital of Chongqing
Xuzhou Medical University
Information provided by (Responsible Party):
Chengzhi, The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine

Brief Summary:
This is a single-arm open-label phase I/II study to determine the relative superiority of αCD19-TCRζ-CD28 and αCD19-TCRζ-CD137 CAR-T Cells in safety, efficacy and engraftment potential in patients with CD19+ B-lineage leukemia and lymphoma. Recently, cancer immunotherapy, treatments aiming to arm patients with immunity specifically against cancer cells, has emerged as a promising therapeutic strategy. Clinical trials utilizing CARs against B cell malignancies have demonstrated remarkable potential. In this trial, all subjects will be competitively infused with αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T cells in equal number to test a hypothesis that CD137-costimulation can promote the persistence and engraftment of CAR-T cells and this superiority can lead to improved progression-free survival.

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 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 CAR-T Drug: Fludarabine Drug: Cyclophosphamide Phase 1 Phase 2

Detailed Description:

Primary objectives

1. To determine the safety and feasibility of adoptive transfer of T cells modified to express CD19-specific chimeric antigen receptor (CD19CAR) for treatment of leukemia and lymphoma

Secondary objectives

  1. To measure the efficacy of anti-tumor responses after CD19CAR T cell infusion
  2. To determine if CD19CAR T cells engineered with 4-1BB signaling domain is superior to that with CD28 signaling domain for their homing and persistence after CD19CAR T cell infusion

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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: A Phase I/II Study of Competitive Transfer of αCD19-TCRz-CD28 and αCD19-TCRz-CD137 Chimeric Antigen Receptor T-Cells in Patients With Refractory CD19+ B-lineage Leukemia/Lymphoma
Study Start Date : February 2016
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
Experimental: Mixed CD19CAR transfer
All subjects will be infused with αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T cells in equal number
Biological: anti-CD19 CAR-T
Ex vivo-expanded autologous T cells modified to express CD19 CAR

Drug: Fludarabine
Drug: Cyclophosphamide



Primary Outcome Measures :
  1. Safety (incidence of adverse events defined as dose-limited toxicity) [ Time Frame: 30 days ]

Secondary Outcome Measures :
  1. Overall complete remission rate [ Time Frame: 8 weeks ]
  2. Survival of CAR T cells in circulation measured by flow cytometry and PCR [ Time Frame: 1 year ]
  3. Duration of remission [ Time Frame: 1 year ]
  4. Overall survival [ Time Frame: 1 year ]


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Ages Eligible for Study:   5 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 5 Years to 70 Years, Male and female;
  2. Expected survival > 12 weeks;
  3. Performance score 0-2;
  4. Histologically confirmed as CD19-positive lymphoma/leukemia and who meet one of the following conditions;

    • Patient receive at least 2-4 prior combination chemotherapy regimens (not including single agent monoclonal antibody therapy) and fail to achieve CR; or have disease recurrence; or not eligible for allogeneic stem cell transplantation; or disease responding or stable after most recent therapy but refused further treatment;
    • Disease recurrence after stem cell transplantation;
    • Diagnosis as lymphoma, but refuse conventional treatment such as chemotherapy, radiation, stem cell transplantation and monoclonal antibody therapy
  5. Creatinine < 2.5 mg/dl;
  6. ALT/AST < 3x normal;
  7. Bilirubin < 2.0 mg/dl;
  8. Adequate venous access for apheresis, and no other contraindications for leukapheresis;
  9. Take contraceptive measures before recruit to this trial;
  10. Written voluntary informed consent is given.

Exclusion Criteria:

  1. Patients with symptoms of central nervous system
  2. Accompanied by other malignant tumor
  3. Active hepatitis B or C, HIV infection
  4. Any other diseases could affect the outcome of this trial
  5. Suffering severe cardiovascular or respiratory disease
  6. Poorly controlled hypertension
  7. A history of mental illness and poorly controlled
  8. Taking immunosuppressive agents within 1 week due to organ transplantation or other disease which need long-lasting administration
  9. Occurrence of unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events 30 days prior to assignment
  10. Reaching a steady dose if receiving anticoagulant therapy before assignment
  11. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
  12. Pregnant or lactating women
  13. Subject suffering disease affects the understanding of informed consent or comply with study protocol.

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): NCT02685670


Contacts
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Contact: Zhi Cheng, M.D. +(86)-139-3852-6995 clinicaltrials.chengzhi@outlook.com

Locations
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China, Henan
Henan Province of TCM Recruiting
Zhengzhou, Henan, China
Contact: Zhi Cheng, M.D.         
Sponsors and Collaborators
The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine
Xinqiao Hospital of Chongqing
Xuzhou Medical University
Investigators
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Principal Investigator: Zhi Cheng, M.D. The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine

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Responsible Party: Chengzhi, Director of Department of Hematology, The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine
ClinicalTrials.gov Identifier: NCT02685670    
Other Study ID Numbers: DHHUTCM20160106
First Posted: February 19, 2016    Key Record Dates
Last Update Posted: March 16, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Lymphoma, B-Cell
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