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CART19 to Treat B-Cell Leukemia or Lymphoma That Are Resistant or Refractory to Chemotherapy

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ClinicalTrials.gov Identifier: NCT01029366
Recruitment Status : Completed
First Posted : December 10, 2009
Results First Posted : February 28, 2017
Last Update Posted : June 26, 2019
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Hematopoietic/Lymphoid Cancer
Adult Acute Lymphoblastic Leukemia in Remission
B-cell Adult Acute Lymphoblastic Leukemia
B-cell Chronic Lymphocytic Leukemia
Prolymphocytic Leukemia
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Refractory Chronic Lymphocytic Leukemia
Stage III Adult Diffuse Large Cell Lymphoma
Stage III Chronic Lymphocytic Leukemia
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Grade 3 Follicular Lymphoma
Stage III Mantle Cell Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Chronic Lymphocytic Leukemia
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Intervention Biological: CART-19
Enrollment 26
Recruitment Details Study Start/End Dates 17-Mar-2010 to 06-Jul-2015
Pre-assignment Details  
Arm/Group Title Chronic Lymphocytic Leukemia (CLL) Subjects Acute Lymphocytic Leukemia (ALL) Subjects
Hide Arm/Group Description Patients receive CART-19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRζ:41BB administered on days 0, 1, 2 and 11 in the absence of disease progression or unacceptable toxicity laboratory biomarker analysis polymerase chain reaction reverse transcriptase-polymerase chain reaction anti-CD19-CAR retroviral vector-transduced autologous T cells: Given IV genetically engineered lymphocyte therapy. Subjects were given minimum/maximum total dose: 1.5x10⁷/ 5x10⁹. Patients receive CART-19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRζ:41BB administered on days 0, 1, 2 and 11 in the absence of disease progression or unacceptable toxicity laboratory biomarker analysis polymerase chain reaction reverse transcriptase-polymerase chain reaction anti-CD19-CAR retroviral vector-transduced autologous T cells: Given IV genetically engineered lymphocyte therapy. Subjects were given minimum/maximum total dose: 1.5x10⁷/ 5x10⁹
Period Title: Overall Study
Started 18 8
Completed 14 6
Not Completed 4 2
Reason Not Completed
Withdrawal by Subject             1             0
Death             1             1
disease progression             2             0
manufacturing failure             0             1
Arm/Group Title CLL Subjects ALL Subjects Total
Hide Arm/Group Description Patients receive CART-19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRζ:41BB administered on days 0, 1, 2 and 11 in the absence of disease progression or unacceptable toxicity laboratory biomarker analysis polymerase chain reaction reverse transcriptase-polymerase chain reaction anti-CD19-CAR retroviral vector-transduced autologous T cells: Given IV genetically engineered lymphocyte therapy Patients receive CART-19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRζ:41BB administered on days 0, 1, 2 and 11 in the absence of disease progression or unacceptable toxicity laboratory biomarker analysis polymerase chain reaction reverse transcriptase-polymerase chain reaction anti-CD19-CAR retroviral vector-transduced autologous T cells: Given IV genetically engineered lymphocyte therapy Total of all reporting groups
Overall Number of Baseline Participants 14 6 20
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 6 participants 20 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
7
  50.0%
5
  83.3%
12
  60.0%
>=65 years
7
  50.0%
1
  16.7%
8
  40.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 6 participants 20 participants
Female
2
  14.3%
1
  16.7%
3
  15.0%
Male
12
  85.7%
5
  83.3%
17
  85.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 6 participants 20 participants
Hispanic or Latino
0
   0.0%
2
  33.3%
2
  10.0%
Not Hispanic or Latino
14
 100.0%
4
  66.7%
18
  90.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 6 participants 20 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
1
  16.7%
1
   5.0%
White
14
 100.0%
5
  83.3%
19
  95.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Number of Participants With Adverse Events
Hide Description [Not Specified]
Time Frame 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Participants
Hide Arm/Group Description:

Patients receive CART-19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRζ:41BB administered on days 0, 1, 2 and 11 in the absence of disease progression or unacceptable toxicity laboratory biomarker analysis

polymerase chain reaction

reverse transcriptase-polymerase chain reaction

anti-CD19-CAR retroviral vector-transduced autologous T cells: Given IV

genetically engineered lymphocyte therapy

Overall Number of Participants Analyzed 20
Measure Type: Number
Unit of Measure: participants
20
2.Secondary Outcome
Title Overall Response Summary
Hide Description

Efficacy assessments for ALL were performed based on bone marrow and blood morphologic criteria and physical examination findings. The definitions for response are primarily based on the standardized response criteria defined by National Comprehensive Cancer Network (NCCN) Guidelines (NCCN, 2013 v.1).

Efficacy assessments for CLL were based on lymphadenopathy, hepatomegaly, splenomegaly, bone marrow and blood morphologic and laboratory assessments. The response criteria are consistent with NCCN Guidelines Version 2.2012 CLL/SLL, which is based on the 2008 International Workshop Group on CLL (IWCLL) revisions of the original guidelines for evaluating disease response released in 1996 by the National Cancer Institute Working Group (NCI/WG).

Time Frame 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title CLL Subjects ALL Subjects
Hide Arm/Group Description:

Patients receive CART-19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRζ:41BB administered on days 0, 1, 2 and 11 in the absence of disease progression or unacceptable toxicity

laboratory biomarker analysis

polymerase chain reaction

reverse transcriptase-polymerase chain reaction

anti-CD19-CAR retroviral vector-transduced autologous T cells: Given IV

genetically engineered lymphocyte therapy

Patients receive CART-19 cells transduced with a lentiviral vector to express anti-CD19 scFv TCRζ:41BB administered on days 0, 1, 2 and 11 in the absence of disease progression or unacceptable toxicity

laboratory biomarker analysis

polymerase chain reaction

reverse transcriptase-polymerase chain reaction

anti-CD19-CAR retroviral vector-transduced autologous T cells: Given IV

genetically engineered lymphocyte therapy

Overall Number of Participants Analyzed 14 6
Measure Type: Number
Unit of Measure: percentage of participants
Complete Remission 21.4 83.4
Partial Remission 21.4 0
No Remission 57.1 16.7
Overall Response Rate 42.9 83.3
Time Frame 2 years
Adverse Event Reporting Description Adverse events during post-infusion period, regardless of study drug relationship, by primary system organ class and maximum CTC grade
 
Arm/Group Title Chronic Lymphocytic Leukemia Acute Lymphocytic Leukemia
Hide Arm/Group Description CART-19 (autologous T cells transduced with CD19 TCR-ζ/4-1BB vector) administered as an IV infusion. Minimum/maximum total dose: 1.5x10^7 / 5x10^9. CART-19 (autologous T cells transduced with CD19 TCR-ζ/4-1BB vector) administered as an IV infusion. Minimum/maximum total dose: 1.5x10^7 / 5x10^9.
All-Cause Mortality
Chronic Lymphocytic Leukemia Acute Lymphocytic Leukemia
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Chronic Lymphocytic Leukemia Acute Lymphocytic Leukemia
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/14 (100.00%)      6/6 (100.00%)    
Blood and lymphatic system disorders     
Febrile Neutropenia  2  3/14 (21.43%)  3 0/6 (0.00%)  0
anaemia  1  2/14 (14.29%)  2 0/6 (0.00%)  0
Haemolytic anaemia  1  1/14 (7.14%)  1 0/6 (0.00%)  0
Cardiac disorders     
Myocardial Infarction  1  1/14 (7.14%)  1 0/6 (0.00%)  0
General disorders     
pyrexia  2  4/14 (28.57%)  4 1/6 (16.67%)  1
Chest Discomfort  1  1/14 (7.14%)  1 0/6 (0.00%)  0
Chills  1  1/14 (7.14%)  1 0/6 (0.00%)  0
Pain in extremity  1  1/14 (7.14%)  1 0/6 (0.00%)  0
Immune system disorders     
Cytokine Release Syndrome  1 [1]  6/14 (42.86%)  6 5/6 (83.33%)  5
Infections and infestations     
Pneumonia  1  2/14 (14.29%)  2 0/6 (0.00%)  0
Cellulitis  1  1/14 (7.14%)  1 0/6 (0.00%)  0
Clostridium difficle infection  1  1/14 (7.14%)  1 0/6 (0.00%)  0
Influenza like illness  1  1/14 (7.14%)  1 0/6 (0.00%)  0
Neutropenic sepsis  1  1/14 (7.14%)  1 0/6 (0.00%)  0
Pneumonia fungal  1  1/14 (7.14%)  1 0/6 (0.00%)  0
Pseudomas Infection  1  1/14 (7.14%)  1 0/6 (0.00%)  0
Investigations     
Histocytosis Haematophagic  1  1/14 (7.14%)  1 0/6 (0.00%)  0
Metabolism and nutrition disorders     
Tumor Lysis Syndrome  1  2/14 (14.29%)  2 0/6 (0.00%)  0
Nervous system disorders     
Headache  1  1/14 (7.14%)  1 0/6 (0.00%)  0
Psychiatric disorders     
Confusion State  1  1/14 (7.14%)  1 0/6 (0.00%)  0
Renal and urinary disorders     
Acute Kidney Injury  1  1/14 (7.14%)  1 0/6 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  1  2/14 (14.29%)  2 0/6 (0.00%)  0
Dyspnoea  1  1/14 (7.14%)  1 0/6 (0.00%)  0
Vascular disorders     
Hypertension  1  1/14 (7.14%)  1 0/6 (0.00%)  0
Hypotension  1  1/14 (7.14%)  1 0/6 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAEv3.0
2
Term from vocabulary, CTCAE
[1]
Grading of this event was performed using a modified grading scale based upon CRS in the context of the experimental agent.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Chronic Lymphocytic Leukemia Acute Lymphocytic Leukemia
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/14 (100.00%)      6/6 (100.00%)    
Blood and lymphatic system disorders     
Neutropenia  2  7/14 (50.00%)  7 3/6 (50.00%)  3
Anaemia  2  6/14 (42.86%)  6 4/6 (66.67%)  4
Thrombocytopenia  2  6/14 (42.86%)  6 2/6 (33.33%)  2
Lymphopenia  2  5/14 (35.71%)  5 0/6 (0.00%)  0
Neutrophil count decreased  2  5/14 (35.71%)  5 0/6 (0.00%)  0
Febrile Neutropenia  2  4/14 (28.57%)  4 2/6 (33.33%)  2
Lymphocyte count decreased  2  4/14 (28.57%)  4 0/6 (0.00%)  0
Cardiac disorders     
Tachycardia  2  5/14 (35.71%)  5 2/6 (33.33%)  2
ATrial fibrillation  2  3/14 (21.43%)  3 0/6 (0.00%)  0
Gastrointestinal disorders     
Nausea  2  8/14 (57.14%)  8 1/6 (16.67%)  1
Diarrhoea  2  7/14 (50.00%)  7 4/6 (66.67%)  4
Gastrooesophageal reflux disease  2  4/14 (28.57%)  4 2/6 (33.33%)  2
Abdominal distension  2  3/14 (21.43%)  3 0/6 (0.00%)  0
Constipation  2  3/14 (21.43%)  3 1/6 (16.67%)  1
General disorders     
Fatigue  1  13/14 (92.86%)  13 2/6 (33.33%)  2
Pyrexia  2  11/14 (78.57%)  11 2/6 (33.33%)  2
Chills  1  8/14 (57.14%)  8 0/6 (0.00%)  0
Odema Peripheral  2  7/14 (50.00%)  7 2/6 (33.33%)  2
Immune system disorders     
Cytokine Release Syndrome  2  8/14 (57.14%)  8 6/6 (100.00%)  6
Investigations     
Blood Albumin decreased  2  8/14 (57.14%)  8 1/6 (16.67%)  1
White Blood Cell Count Decreased  2  8/14 (57.14%)  8 2/6 (33.33%)  2
Blood Calcium decreased  2  6/14 (42.86%)  6 1/6 (16.67%)  1
Blood Sosoim decreased  2  6/14 (42.86%)  6 1/6 (16.67%)  1
Aspartate aminotransferase increased  2  5/14 (35.71%)  5 0/6 (0.00%)  0
Blood Glucose increased  2  5/14 (35.71%)  5 0/6 (0.00%)  0
Alanine aminotransferase increased  2  4/14 (28.57%)  4 1/6 (16.67%)  1
Blood Glucose decreased  2  4/14 (28.57%)  4 0/6 (0.00%)  0
Blood Magnesium decreased  2  4/14 (28.57%)  4 1/6 (16.67%)  1
Hypomagnesaemia  2  4/14 (28.57%)  4 0/6 (0.00%)  0
Blood Alkaline phosphatase increased  2  3/14 (21.43%)  3 0/6 (0.00%)  0
Blood bilirubin increased  1  3/14 (21.43%)  3 0/6 (0.00%)  0
blood creatinine increased  2  3/14 (21.43%)  3 0/6 (0.00%)  0
Blood lactate dehydrogenase increased  2  3/14 (21.43%)  3 0/6 (0.00%)  0
Blood phosphorous decreased  2  3/14 (21.43%)  3 3/6 (50.00%)  3
Blood urinc acid increased  2  3/14 (21.43%)  3 0/6 (0.00%)  0
platelet count decreased  2  3/14 (21.43%)  3 1/6 (16.67%)  1
Metabolism and nutrition disorders     
Hypokalemia  2  7/14 (50.00%)  7 3/6 (50.00%)  3
Decreased Appetite  2  6/14 (42.86%)  6 0/6 (0.00%)  0
Hypocalcaemia  2  3/14 (21.43%)  3 1/6 (16.67%)  1
Tumor Lysis Syndrome  2  3/14 (21.43%)  3 1/6 (16.67%)  1
Hyperglycaemia  2  2/14 (14.29%)  2 2/6 (33.33%)  2
Nervous system disorders     
Headache  2  5/14 (35.71%)  5 2/6 (33.33%)  2
Dizziness  2  4/14 (28.57%)  4 0/6 (0.00%)  0
Psychiatric disorders     
Insomnia  2  6/14 (42.86%)  6 0/6 (0.00%)  0
Anxiety  2  5/14 (35.71%)  5 1/6 (16.67%)  1
Confusion state  2  3/14 (21.43%)  3 2/6 (33.33%)  2
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  2  6/14 (42.86%)  6 0/6 (0.00%)  0
cough  2  4/14 (28.57%)  4 2/6 (33.33%)  2
Skin and subcutaneous tissue disorders     
Rash  2  5/14 (35.71%)  5 1/6 (16.67%)  1
Vascular disorders     
hypertension  2  4/14 (28.57%)  4 0/6 (0.00%)  0
Hypotension  2  4/14 (28.57%)  4 1/6 (16.67%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE
2
Term from vocabulary, CTCAEv3.0
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: NCT01029366     History of Changes
Obsolete Identifiers: NCT00891215
Other Study ID Numbers: UPCC04409, 809517
NCI-2009-01357
First Submitted: December 9, 2009
First Posted: December 10, 2009
Results First Submitted: June 28, 2016
Results First Posted: February 28, 2017
Last Update Posted: June 26, 2019