Anti-CD19 White Blood Cells for Children and Young Adults With B Cell Leukemia or Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01593696
First received: May 5, 2012
Last updated: July 22, 2014
Last verified: March 2014
  Purpose

Background:

- 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.

Objectives:

- 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.

Eligibility:

  • 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.

Design:

  • 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 Intervention Phase
ALL
B Cell Lymphoma
Leukemia
Large Cell Lymphoma
Non-Hodgkin Lymphoma
Biological: Anti-CD19- CAR
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Safety & amp; Feasibility [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Persistence of Anti-CD19-CAR Tcells [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Antitumor Effects [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: April 2012
Estimated Study Completion Date: January 2020
Estimated Primary Completion Date: January 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
prior allogeneic SCT
Biological: Anti-CD19- CAR
Cells extracted, followed by induction chemotherapy before CD19-CAR infusion (dose escalation.)
Experimental: 2
no SCT
Biological: Anti-CD19- CAR
Cells extracted, followed by induction chemotherapy before CD19-CAR infusion (dose escalation.)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    • 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. 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.
    • 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

        • CNS 2a: < 10/uL RBCs; < 5/uL WBCs and cytospin positive for blasts;
        • CNS 2b: greater than or equal to10/uL RBCs; < 5/uL WBCs and cytospin positive for blasts;
        • CNS 2c: greater than or equal to 10/uL RBCs; greater than or equal to 5/uL WBCs and cytospin positive for blasts but negative by Steinherz/Bleyer algorithm.
    • 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 greater than or equal to 40% by MUGA, 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.

EXCLUSION CRITERIA:

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

  • Recurrent or refractory ALL limited to isolated testicular or isolated central nervous system (CNS) disease.
  • Hepatic function: Inadequate liver function defined as total bilirubin > 2x upper limit of normal (ULN) (except in the case of subjects with documented Gilberts disease > 3x ULN) or transaminase (ALT and AST) > 5x ULN based on age- and laboratory specific normal ranges;
  • Renal function: Greater than age-adjusted normal serum creatinine (see Table below) and a creatinine clearance < 60 mL/min/1.73 m(2).

    • Age (Years) - greater than or equal to 5 - Maximum Serum Creatinine (mg/dL) - 0.8
    • Age (Years) 5 less than or equal to 10 - Maximum Serum Creatinine (mg/dL) 1.0
    • Age (Years) - greater than 10- Maximum Serum Creatinine (mg/dL) 1.2
  • Hematologic function:

    • Absolute neutrophil count (ANC) < 750/microL, or platelet count < 50,000/microL, 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.
  • Subjects with radiologically-detected CNS lymphoma or CNS 3 disease (presence

of greater than or equal to 5/(Mu)L WBCs in CSF and cytospin positive for blasts [in the absence of a traumatic lumbar puncture] and/or clinical signs of CNS leukemia);

  • Hyperleukocytosis (greater than or equal to 50,000 blasts/?L) 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 to3 weeks prior to apheresis;

      • Exceptions:

        • 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 5 half-lives 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).
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01593696

Contacts
Contact: Cindy P Delbrook, R.N. (301) 496-9454 delbrookc@mail.nih.gov
Contact: Daniel W Lee, M.D. (301) 435-6236 leed3@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    (888) NCI-1937      
Sponsors and Collaborators
Investigators
Principal Investigator: Daniel W Lee, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01593696     History of Changes
Other Study ID Numbers: 120112, 12-C-0112
Study First Received: May 5, 2012
Last Updated: July 22, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
CD 19 Expressing B Cells
B Cell Lymphoma
ALL
Anti-CD19 Chimeric Antigen Receptor
Adoptive Immunotherapy

Additional relevant MeSH terms:
Leukemia
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 29, 2014