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Pilot Study of Redirected Autologous T Cells Engineered to Contain Humanized Anti-CD19 in Patients With Relapsed or Refractory CD19+ Leukemia and Lymphoma Previously Treated With Cell Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02374333
Recruitment Status : Recruiting
First Posted : February 27, 2015
Last Update Posted : March 22, 2019
Information provided by (Responsible Party):
University of Pennsylvania

Brief Summary:
This is a pilot study to evaluate humanized CD19 redirected autologous T cells (or huCART19 cells) in patients with relapsed or refractory CD19+ leukemia and lymphoma that was previously treated with cell therapy. This study is targeting pediatric patients aged 1-24 years with CD19+ B cell malignancies with no available curative treatment options (such as autologous or allogeneic stem cell transplantation) who have a limited prognosis with currently available therapies and were previously treated with a B cell directed engineered cell therapy product.

Condition or disease Intervention/treatment Phase
Acute Lymphocytic Leukemia Diffuse Large Cell Lymphoma Biological: huCART19 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 85 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Redirected Autologous T Cells Engineered to Contain Humanized Anti-CD19 Attached to TCRζ and 4-1BB Signaling Domains in Patients With Relapsed or Refractory CD19+ Leukemia and Lymphoma Previously Treated With Cell Therapy
Study Start Date : March 2014
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : November 2020

Arm Intervention/treatment
Experimental: huCART19
CART19 cells transduced with a lentiviral vector to express humanized anti-CD19 administered by IV injection
Biological: huCART19
Other Name: huCTL019

Primary Outcome Measures :
  1. Occurrence of study related adverse events defined as NCI CTCAE 4.0 > grade 3 possibly, probably, or definitely related to study treatment. [ Time Frame: Study treatment until Week 24 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 24 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Male and female subjects with documented CD19+ B cell malignancies and 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. In general, these will be patients with:

    1. ALL without curative options for therapy, including those not eligible for allogeneic SCT. 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.
    2. Diffuse large cell lymphoma or other high-grade NHL, previously identified as CD19+ including residual disease after primary therapy and not eligible for autologous SCT; relapsed after prior autologous SCT; beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT.
  2. Patients previously treated with B cell directed engineered cell therapy are eligible if they meet one of the following criteria:

    1. partial response or no response to prior cell therapy
    2. relapsed after prior cell therapy
    3. demonstrated B cell recovery suggesting loss of engineered cells.
  3. Documented CD19 expression (after previous B cell directed cell therapy, if applicable)
  4. Age 1 to 24 years
  5. Expected survival > 12 weeks
  6. Creatinine < 2.5 mg/dl and less than 2.5x normal for age
  7. Bilirubin <2.0 mg/dl
  8. Adequate pulmonary function defined as < Grade 3 hypoxia
  9. Adequate cardiac function defined as LVSF ≥ 28% confirmed by ECHO
  10. Adequate performance status (Lansky or Karnofsky score ≥50)
  11. 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)
  12. Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy
  13. 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.
  14. 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 physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
  5. Presence of grade 2-4 acute or extensive chronic GVHD.
  6. Under treatment for GVHD.
  7. CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity
  8. Any uncontrolled active medical disorder that would preclude participation as outlined.
  9. HIV infection

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 identifier (NCT number): NCT02374333

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Contact: Christine Barker 267-425-5827

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United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Christine Barker    267-425-5837   
Contact: Maya Mudambi    267-425-0193   
Principal Investigator: Shannon Maude, MD, PhD         
Sponsors and Collaborators
University of Pennsylvania
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Study Chair: Carl June, MD University of Pennsylvania

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Responsible Party: University of Pennsylvania Identifier: NCT02374333     History of Changes
Other Study ID Numbers: 13BT022, 819851
First Posted: February 27, 2015    Key Record Dates
Last Update Posted: March 22, 2019
Last Verified: March 2019

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