- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02030847
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
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
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Abramson Cancer Center of the University of Pennsylvania
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria
- Signed informed consent form must be obtained prior to any study procedure
Relapsed or refractory B-cell ALL
- 1st or greater BM relapse OR
- Any marrow relapse after allogeneic HSCT and > 100 days from transplant OR
- 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:
- Creatinine < 1.6 mg/dl
- ALT/AST < 3x upper limit of normal range
- Direct 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 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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.
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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
As of June 2014, dose was reduced to a single dose of 1-5x10^7 CART-19 cells.
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.
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).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Complete Remission Rate at Day 28 After CART-19 Therapy
Time Frame: 28 Days
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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 |
28 Days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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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.
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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
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Noelle Frey, MD, Abramson Cancer Center at Penn Medicine
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- UPCC 21413, 818626
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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