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

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: NCT01626495
Recruitment Status : Completed
First Posted : June 22, 2012
Results First Posted : March 23, 2020
Last Update Posted : March 23, 2020
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions B Cell Leukemia
B Cell Lymphoma
Intervention Biological: CART-19
Enrollment 73
Recruitment Details  
Pre-assignment Details  
Arm/Group Title CART-19 T Cells
Hide Arm/Group Description

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.

CART-19: Day 0: 10% of total dose Day 1: 30% of total dose if patient is stable (no significant toxicity) from prior dose.

Period Title: Overall Study
Started 73 [1]
Intervention 62
Completed 21 [2]
Not Completed 52
Reason Not Completed
Adverse Event             3
Disease progression             27
Withdrawal by Subject             1
Administrative problem             1
Death             2
Physician Decision             1
New cancer therapy             16
Manufacturing failure             1
[1]
Number of enrolled subjects
[2]
Follow up phase completed as per protocol
Arm/Group Title CART-19 T Cells
Hide Arm/Group Description

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.

CART-19: Day 0: 10% of total dose Day 1: 30% of total dose if patient is stable (no significant toxicity) from prior dose.

Overall Number of Baseline Participants 62
Hide Baseline Analysis Population Description
Subjects that received study treatment
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 62 participants
<=18 years
54
  87.1%
Between 18 and 65 years
8
  12.9%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 62 participants
12  (5.25)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 62 participants
Female
28
  45.2%
Male
34
  54.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 62 participants
American Indian or Alaska Native
0
   0.0%
Asian
2
   3.2%
Native Hawaiian or Other Pacific Islander
1
   1.6%
Black or African American
4
   6.5%
White
53
  85.5%
More than one race
0
   0.0%
Unknown or Not Reported
2
   3.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 62 participants
62
1.Primary Outcome
Title Number of Subjects With Study Related Adverse Events.
Hide Description Inclusive of any events that are "possibly", "likely", or "definitely" related to study treatment any time from the first day of study treatment until week 24.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title CART-19 T Cells
Hide Arm/Group Description:

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.

CART-19: Day 0: 10% of total dose Day 1: 30% of total dose if patient is stable (no significant toxicity) from prior dose.

Overall Number of Participants Analyzed 62
Measure Type: Count of Participants
Unit of Measure: Participants
59
  95.2%
2.Secondary Outcome
Title The Number of Subjects With a Successful Product Manufactured
Hide Description [Not Specified]
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title CART-19 T Cells
Hide Arm/Group Description:

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.

CART-19: Day 0: 10% of total dose Day 1: 30% of total dose if patient is stable (no significant toxicity) from prior dose.

Overall Number of Participants Analyzed 62
Measure Type: Count of Participants
Unit of Measure: Participants
60
  96.8%
3.Secondary Outcome
Title Number of Subjects With Complete Remission (CR).
Hide Description

Complete remission rate for subjects with Non-CNS3 ALL.

National Comprehensive Cancer Network standard response criteria, which define complete remission (CR) as ,5% bone marrow blasts by morphologic determination, with no evidence of extramedullary disease or refractory disease.

Time Frame 4 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title CART-19 T Cells
Hide Arm/Group Description:

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.

CART-19: Day 0: 10% of total dose Day 1: 30% of total dose if patient is stable (no significant toxicity) from prior dose.

Overall Number of Participants Analyzed 62
Measure Type: Count of Participants
Unit of Measure: Participants
16
  25.8%
4.Secondary Outcome
Title Number of Subjects With Complete Remission With Incomplete Blood Count Recovery (CRi).
Hide Description

Complete remission rate for subjects with Non-CNS3 ALL.

National Comprehensive Cancer Network standard response criteria, which define complete remission (CR) as ,5% bone marrow blasts by morphologic determination, with no evidence of extramedullary disease or refractory disease.

Time Frame 4 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title CART-19 T Cells
Hide Arm/Group Description:

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.

CART-19: Day 0: 10% of total dose Day 1: 30% of total dose if patient is stable (no significant toxicity) from prior dose.

Overall Number of Participants Analyzed 62
Measure Type: Count of Participants
Unit of Measure: Participants
38
  61.3%
Time Frame 2 Years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title CART-19 T Cells
Hide Arm/Group Description

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.

CART-19: Day 0: 10% of total dose Day 1: 30% of total dose if patient is stable (no significant toxicity) from prior dose.

All-Cause Mortality
CART-19 T Cells
Affected / at Risk (%)
Total   2/73 (2.74%) 
Hide Serious Adverse Events
CART-19 T Cells
Affected / at Risk (%)
Total   58/73 (79.45%) 
Blood and lymphatic system disorders   
Febrile neutropenia * 1  46/73 (63.01%) 
Disseminated intravascular coagulation * 1  6/73 (8.22%) 
Coagulopathy * 1  3/73 (4.11%) 
Hypofibrinogenaemia * 1  1/73 (1.37%) 
Haemolysis * 1  1/73 (1.37%) 
Cardiac disorders   
Left ventricular dysfunction * 1  4/73 (5.48%) 
Bradycardia * 1  1/73 (1.37%) 
Cardio-respiratory arrest * 1  1/73 (1.37%) 
Atrial thrombosis * 1  1/73 (1.37%) 
Endocrine disorders   
Adrenal insufficiency * 1  1/73 (1.37%) 
Eye disorders   
Visual impairment * 1  1/73 (1.37%) 
Gastrointestinal disorders   
Abdominal pain * 1  1/73 (1.37%) 
Haematochezia * 1  1/73 (1.37%) 
Vomiting * 1  2/73 (2.74%) 
Nausea * 1  1/73 (1.37%) 
General disorders   
Pyrexia * 1  15/73 (20.55%) 
Vascular stent thrombosis * 1  1/73 (1.37%) 
Facial pain * 1  1/73 (1.37%) 
Pain * 1  3/73 (4.11%) 
Complication associated with device * 1  1/73 (1.37%) 
Immune system disorders   
Cytokine release syndrome * 1  52/73 (71.23%) 
Anaphylactic reaction * 1  1/73 (1.37%) 
Infections and infestations   
Device related infection * 1  5/73 (6.85%) 
Lung infection * 1  1/73 (1.37%) 
Staphylococcal infection * 1  1/73 (1.37%) 
Streptococcal infection * 1  1/73 (1.37%) 
Varicella zoster virus infection * 1  1/73 (1.37%) 
Bk virus infection * 1  1/73 (1.37%) 
Enterococcal bacteraemia * 1  1/73 (1.37%) 
Gastroenteritis salmonella * 1  1/73 (1.37%) 
Klebsiella infection * 1  1/73 (1.37%) 
Stomatococcal infection * 1  1/73 (1.37%) 
Pyomyositis * 1  1/73 (1.37%) 
Staphylococcal skin infection * 1  1/73 (1.37%) 
Staphylococcal bacteraemia * 1  1/73 (1.37%) 
Clostridium difficile colitis * 1  1/73 (1.37%) 
Injury, poisoning and procedural complications   
Thermal burn * 1  1/73 (1.37%) 
Transfusion reaction * 1  1/73 (1.37%) 
Lower limb fracture * 1  1/73 (1.37%) 
Investigations   
Weight decreased * 1  1/73 (1.37%) 
Metabolism and nutrition disorders   
Dehydration * 1  5/73 (6.85%) 
Decreased appetite * 1  1/73 (1.37%) 
Hyperkalaemia * 1  1/73 (1.37%) 
Hypokalaemia * 1  1/73 (1.37%) 
Tumour lysis syndrome * 1  1/73 (1.37%) 
Acidosis * 1  1/73 (1.37%) 
Musculoskeletal and connective tissue disorders   
Pain in extremity * 1  1/73 (1.37%) 
Bone pain * 1  1/73 (1.37%) 
Arthralgia * 1  1/73 (1.37%) 
Nervous system disorders   
Encephalopathy * 1  17/73 (23.29%) 
Seizure * 1  4/73 (5.48%) 
Generalised tonic-clonic seizure * 1  1/73 (1.37%) 
Headache * 1  3/73 (4.11%) 
Speech disorder * 1  1/73 (1.37%) 
Unresponsive to stimuli * 1  1/73 (1.37%) 
Central nervous system haemorrhage * 1  1/73 (1.37%) 
Facial paresis * 1  1/73 (1.37%) 
Psychiatric disorders   
Mental status changes * 1  1/73 (1.37%) 
Confusional state * 1  1/73 (1.37%) 
Renal and urinary disorders   
Acute kidney injury * 1  5/73 (6.85%) 
Respiratory, thoracic and mediastinal disorders   
Hypoxia * 1  10/73 (13.70%) 
Acute respiratory distress syndrome * 1  4/73 (5.48%) 
Apnoea * 1  1/73 (1.37%) 
Epistaxis * 1  1/73 (1.37%) 
Pleural effusion * 1  1/73 (1.37%) 
Respiratory alkalosis * 1  1/73 (1.37%) 
Respiratory distress * 1  1/73 (1.37%) 
Respiratory failure * 1  1/73 (1.37%) 
Acute respiratory failure * 1  1/73 (1.37%) 
Asthma * 1  1/73 (1.37%) 
Aspiration * 1  1/73 (1.37%) 
Vascular disorders   
Hypotension * 1  24/73 (32.88%) 
Capillary leak syndrome * 1  10/73 (13.70%) 
Hypertension * 1  1/73 (1.37%) 
1
Term from vocabulary, CTCAE (3.0)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 4%
CART-19 T Cells
Affected / at Risk (%)
Total   62/73 (84.93%) 
Blood and lymphatic system disorders   
Febrile neutropenia * 1  10/73 (13.70%) 
Lymphopenia * 1  50/73 (68.49%) 
Splenomegaly * 1  5/73 (6.85%) 
Anaemia * 1  3/73 (4.11%) 
Cardiac disorders   
Sinus tachycardia * 1  12/73 (16.44%) 
Tachycardia * 1  30/73 (41.10%) 
Eye disorders   
Conjunctival haemorrhage * 1  4/73 (5.48%) 
Diplopia * 1  4/73 (5.48%) 
Photophobia * 1  4/73 (5.48%) 
Vision blurred * 1  3/73 (4.11%) 
Gastrointestinal disorders   
Abdominal pain * 1  21/73 (28.77%) 
Constipation * 1  10/73 (13.70%) 
Diarrhoea * 1  35/73 (47.95%) 
Haematochezia * 1  4/73 (5.48%) 
Nausea * 1  45/73 (61.64%) 
Vomiting * 1  48/73 (65.75%) 
Gingival bleeding * 1  3/73 (4.11%) 
Mouth haemorrhage * 1  3/73 (4.11%) 
General disorders   
Chills * 1  27/73 (36.99%) 
Fatigue * 1  29/73 (39.73%) 
Pain * 1  28/73 (38.36%) 
Pyrexia * 1  15/73 (20.55%) 
Catheter site haemorrhage * 1  3/73 (4.11%) 
Catheter site pain * 1  3/73 (4.11%) 
Complication associated with device * 1  3/73 (4.11%) 
Face oedema * 1  3/73 (4.11%) 
Generalised oedema * 1  3/73 (4.11%) 
Withdrawal syndrome * 1  3/73 (4.11%) 
Hepatobiliary disorders   
Hepatomegaly * 1  5/73 (6.85%) 
Hyperbilirubinaemia * 1  13/73 (17.81%) 
Immune system disorders   
Cytokine release syndrome * 1  5/73 (6.85%) 
Hypogammaglobulinaemia * 1  42/73 (57.53%) 
Seasonal allergy * 1  3/73 (4.11%) 
Infections and infestations   
Otitis media * 1  6/73 (8.22%) 
Pneumonia * 1  4/73 (5.48%) 
Respiratory syncytial virus infection * 1  4/73 (5.48%) 
Sinusitis * 1  10/73 (13.70%) 
Upper respiratory tract infection * 1  11/73 (15.07%) 
Urinary tract infection * 1  4/73 (5.48%) 
Clostridium difficile colitis * 1  3/73 (4.11%) 
Escherichia urinary tract infection * 1  3/73 (4.11%) 
Oral candidiasis * 1  3/73 (4.11%) 
Rhinitis * 1  3/73 (4.11%) 
Injury, poisoning and procedural complications   
Contusion * 1  7/73 (9.59%) 
Fall * 1  4/73 (5.48%) 
Infusion related reaction * 1  4/73 (5.48%) 
Procedural pain * 1  11/73 (15.07%) 
Transfusion reaction * 1  3/73 (4.11%) 
Investigations   
Activated partial thromboplastin time prolonged * 1  22/73 (30.14%) 
Alanine aminotransferase increased * 1  45/73 (61.64%) 
Aspartate aminotransferase increased * 1  46/73 (63.01%) 
Blood bilirubin increased * 1  15/73 (20.55%) 
Blood creatinine increased * 1  23/73 (31.51%) 
Blood fibrinogen decreased * 1  11/73 (15.07%) 
Blood immunoglobulin A decreased * 1  5/73 (6.85%) 
Blood immunoglobulin M decreased * 1  5/73 (6.85%) 
Blood uric acid increased * 1  11/73 (15.07%) 
Haemoglobin decreased * 1  57/73 (78.08%) 
International normalised ratio increased * 1  16/73 (21.92%) 
Lipase increased * 1  4/73 (5.48%) 
Lymphocyte count decreased * 1  6/73 (8.22%) 
Neutrophil count decreased * 1  56/73 (76.71%) 
Platelet count decreased * 1  54/73 (73.97%) 
Weight decreased * 1  5/73 (6.85%) 
White blood cell count decreased * 1  58/73 (79.45%) 
Amylase increased * 1  3/73 (4.11%) 
Prothrombin time prolonged * 1  3/73 (4.11%) 
Metabolism and nutrition disorders   
Decreased appetite * 1  43/73 (58.90%) 
Hyperglycaemia * 1  7/73 (9.59%) 
Hyperphosphataemia * 1  22/73 (30.14%) 
Hyperuricaemia * 1  8/73 (10.96%) 
Hypocalcaemia * 1  10/73 (13.70%) 
Hypokalaemia * 1  11/73 (15.07%) 
Hyponatraemia * 1  6/73 (8.22%) 
Hypophosphataemia * 1  15/73 (20.55%) 
Metabolic acidosis * 1  8/73 (10.96%) 
Dehydration * 1  3/73 (4.11%) 
Hypernatraemia * 1  3/73 (4.11%) 
Hypoglycaemia * 1  3/73 (4.11%) 
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  9/73 (12.33%) 
Back pain * 1  5/73 (6.85%) 
Myalgia * 1  14/73 (19.18%) 
Neck pain * 1  4/73 (5.48%) 
Pain in extremity * 1  14/73 (19.18%) 
Pain in jaw * 1  4/73 (5.48%) 
Joint range of motion decreased * 1  3/73 (4.11%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Skin papilloma * 1  3/73 (4.11%) 
Nervous system disorders   
Dizziness * 1  12/73 (16.44%) 
Headache * 1  46/73 (63.01%) 
Tremor * 1  4/73 (5.48%) 
Product Issues   
Device occlusion * 1  4/73 (5.48%) 
Psychiatric disorders   
Anxiety * 1  5/73 (6.85%) 
Confusional state * 1  15/73 (20.55%) 
Insomnia * 1  8/73 (10.96%) 
Depression * 1  3/73 (4.11%) 
Irritability * 1  3/73 (4.11%) 
Renal and urinary disorders   
Haematuria * 1  4/73 (5.48%) 
Acute kidney injury * 1  3/73 (4.11%) 
Dysuria * 1  3/73 (4.11%) 
Reproductive system and breast disorders   
Rhinorrhoea * 1  16/73 (21.92%) 
Respiratory, thoracic and mediastinal disorders   
Cough * 1  35/73 (47.95%) 
Dyspnoea * 1  4/73 (5.48%) 
Epistaxis * 1  15/73 (20.55%) 
Hypoxia * 1  9/73 (12.33%) 
Nasal congestion * 1  13/73 (17.81%) 
Oropharyngeal pain * 1  6/73 (8.22%) 
Pleural effusion * 1  6/73 (8.22%) 
Tachypnoea * 1  10/73 (13.70%) 
Pulmonary oedema * 1  3/73 (4.11%) 
Rhinitis allergic * 1  3/73 (4.11%) 
Skin and subcutaneous tissue disorders   
Dermatitis * 1  4/73 (5.48%) 
Petechiae * 1  9/73 (12.33%) 
Pruritus generalised * 1  6/73 (8.22%) 
Rash * 1  8/73 (10.96%) 
Rash erythematous * 1  6/73 (8.22%) 
Rash papular * 1  8/73 (10.96%) 
Skin lesion * 1  6/73 (8.22%) 
Dry skin * 1  3/73 (4.11%) 
Eczema * 1  3/73 (4.11%) 
Vascular disorders   
Hypertension * 1  13/73 (17.81%) 
Hypotension * 1  13/73 (17.81%) 
1
Term from vocabulary, CTCAE (3.0)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Regulatory Lead
Organization: University of Pennsylvania
Phone: 215-662-4484
EMail: psom-ind-ide@pobox.upenn.edu
Layout table for additonal information
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01626495    
Other Study ID Numbers: 10-007706, 815870
CHP959 ( Other Identifier: Children's Hospital of Philadelphia )
First Submitted: June 18, 2012
First Posted: June 22, 2012
Results First Submitted: February 14, 2020
Results First Posted: March 23, 2020
Last Update Posted: March 23, 2020