Phase I/IIA Study of CART19 Cells for Patients With Chemotherapy Resistant or Refractory CD19+ Leukemia and Lymphoma (Pedi CART19)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2016 by University of Pennsylvania
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01626495
First received: June 18, 2012
Last updated: January 19, 2016
Last verified: January 2016
  Purpose

This is a study for children who have been previously treated for Leukemia/Lymphoma. In particular, it is a study for people who have a type of Leukemia/Lymphoma that involves B cells (a type of white cell), which contain the cancer. This is a new approach for treatment of Leukemia/Lymphoma that involves B cells (tumor cells). This study will take the subject's white blood cells (T cells) and modify them in order to target the cancer.

The subject's T cells will be modified in one or two different ways that will allow the cells to identify and kill the tumor cells (B cells). Both ways of modifying the cells tells the T cells to go to the B cells (tumor cells) and turn "on" and potentially kill the B cells (tumor cells). The modification is a genetic change to the T cells, or gene transfer, in order to allow the modified T cells to recognize your tumor cells but not other normal cells in the subject's body. These modified cells are called chimeric antigen receptor 19 (CART19) T-cells.


Condition Intervention Phase
B Cell Leukemia
B Cell Lymphoma
Biological: CART-19
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: CHP 959 - A Phase I/IIA Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCRzeta and 4-1BB Signaling Domains in Patients With Chemotherapy Resistant Or Refractory CD19+ Leukemia and Lymphoma

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Safety of CAR+ T cell infusion and observed side effects


Secondary Outcome Measures:
  • Ability of two different types of CAR+ T cells to expand and persist in the patient [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    The change in the ratio of the vector transduced cells to each other between baseline and week four will be evaluated. Observation and monitoring of patients will continue on a monthly basis until week 24 post dosing

  • Impact of CAR+ T cell infusion on cancer [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Patients with measurable disease will be assessed for the response of their disease to the CAR+ T cell treatment


Estimated Enrollment: 20
Study Start Date: August 2011
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CART-19 T Cells
The subject's thawed T cells will be modified in one or two different ways that will allow the cells to identify and kill the tumor cells (B cells). The T cells will be infused over 10-15 minutes on days Days 0, and 1. Day 14 is tentative based on response.
Biological: CART-19
Day 0: 10% of total dose Day 1: 30% of total dose if patient is stable (no significant toxicity) from prior dose.

Detailed Description:

At entry subjects will be staged and the suitability of their T cells for CART-19 manufacturing will be determined. Subjects who have adequate T cells will be leukapheresed to obtain large numbers of peripheral blood mononuclear cells (PBMC) for CART-19 manufacturing. The T cells will be purified from the PBMC, transduced with CART-19 lentiviral vector, expanded in vitro and then frozen for future administration. Chemotherapy will then be given. Following tumor burden reassessment, CART-19 cells will be thawed and infused.

Subjects will have blood tests to assess safety, and engraftment and persistence of the CART-19 cells at regular intervals through four weeks after their last infusion of the study. Following the 6 months of intensive follow-up, subjects will be evaluated quarterly for two years with a medical history, a physical examination, and blood tests. Following this evaluation, subjects will enter a roll-over study for annual follow-up by phone and questionnaire for an additional thirteen years to assess for the diagnosis of long-term health problems, such as development of new malignancy.

Primary objectives:

  1. Determine the safety and feasibility of administration of chimeric antigen receptor T cells transduced with the anti-CD 19 lentiviral vector (referred to as "CART-19" cells).
  2. Determine duration of in vivio survival of CART-19 cells. Real Time polymerase chain receptor (RT-PCR) analysis of whole blood will be used to detect and quantify survival of CART-19 TCR:4-1BB and TCR cells over time.

Secondary objectives:

  1. For patients with detectable disease, measure anti-tumor response due to CART-19 cell infusions.
  2. To determine if the 4-1BB transgene is superior to the TCR only transgene as measured by the relative engraftment levels of CART-19 TCR:4-1BB and TCR cells over time.
  3. For patients with stored or accessible tumor cells (such as patients with active chronic lymphocytic leukemia (CLL), acute lymphoblastic leukema (ALL), etc) determine tumor cell killing by CART-19 cells in vitro.
  4. Determine if cellular or humoral host immunity develops against the murine anti-CD19, and assess correlation with loss of detectable CART-19 (loss of engraftment).
  5. Determine the relative subsets of CART-19 T cells (Tcm, Tem, and Treg)
  Eligibility

Ages Eligible for Study:   1 Year to 24 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Male and female subjects with CD19+ B cell malignancies in patients with no available curative treatment options (such as autologous or allogeneic SCT) who have limited prognosis (several months to <2 year survival) with currently available therapies will be enrolled:

  1. Eligible diseases: CD19+ leukemia or lymphoma

    a. ALL without curative options for therapy, including those not eligible for allogeneic SCT because of: i. age ii. comorbid disease iii. other contraindications to TBI-based conditioning (required for ALL SCT) iv. lack of suitable donor v. prior SCT vi. Declines allo SCT (in CR3) as a therapeutic option after documented discussion about the role of SCT with a BMT physician not part of the study team

    . Patient may be in any complete response, or patient may have active disease but responding or stable after most recent therapy. The intent is not to enroll patients with no degree of disease control, or rapidly increasing disease burden between enrollment and cell infusion.

    b. Diffuse large cell lymphoma or other high-grade NHL, previously identified as CD19+ i. Residual disease after primary therapy and not eligible for autologous SCT. ii. Relapsed after prior autologous SCT. iii. Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT.

  2. Age 1 to 24 years. Patients ages 22-24 will only be enrolled if they are currently being treated at CHOP or another pediatric facility/oncologist.
  3. Expected survival > 12 weeks
  4. Creatinine < 2.5 mg/dl and less than 2.5x normal for age
  5. ALT <= 5x normal
  6. Bilirubin <2.0 mg/dl
  7. Any relapse after prior SCT will make patient eligible regardless of other prior therapy.
  8. Patients with relapsed disease after prior allogeneic SCT (myeloablative or non-myeloablative) will be eligible if they meet all other inclusion criteria and

    1. Have no active GVHD and require no immunosuppression
    2. Are more than 4 months from transplant (6 months at infusion)
  9. For those patients who require leukapheresis for T cell collection (i.e. no previously collected product exists), adequate venous access for apheresis or eligible for appropriate catheter placement, and no other contraindications for leukapheresis.
  10. Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy.

10. Voluntary informed consent is given.

Exclusion Criteria:

  1. Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion.
  2. Uncontrolled active infection.
  3. Active hepatitis B or hepatitis C infection.
  4. Concurrent use of systemic steroids at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of inhaled steroids, or hydrocortisone for physiological replacement in patients with adrenal insufficiency are permitted as well.
  5. Presence of grade 2-4 acute or extensive chronic GVHD.
  6. Under treatment for GVHD.
  7. Previous treatment with any gene therapy products.
  8. Feasibility assessment during screening shows insufficient expansion in response to CD3/CD28 costimulation.
  9. Any uncontrolled active medical disorder that would preclude participation as outlined.
  10. HIV infection.
  11. Patients with active CNS involvement with malignancy (i.e. CNS3 for ALL). Patients with prior CNS disease that has been effectively treated will be eligible. Routine CNS prophylaxis for ALL is permitted.
  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: NCT01626495

Contacts
Contact: Stephan A Grupp, MD, PhD 267-426-0762 grupp@email.chop.edu

Locations
United States, Pennsylvania
CHOP - http://www.chop.edu/service/oncology/pediatric-cancer-research/cart-19-trial.html Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Christine Strait, BS       straitc@email.chop.edu   
Contact: Mia Bension Smith       oncointake@email.chop.edu   
Principal Investigator: Stephan A Grupp, MD, PHD         
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: Stephan A Grupp, MD,PhD Children's Hospital of Philadelphia
  More Information

No publications provided by University of Pennsylvania

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01626495     History of Changes
Other Study ID Numbers: 10-007706  CHP-959 
Study First Received: June 18, 2012
Last Updated: January 19, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Pennsylvania:
Biological: CART19

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

ClinicalTrials.gov processed this record on February 08, 2016