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Protocol Details

Phase I Study of T Cells Expressing an Anti-CD19 Chimeric Receptor in Children and Young Adults with B Cell Malignancies

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 1 Years
Max Age: 30 Years

Referral Letter Required


Population Exclusion(s)



CD 19 Expressing B Cells;
B Cell Lymphoma;
Anti-CD19 Chimeric Antigen Receptor;
Adoptive Immunotherapy

Recruitment Keyword(s)



B Cell Lymphoma;
Large Cell Lymphoma;
Non-Hodgkin Lymphoma

Investigational Drug(s)

Autologous peripheral blood lymphocytes cultured with OKT3 and Interleukin2
Transduced with retroviral vector expressing Anti-CD19 chimeric antigen gene

Investigational Device(s)



Biological/Vaccine: Anti-CD19-CAR

Supporting Site

National Cancer Institute


- 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 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.

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-Patient must have a 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 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 CLIA approved test in the Laboratory of Pathology, CCR, NCI, 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 DTM apheresis and Cell Processing Section, DTM.

-Subjects with the following 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 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 1800 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 MUGA or cardiac MRI, or fractional shortening greater than or equal to 28% by 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 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 (ALT and 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.


--- <= 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.

-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 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).

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Kowolik CM, Topp MS, Gonzalez S, Pfeiffer T, Olivares S, Gonzalez N, Smith DD, Forman SJ, Jensen MC, Cooper LJ. CD28 costimulation provided through a CD19-specific chimeric antigen receptor enhances in vivo persistence and antitumor efficacy of adoptively transferred T cells. Cancer Res. 2006 Nov 15;66(22):10995-1004.

Kochenderfer JN, Wilson WH, Janik JE, Dudley ME, Stetler-Stevenson M, Feldman SA, Maric I, Raffeld M, Nathan DA, Lanier BJ, Morgan RA, Rosenberg SA. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood. 2010 Nov 18;116(20):4099-102. doi: 10.1182/blood-2010-04-281931. Epub 2010 Jul 28.

Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther. 2010 Apr;18(4):843-51. doi: 10.1038/mt.2010.24. Epub 2010 Feb 23.

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Principal Investigator

Referral Contact

For more information:

Nirali N. Shah, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 1-5750
(240) 760-6970

Bonnie D. Yates, C.R.N.P.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 1-5750
(240) 760-6204

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


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