Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02030847
Recruitment Status : Completed
First Posted : January 9, 2014
Results First Posted : May 24, 2019
Last Update Posted : August 30, 2019
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Patients With B Cell ALL, Relapsed or Refractory, With no Available Curative Treatment Options
Intervention Biological: CART-19
Enrollment 42
Recruitment Details Patients were identified through the clinical practices of the investigator or sub-investigators and through referrals from outside hospitals and physicians. No direct-to-patient advertising was performed.
Pre-assignment Details  
Arm/Group Title Arm1
Hide Arm/Group Description

Phase II study to determine the efficacy & 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.

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

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

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.

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

Period Title: Overall Study
Started 42
Completed 5
Not Completed 37
Reason Not Completed
Death             10
Disease Progression             15
New Cancer Therapy             8
Physician Decision             3
Withdrawal by Subject             1
Arm/Group Title Arm1
Hide Arm/Group Description

phase II study to determine the efficacy & 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.

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

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

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.

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

Overall Number of Baseline Participants 30
Hide Baseline Analysis Population Description
Out of 42 enrolled, only 30 patients were infused with CART-19 product. 30 infused patients were considered for baseline analysis.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants
39.6  (16.34)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 30 participants
>=18 to <40 Years 18
>=40 to <65 Years 10
>=65 Years 2
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Female
10
  33.3%
Male
20
  66.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Hispanic or Latino
2
   6.7%
Not Hispanic or Latino
28
  93.3%
Unknown or Not Reported
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 30 participants
Caucasian 28
Asian 1
Other 1
1.Primary Outcome
Title Overall Complete Remission Rate at Day 28 After CART-19 Therapy
Hide Description

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

Time Frame 28 Days
Hide Outcome Measure Data
Hide Analysis Population Description
Out of 42 enrolled, only 30 patients were infused with CART-19 product. 30 infused patients were considered for outcome measure.
Arm/Group Title Arm1
Hide Arm/Group Description:

phase II study to determine the efficacy & 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.

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

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

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.

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

Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Remission (CR)
8
  26.7%
CR with incomplete blood count recovery (CRi)
10
  33.3%
No Response
6
  20.0%
Unknown
6
  20.0%
2.Secondary Outcome
Title Best Overall Response
Hide Description 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.
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
Hide Outcome Measure Data
Hide Analysis Population Description
Out of 42 enrolled, only 30 patients were infused with CART-19 product. 30 infused patients were considered for outcome measure.
Arm/Group Title Arm1
Hide Arm/Group Description:

Phase II study to determine the efficacy & 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.

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

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

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.

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).

Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Remission (CR)
10
  33.3%
CR with incomplete blood count recovery (CRi)
1
   3.3%
No Response
8
  26.7%
Unknown
11
  36.7%
Time Frame 12 Months
Adverse Event Reporting Description The remaining 12 participants that did not receive IP were not included in the AE Reporting, causing only 30 / 42 to be at risk”.
 
Arm/Group Title Arm1
Hide Arm/Group Description

Phase II study to determine the efficacy & safety of a single infusion of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCRζ & 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.

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.

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

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.

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).

All-Cause Mortality
Arm1
Affected / at Risk (%)
Total   30/42 (71.43%) 
Show Serious Adverse Events Hide Serious Adverse Events
Arm1
Affected / at Risk (%)
Total   30/30 (100.00%) 
Blood and lymphatic system disorders   
Febrile neutropenia * 1  1/30 (3.33%) 
Eye disorders   
Vision blurred * 1  1/30 (3.33%) 
Gastrointestinal disorders   
Constipation * 1  1/30 (3.33%) 
Immune system disorders   
Cytokine Release Syndrome * 1  21/30 (70.00%) 
Infections and infestations   
Sepsis * 1  3/30 (10.00%) 
Pneumonia * 1  2/30 (6.67%) 
Clostridium difficile infection * 1  1/30 (3.33%) 
Influenza * 1  1/30 (3.33%) 
Meningitis * 1  1/30 (3.33%) 
Staphylococcal infection * 1  1/30 (3.33%) 
Metabolism and nutrition disorders   
Acidosis * 1  1/30 (3.33%) 
Nervous system disorders   
Haemorrhage intracranial * 1  1/30 (3.33%) 
Headache * 1  1/30 (3.33%) 
Seizure * 1  1/30 (3.33%) 
Psychiatric disorders   
Suicide attempt * 1  1/30 (3.33%) 
Respiratory, thoracic and mediastinal disorders   
Hypoxia * 1  1/30 (3.33%) 
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm1
Affected / at Risk (%)
Total   30/30 (100.00%) 
Blood and lymphatic system disorders   
Anemia * 1  16/30 (53.33%) 
Thrombocytopenia * 1  4/30 (13.33%) 
Febrile Neutropenia * 1  2/30 (6.67%) 
Neutropenia * 1  2/30 (6.67%) 
Disseminated intravascular coagulation * 1  1/30 (3.33%) 
Cardiac disorders   
Pulseless electrical activity * 1  1/30 (3.33%) 
Sinus Tachycarida * 1  1/30 (3.33%) 
Tachycardia * 1  1/30 (3.33%) 
Ear and labyrinth disorders   
Ear Pain * 1  1/30 (3.33%) 
Eye disorders   
Eye haemorrhage * 1  1/30 (3.33%) 
Papilloedema * 1  1/30 (3.33%) 
Vision blurred * 1  1/30 (3.33%) 
Vitreous haemorrhage * 1  1/30 (3.33%) 
Gastrointestinal disorders   
Diarrhoea * 1  4/30 (13.33%) 
Constipation * 1  2/30 (6.67%) 
Nausea * 1  2/30 (6.67%) 
Stomatitis * 1  2/30 (6.67%) 
Vomiting * 1  2/30 (6.67%) 
Gastrointestinal haemorrhage * 1  1/30 (3.33%) 
Pancreatitis * 1  1/30 (3.33%) 
Tomgue ulceration * 1  1/30 (3.33%) 
General disorders   
Fatigue * 1  5/30 (16.67%) 
Oedema peripheral * 1  5/30 (16.67%) 
Chills * 1  4/30 (13.33%) 
Pyrexia * 1  4/30 (13.33%) 
Generalised Oedema * 1  1/30 (3.33%) 
Influenza like illness * 1  1/30 (3.33%) 
Medical device site pain * 1  1/30 (3.33%) 
Immune system disorders   
Cytokine release syndrome * 1  28/30 (93.33%) 
Infections and infestations   
Sepsis * 1  3/30 (10.00%) 
Clostridium difficile colitis * 1  2/30 (6.67%) 
Pneumonia * 1  2/30 (6.67%) 
Bacterial infection * 1  1/30 (3.33%) 
Clostridium difficile infection * 1  1/30 (3.33%) 
Enterocolitis infections * 1  1/30 (3.33%) 
Influenza * 1  1/30 (3.33%) 
Meningitis * 1  1/30 (3.33%) 
Oral candidiasis * 1  1/30 (3.33%) 
Staphylococoal infection * 1  1/30 (3.33%) 
Vira upper respiratory tract infection * 1  1/30 (3.33%) 
Injury, poisoning and procedural complications   
Tendon injury * 1  1/30 (3.33%) 
Thermal burn * 1  1/30 (3.33%) 
Investigations   
Alanine aminotransferase increased * 1  17/30 (56.67%) 
Asprtate aminotransferase increased * 1  17/30 (56.67%) 
Platelet count decreased * 1  13/30 (43.33%) 
Neurphil count decreased * 1  11/30 (36.67%) 
Blood bilirubin increased * 1  10/30 (33.33%) 
White blood cell count decreased * 1  9/30 (30.00%) 
Blood alkaline phosphate increased * 1  8/30 (26.67%) 
Lymmphocyte count decreased * 1  7/30 (23.33%) 
Blood fibrinogen decreased * 1  5/30 (16.67%) 
Activated partial thromboplastin time prolonged * 1  3/30 (10.00%) 
Cd4 lymphocytes decreased * 1  3/30 (10.00%) 
Alanine aminotransferase * 1  1/30 (3.33%) 
Blood creatinine increased * 1  1/30 (3.33%) 
Ejection fraction decreased * 1  1/30 (3.33%) 
Metabolism and nutrition disorders   
Hypocalcaemia * 1  21/30 (70.00%) 
Hypophosphotaemia * 1  17/30 (56.67%) 
Hyponatraemia * 1  16/30 (53.33%) 
Hypokalemia * 1  14/30 (46.67%) 
Hypoalbuminaemia * 1  12/30 (40.00%) 
Hypomagnesaemia * 1  10/30 (33.33%) 
Decreased appetite * 1  4/30 (13.33%) 
Hyperglycaemia * 1  4/30 (13.33%) 
Hypermagnesaemia * 1  3/30 (10.00%) 
Hypernatraemia * 1  3/30 (10.00%) 
Acidosis * 1  2/30 (6.67%) 
Hypertriglyceridaemia * 1  2/30 (6.67%) 
Hypercalcaemia * 1  1/30 (3.33%) 
Hyperkalaemia * 1  1/30 (3.33%) 
Hypoglycaemia * 1  1/30 (3.33%) 
Tumor lysis syndrom * 1  1/30 (3.33%) 
Musculoskeletal and connective tissue disorders   
Muscular wekness * 1  3/30 (10.00%) 
Myalgia * 1  2/30 (6.67%) 
Arthralgia * 1  1/30 (3.33%) 
Back pain * 1  1/30 (3.33%) 
Bone pain * 1  1/30 (3.33%) 
Muscle haemorrhage * 1  1/30 (3.33%) 
Musculoskeletal pain * 1  1/30 (3.33%) 
Pain in extremity * 1  1/30 (3.33%) 
Pain in Jaw * 1  1/30 (3.33%) 
Nervous system disorders   
Headache * 1  4/30 (13.33%) 
Seizure * 1  3/30 (10.00%) 
Dizziness * 1  1/30 (3.33%) 
Dysgeusia * 1  1/30 (3.33%) 
Encephalopathy * 1  1/30 (3.33%) 
Intracranial Haemorrhage * 1  1/30 (3.33%) 
Neuroptahy peripheral * 1  1/30 (3.33%) 
Psychiatric disorders   
Mental status changes * 1  4/30 (13.33%) 
Insomnia * 1  3/30 (10.00%) 
Confusional state * 1  2/30 (6.67%) 
Agitation * 1  1/30 (3.33%) 
Delirium * 1  1/30 (3.33%) 
Hellucination * 1  1/30 (3.33%) 
Renal and urinary disorders   
Acute kidney injury * 1  5/30 (16.67%) 
Urinary incontinence * 1  1/30 (3.33%) 
Respiratory, thoracic and mediastinal disorders   
Hypoxia * 1  4/30 (13.33%) 
Cough * 1  2/30 (6.67%) 
Dsypnoea * 1  2/30 (6.67%) 
Oropharyngeal pain * 1  2/30 (6.67%) 
Acute respiratory distress syndrome * 1  1/30 (3.33%) 
Dyspnoea exertional * 1  1/30 (3.33%) 
Laryngeal haemorrhage * 1  1/30 (3.33%) 
Laryngeal oedema * 1  1/30 (3.33%) 
Pleural effusion * 1  1/30 (3.33%) 
Productive cough * 1  1/30 (3.33%) 
Pulmonary oedema * 1  1/30 (3.33%) 
Skin and subcutaneous tissue disorders   
Rash * 1  2/30 (6.67%) 
Ecchymosis * 1  1/30 (3.33%) 
Hyperhidrosis * 1  1/30 (3.33%) 
Night sweats * 1  1/30 (3.33%) 
Rash erythematous * 1  1/30 (3.33%) 
Rash maculo-papular * 1  1/30 (3.33%) 
Vascular disorders   
Hypertension * 1  2/30 (6.67%) 
Embolism venous * 1  1/30 (3.33%) 
Hypotension * 1  1/30 (3.33%) 
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Noelle Frey, MD
Organization: Abramson Cancer Center of the University of Pennsylvania
Phone: 215-662-6901
EMail: noelle.frey@uphs.upenn.edu
Layout table for additonal information
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02030847     History of Changes
Other Study ID Numbers: UPCC 21413, 818626
First Submitted: January 7, 2014
First Posted: January 9, 2014
Results First Submitted: April 5, 2019
Results First Posted: May 24, 2019
Last Update Posted: August 30, 2019