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Trial record 1 of 1 for:    NCT01593696
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Anti-CD19 White Blood Cells for Children and Young Adults With B Cell Leukemia or Lymphoma

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ClinicalTrials.gov Identifier: NCT01593696
Recruitment Status : Completed
First Posted : May 8, 2012
Results First Posted : August 31, 2020
Last Update Posted : August 31, 2020
Information provided by (Responsible Party):
Nirali N. Shah, M.D., National Cancer Institute (NCI)

Brief Summary:


- Although progress has been made in treating children with B-cell cancers such as leukemia or lymphoma, many children do not respond to the standard treatments. One possible treatment involves collecting white blood cells called T cells from the person with cancer and modifying the cells to attack the B-cell cancer. The cells can then be given back to the participant. This study will use T cells that have been modified to attack the cluster of differentiation 19 (CD19) protein, which is found on the surface of some B-cell cancers.


- To see if anti-CD19 modified white blood cells are a safe and effective treatment for children and young adults with advanced B-cell cancer.


  • Children and young adults between 1 and 30 years of age who have B-cell cancer (leukemia or lymphoma) that has not responded to standard treatments.
  • The leukemia or the lymphoma must have the CD19 protein.
  • There must be adequate organ function.


  • Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies or bone marrow biopsies may be performed depending on the type of cancer.
  • Participants will undergo a process where white blood cells are collected, called apheresis. These cells will be modified to contain the anti-CD19 gene.
  • Participants will have 3 days of chemotherapy to prepare their immune system to accept the modified cells.
  • Participants will receive an infusion of their own modified white blood cells. They will remain in the hospital until they have recovered from the treatment.
  • Participants will have frequent follow-up visits to monitor the outcome of the treatment.
  • If the participant benefits from the treatment, then he/she may have the option for another round of treatment.

Condition or disease Intervention/treatment Phase
ALL B Cell Lymphoma Leukemia Large Cell Lymphoma Non-Hodgkin Lymphoma Biological: Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR) Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 53 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of T Cells Expressing an Anti-CD19 Chimeric Receptor in Children and Young Adults With B Cell Malignancies
Actual Study Start Date : June 29, 2012
Actual Primary Completion Date : November 11, 2016
Actual Study Completion Date : October 2, 2017

Arm Intervention/treatment
Experimental: Lymphodepleting regimen of Fludarabine and Cyclophosphamide
Lymphodepleting regimen of Fludarabine and Cyclophosphamide.
Biological: Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR)
Cells extracted, followed by induction chemotherapy before Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR) infusion (dose escalation.)

Experimental: Intensive standard of care chemotherapy
Intensive standard of care chemotherapy, in lieu of the lymphodepleting chemotherapy regimen, to decrease tumor burden in preparation for the administration of the Chimeric antigen receptor (CAR) T cells.
Biological: Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR)
Cells extracted, followed by induction chemotherapy before Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR) infusion (dose escalation.)

Primary Outcome Measures :
  1. Number of Participants Who Received Preparative Chemotherapy Followed by Cluster of Differentiation (CD)19-Chimeric Antigen Receptor (CAR): CD19 CAR T-cells With < Grade 4 Cytokine Release Syndrome [ Time Frame: Beginning of preparative regimen through Day 28 after CD19 CAR infusion ]
    Participants with B cell malignancies who received preparative chemotherapy followed by CD19 CAR T-cells with < Grade 4 cytokine release syndrome.

  2. Number of Participants in Which the Prescribed Dose of Cluster of Differentiation (CD)19-Chimeric Antigen Receptor (CAR): CD19 CAR T-cells Were Successfully Manufactured [ Time Frame: Apheresis through completion of CAR manufacturing process, approximately 2 weeks ]
    Participants who had T-cells collected by apheresis and subsequently had the amount of CAR T-cells manufactured as prescribed by the dose level they were enrolled in.

Secondary Outcome Measures :
  1. Number of Participants Who Were Administered Intensive Chemotherapy Prior to Cluster of Differentiation (CD)19-Chimeric Antigen Receptor (CAR): CD19 CAR Infusion [ Time Frame: 21 days of target date ]
    Participants who were administered intensive chemotherapy prior to Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): CD19 CAR infusion and received CAR cells within 21 days of the planned infusion date.

  2. Mean Percentage Cluster of Differentiation 19 (CD19) - Chimeric Antigen-Receptor (CAR) T-Cells in Blood, Bone Marrow (BM) and Cerebrospinal Fluid (CSF) [ Time Frame: 28 days (+/- 4 days) after infusion of CD19 CAR T-cells ]
    Measure persistence of adoptively-transferred anti-CD19-CAR transduced T cells (defined by percent of CD19 CAR T-cells) in the blood and where possible the bone marrow and Cerebrospinal Fluid (CSF) of patients by flow cytometry assay.

  3. Number of Patients With a Complete Response (CR) [ Time Frame: Day 28 (+/- 4 days) after CD19 CAR infusion ]
    Complete Response (CR) was assessed by bone marrow evaluation was I defined as <5% leukemic blasts.

  4. Number of Participants With Grade 4 Cytokine Release Syndrome (CRS) [ Time Frame: Day 28 (+/- 4 days) after CD19 CAR infusion. ]
    Participants with Grade 4 Cytokine Release Syndrome (CRS). CRS is defined as a clinical syndrome that may occur after cell therapy due to the release of cytokines (substances secreted by immune cells) into the body's blood stream.

  5. Number of Participants With Serious and Non-Serious Adverse Events [ Time Frame: Date treatment consent signed to date off study, from 1.5 months up to 3.1 years. ]
    Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • Patient must have a cluster of differentiation 19 (CD19)-expressing B cell ALL or lymphoma and must have relapsed or refractory disease after at least one standard chemotherapy and one salvage regimen. In view of the principal investigator (PI) and the primary oncologist, there must be no available alternative curative therapies and subjects must be either ineligible for allogeneic stem cell transplant (SCT), have refused SCT, or have disease activity that prohibits SCT at this time.
  • CD19 expression must be detected on greater than 15% of the malignant cells by immunohistochemistry or greater than 30% by flow cytometry in a Clinical Laboratory Improvement Amendments (CLIA) approved test in the Laboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), or from the referring institution or reference laboratory. The choice of whether to use flow cytometry or immunohistochemistry will be determined by what is the most easily available tissue sample in each patient. In general immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood and bone marrow samples.
  • Patients must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis.
  • Greater than or equal to 1 year of age (and at least 15 kg) and less than or equal to 30 years of age.
  • Adequate absolute CD3 count estimated to be required to obtain target cell dose based on discussion with Department of Transfusion Medicine (DTM) apheresis and Cell Processing Section, DTM.
  • Subjects with the following central nervous system (CNS) status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy:

    • CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs;
    • CNS 2, defined as presence of < 5/uL white blood cells (WBCs) in CSF and cytospin positive for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm
    • CNS3 with marrow disease who has failed salvage systemic and intensive IT chemotherapy (and therefore not eligible for radiation)
    • Patients with isolated CNS relapse will be eligible if they have previously been treated with cranial radiation (at least centigray (cGy)).
  • Ability to give informed consent. For subjects <18 years old their legal guardian must give informed consent. Pediatric subjects will be included in age appropriate discussion and verbal assent will be obtained for those greater than or equal to 12 years of age, when appropriate.
  • Clinical performance status: Patients > 10 years of age: Karnofsky greater than or equal to 50%; Patients less than or equal to 10 years of age: Lansky scale greater than or equal to 50%. Subjects who are unable to walk because of paralysis, but who are upright in a wheelchair will be considered ambulatory for the purpose of calculating the performance score.
  • Patients of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen.
  • Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus.
  • Cardiac function: Left ventricular ejection fraction greater than or equal to 40% by multi-gated acquisition scan (MUGA) or cardiac magnetic resonance imaging (MRI), or fractional shortening greater than or equal to 28% by echocardiogram (ECHO) or left ventricular ejection fraction greater than or equal to 50% by ECHO.
  • Patients with history of allogeneic stem cell transplantation are eligible if at least 100 days post-transplant, if there is no evidence of active graft versus host disease (GVHD) and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.


Subjects meeting any of the following criteria are not eligible for participation in the study:

  • Recurrent or refractory ALL limited to isolated testicular disease.
  • Hepatic function: Inadequate liver function defined as total bilirubin > 2x upper limit of normal (ULN) (except in the case of subjects with documented Gilbert's disease > 3x ULN) or transaminase (alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 20x ULN based on age and laboratory specific normal ranges;
  • Renal function: Greater than age-adjusted normal serum creatinine (see below) and a creatinine clearance < 60 mL/min/1.73 m^2.

    • Age:

      • <= 5 yrs (Maximum Serum Creatinine = 0.8 mg/dL)
      • 5 < age <=10 yrs (Maximum Serum Creatinine =1.0 mg/dL)
      • > 10 yrs (Maximum Serum Creatinine = 1.2 mg/dL)
  • Hematologic function:

    • Absolute neutrophil count (ANC) < 750/microliter, or platelet count < 50,000/microliter, if these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy);
    • A subject will not be excluded because of pancytopenia greater than or equal to Grade 3 if it is due to disease, based on the results of bone marrow studies.
  • Hyperleukocytosis (greater than or equal to 50,000 blasts/microliter) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy;
  • Pregnant or breast-feeding females;
  • Recent prior therapy:

    • Systemic chemotherapy less than or equal to 2 weeks (6 weeks for nitrosoureas) or radiation therapy less than or equal to 3 weeks prior to apheresis;


  • There is no time restriction in regard to prior intrathecal chemotherapy provided there is complete recovery from any acute toxic effects of such;
  • Subjects receiving hydroxyurea may be enrolled provided there has been no increase in dose for at least 2 weeks prior to starting apheresis;
  • Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study provided they meet all other eligibility criteria;
  • Subjects receiving steroid therapy at physiologic replacement doses only are allowed provided there has been no increase in dose for at least 2 weeks prior to starting apheresis;
  • For radiation therapy: Radiation therapy must have been completed at least 3 weeks prior to enrollment, with the exception that there is no time restriction if the volume of bone marrow treated is less than 10% and also the subject has measurable/evaluable disease outside the radiation port.

    • Other anti-neoplastic investigational agents currently or within 30 days prior to apheresis (i.e. start of protocol therapy);
    • Subjects must have recovered from the acute side effects of their prior therapy, such that eligibility criteria are met. Cytopenias deemed to be disease-related and not therapy-related are exempt from this exclusion.

      • Human immunodeficiency virus/hepatitis B virus/Hepatitis C virus (HIV/HBV/HCV) Infection:
  • Seropositive for HIV antibody. (Patients with HIV are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy in the future should study results indicate effectiveness.)
  • Seropositive for hepatitis C or positive for Hepatitis B surface antigen (HbsAG).

    • Monoclonal antibody therapy administered within 30 days of the agent prior to apheresis;
    • Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the principal investigator (PI) would pose an unacceptable risk to the subject;
    • Second malignancy other than in situ carcinoma of the cervix, unless the tumor was treated with curative intent at least two years previously and subject is in remission;
    • History of severe, immediate hypersensitivity reaction attributed to compounds of similar chemical or biologic composition to any agents used in study or in the manufacturing of the cells (i.e. gentamicin);

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): NCT01593696

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Nirali N Shah, M.D. National Cancer Institute (NCI)
  Study Documents (Full-Text)

Documents provided by Nirali N. Shah, M.D., National Cancer Institute (NCI):
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Nirali N. Shah, M.D., Principal Investigator, National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01593696    
Other Study ID Numbers: 120112
First Posted: May 8, 2012    Key Record Dates
Results First Posted: August 31, 2020
Last Update Posted: August 31, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nirali N. Shah, M.D., National Cancer Institute (NCI):
CD 19 Expressing B Cells
B Cell Lymphoma
Anti-CD19 Chimeric Antigen Receptor
Adoptive Immunotherapy
Additional relevant MeSH terms:
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Lymphoma, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin