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Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCR and 4-1BB Signaling Domains in Patients With Chemotherapy Resistant or Refractory Acute Lymphoblastic Leukemia

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ClinicalTrials.gov Identifier: NCT02030847
Recruitment Status : Completed
First Posted : January 9, 2014
Results First Posted : May 24, 2019
Last Update Posted : May 24, 2019
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

Brief Summary:
This is a single center, single arm, open-label phase II study to determine the efficacy and safety of a single infusion of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR and 4-1BB (TCR/4-1BB) co-stimulatory domains (referred to as CART-19 cells) in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Inclusion criteria are designed to include adult patients aged greater than 18 with B cell ALL, relapsed or refractory, with no available curative treatment options (such as autologous or allogeneic stem cell transplantation) who have limited prognosis (greater than 12 weeks survival expectancy) with currently available therapies. The study product is CART-19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCR:41BB administered by a single i.v. infusion of 1 to 5 x 108 transduced CAR T cells.

Condition or disease Intervention/treatment Phase
Patients With B Cell ALL, Relapsed or Refractory, With no Available Curative Treatment Options Biological: CART-19 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCR and 4-1BB Signaling Domains in Patients With Chemotherapy Resistant or RefractoryAcute Lymphoblastic Leukemia
Actual Study Start Date : February 27, 2014
Actual Primary Completion Date : April 26, 2018
Actual Study Completion Date : April 26, 2018


Arm Intervention/treatment
Experimental: Arm1
phase II study to determine the efficacy and safety of a single infusion of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ/4-1BB) co-stimulatory domains (referred to as "CART-19" cells) in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia.
Biological: CART-19
CART-19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCR:41BB administered by a single i.v. infusion of 1 to 5 x 10^8 transduced CAR T cells

Biological: CART-19
As of June 2014, dose was reduced to a single dose of 1-5x10^7 CART-19 cells.

Biological: CART-19
In the protocol amendment in November 2014, the dose remained 1-5 x 10^7 CART-19 cells, but was revised to be administered via split dosing: 10% on Day 1, 30% on Day 2, 60% on Day 3.

Biological: CART-19
In the protocol amendment in May 2015, the dose was changed to 1-5 x 10^8 CART-19 cells administered via split dosing: 10% on Day 1 (1-5x10^7), 30% on Day 2 (3x10^7-1.5x10^8), 60% on Day 3 (6x10^7-3x10^8).




Primary Outcome Measures :
  1. Overall Complete Remission Rate at Day 28 After CART-19 Therapy [ Time Frame: 28 Days ]

    Overall Complete Remission Rate (ORR) which includes complete remission (CR) and CR with incomplete blood count recovery (CRi) at Day 28.

    Overall Complete Remission Rate = CR+ CRi



Secondary Outcome Measures :
  1. Best Overall Response [ Time Frame: from the start of the treatment until death, last follow up, relapse or start of new anticancer therapy, whichever comes first, assessed up to 12 months ]
    For the secondary efficacy objectives for this study, the number of patients were computed with a best overall disease response of CR or CRi, where the best overall disease response is defined as the best disease response recorded from the start of the treatment until death, last follow up, relapse or start of new anticancer therapy, whichever comes first.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Signed informed consent form must be obtained prior to any study procedure
  • Relapsed or refractory B-cell ALL

    1. 1st or greater BM relapse OR
    2. Any marrow relapse after allogeneic HSCT and > 100 days from transplant OR
    3. For patients with refractory disease:

    i. < 60 years old that have not achieved a CR after > 2 or more chemotherapy regimens ii. >60 years old that have not achieved a CR after 1 prior chemotherapy regimen d. Patients with Ph+ ALL are eligible if they have failed tyrosine kinase inhibitor therapy

  • Documentation of CD19 tumor expression in bone marrow or peripheral blood by flow cytometry within 3 months of screening.
  • Adequate organ function defined as:

    1. Creatinine < 1.6 mg/dl
    2. ALT/AST < 3x upper limit of normal range
    3. Direct bilirubin <2.0 mg/dl
    4. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea, pulse oxygen > 92% on room air, and DLCO > 40% (corrected for anemia if clinically appropriate)
    5. Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
  • Bone marrow with ≥ 5% lymphoblasts
  • Male or female age ≥ 18 years
  • A ECOG Performance Status that is either 0 or 1
  • No contraindications for leukapheresis.

Retreatment Inclusion Criteria

  • Performance Status 0-1
  • Adequate organ system function including:

    • Creatinine < 1.6 mg/dl
    • ALT/AST < 3x upper limit of normal
    • Total Bilirubin < 2.0 mg/dl
    • Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea, pulse oxygen > 92% on room air, and DLCO > 40% (corrected for anemia if clinically appropriate)
  • Left Ventricular Ejection Fraction ≥ 40%
  • No contraindications for leukapheresis (if required for retreatment)
  • Gives voluntary informed consent for retreatment

Exclusion Criteria

  • Isolated extramedullary disease relapse
  • Active hepatitis B or active hepatitis C
  • Class III/IV cardiovascular disability according to the New York Heart Association Classification
  • HIV infection
  • Active acute or chronic graft-versus-host disease (GVHD) or requirement of immunosuppressant medications for GVHD within 4 weeks of enrollment.
  • Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. For additional details regarding use of steroid and immunosuppressant medications.
  • Active CNS involvement by malignancy. Note: Patients with history of CNS disease that has been effectively treated will be eligible provided that treatment was >4 weeks before enrollment
  • Pregnant or nursing (lactating) women, female study participants of reproductive potential must have a negative serum or urine pregnancy test within 48 hours before infusion
  • Participation in a prior investigational study within 4 weeks prior to enrollment or longer if required by local regulation. Participation in non-therapeutic research studies is allowed.
  • Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system.

Retreatment Exclusion Criteria

  • Pregnant or lactating women.
  • Active hepatitis B or hepatitis C
  • Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. For additional details regarding use of steroid or immunosuppressant medications.
  • HIV infection
  • Patients with active CNS involvement with malignancy. Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was >4 weeks before enrollment on the retreatment cohort.
  • Class III/IV cardiovascular disability according to the New York Heart Association Classification
  • Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system.

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): NCT02030847


Locations
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United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Investigators
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Principal Investigator: Noelle Frey, MD Abramson Cancer Center of the University of Pennsylvania
  Study Documents (Full-Text)

Documents provided by University of Pennsylvania:

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Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02030847     History of Changes
Other Study ID Numbers: UPCC 21413, 818626
First Posted: January 9, 2014    Key Record Dates
Results First Posted: May 24, 2019
Last Update Posted: May 24, 2019
Last Verified: May 2019

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