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

Sponsor
University of Pennsylvania (Other)
Overall Status
Completed
CT.gov ID
NCT01626495
Collaborator
(none)
73
1
1
94.8
0.8

Study Details

Study Description

Brief Summary

This is a study for children who have been previously treated for Leukemia/Lymphoma. In particular, it is a study for people who have a type of Leukemia/Lymphoma that involves B cells (a type of white cell), which contain the cancer. This is a new approach for treatment of Leukemia/Lymphoma that involves B cells (tumor cells). This study will take the subject's white blood cells (T cells) and modify them in order to target the cancer.

The subject's 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). Both ways of modifying the cells tells the T cells to go to the B cells (tumor cells) and turn "on" and potentially kill the B cells (tumor cells). The modification is a genetic change to the T cells, or gene transfer, in order to allow the modified T cells to recognize your tumor cells but not other normal cells in the subject's body. These modified cells are called chimeric antigen receptor 19 (CART19) T-cells.

Condition or Disease Intervention/Treatment Phase
  • Biological: CART-19
Phase 1/Phase 2

Detailed Description

At entry subjects will be staged and the suitability of their T cells for CART-19 manufacturing will be determined. Subjects who have adequate T cells will be leukapheresed to obtain large numbers of peripheral blood mononuclear cells (PBMC) for CART-19 manufacturing. The T cells will be purified from the PBMC, transduced with CART-19 lentiviral vector, expanded in vitro and then frozen for future administration. Chemotherapy will then be given. Following tumor burden reassessment, CART-19 cells will be thawed and infused.

Subjects will have blood tests to assess safety, and engraftment and persistence of the CART-19 cells at regular intervals through four weeks after their last infusion of the study. Following the 6 months of intensive follow-up, subjects will be evaluated quarterly for two years with a medical history, a physical examination, and blood tests. Following this evaluation, subjects will enter a roll-over study for annual follow-up by phone and questionnaire for an additional thirteen years to assess for the diagnosis of long-term health problems, such as development of new malignancy.

Primary objectives:
  1. Determine the safety and feasibility of administration of chimeric antigen receptor T cells transduced with the anti-CD 19 lentiviral vector (referred to as "CART-19" cells).

  2. Determine duration of in vivio survival of CART-19 cells. Real Time polymerase chain receptor (RT-PCR) analysis of whole blood will be used to detect and quantify survival of CART-19 TCR:4-1BB and TCR cells over time.

Secondary objectives:
  1. For patients with detectable disease, measure anti-tumor response due to CART-19 cell infusions.

  2. To determine if the 4-1BB transgene is superior to the TCR only transgene as measured by the relative engraftment levels of CART-19 TCR:4-1BB and TCR cells over time.

  3. For patients with stored or accessible tumor cells (such as patients with active chronic lymphocytic leukemia (CLL), acute lymphoblastic leukema (ALL), etc) determine tumor cell killing by CART-19 cells in vitro.

  4. Determine if cellular or humoral host immunity develops against the murine anti-CD19, and assess correlation with loss of detectable CART-19 (loss of engraftment).

  5. Determine the relative subsets of CART-19 T cells (Tcm, Tem, and Treg)

Study Design

Study Type:
Interventional
Actual Enrollment :
73 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
CHP 959 - A Phase I/IIA Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCRzeta and 4-1BB Signaling Domains in Patients With Chemotherapy Resistant Or Refractory CD19+ Leukemia and Lymphoma
Actual Study Start Date :
Aug 17, 2011
Actual Primary Completion Date :
May 7, 2018
Actual Study Completion Date :
Jul 11, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: CART-19 T Cells

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.

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

Outcome Measures

Primary Outcome Measures

  1. Number of Subjects With Study Related Adverse Events. [24 weeks]

    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.

Secondary Outcome Measures

  1. The Number of Subjects With a Successful Product Manufactured [24 weeks]

  2. Number of Subjects With Complete Remission (CR). [4 Weeks]

    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.

  3. Number of Subjects With Complete Remission With Incomplete Blood Count Recovery (CRi). [4 Weeks]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
1 Year to 24 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

Male and female subjects with CD 19+ B cell malignancies in patients with no available curative treatment options (such as autologous or allogeneic SCT) who have limited prognosis (several months to <2 year survival) with currently available therapies will be enrolled:

  1. Eligible diseases: CD 19+ leukemia or lymphoma

  2. ALL without curative options for therapy, including those not eligible for allogeneic

SCT because of:
  • age

  • co-morbid disease

  • other contraindications to TBI-based conditioning (required for ALL SCT)

  • lack of suitable donor

  • prior SCT

  • Declines allo SCT (in CR3) as a therapeutic option after documented discussion about the role of SCT with a BMT physician not part of the study team. Note: Patient may be in any complete response, or patient may have active disease but responding or stable after most recent therapy. The intent is not to enroll patients with no degree of disease control, or rapidly increasing disease burden between enrollment and cell infusion.

  1. Follicular lymphoma, previously identified as CD19+
  • At least 2 prior combination chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy.

  • Stage III-IV disease.

  • Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval <1 year).

  • Disease responding or stable after most recent therapy (chemotherapy, MoAb).

  1. CLL
  • At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy.

  • Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval <1 year).

  • Not eligible or appropriate for conventional allogeneic SCT

  • Disease responding or stable after most recent therapy (chemotherapy, MoAb)

  1. Mantle cell lymphoma
  • Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT

  • Disease responding or stable after most recent therapy (chemotherapy, MoAb)

  • Relapsed after prior autologous SCT

  1. B-cell prolymphocytic leukemia (PLL) with relapsed or residual disease after at least 1 prior therapy and not eligible for allogeneic SCT.

  2. Diffuse large cell lymphoma or other high-grade NHL, previously identified as CD19+

  • Residual disease after primary therapy and not eligible for autologous SCT

  • Relapsed after prior autologous SCT

  • Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT

  1. Age 1 to 24 years. Patients ages 22-24 will only be enrolled if they are currently being treated at CHOP or another pediatric facility/oncologist

  2. Expected survival > 12 weeks

  3. Creatinine < 2.5 mg/dl and less than 2.5x normal for age

  4. ALT ≤ 5x normal

  5. Bilirubin <2.0 mg/dl

  6. Any relapse after prior SCT will make patient eligible regardless of other prior therapy

  7. Patients with relapsed disease after prior allogeneic SCT (myeloablative or non-myeloablative) will be eligible if they meet all other inclusion criteria and

  8. Have no active GVHD and require no immunosuppression

  9. Are more than 4 months from transplant

  10. For those patients who require leukapheresis for T cell collection (i.e. no previously collected product exists), adequate venous access for apheresis or eligible for appropriate catheter placement, and no other contraindications for leukapheresis

  11. Voluntary informed consent is given

  12. Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy (at infusion)

Exclusion Criteria:
  1. Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion

  2. Uncontrolled active infection

  3. Active hepatitis B or hepatitis C infection

  4. Concurrent use of systemic steroids at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of inhaled steroids, or hydrocortisone for physiological replacement in patients with adrenal insufficiency are permitted as well

  5. Presence of grade 2-4 acute or extensive chronic GVHD

  6. Under treatment for GVHD

  7. Previous treatment with any gene therapy products

  8. Any uncontrolled active medical disorder that would preclude participation as outlined.

  9. HIV infection.

  10. CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity

Contacts and Locations

Locations

Site City State Country Postal Code
1 CHOP - http://www.chop.edu/service/oncology/pediatric-cancer-research/cart-19-trial.html Philadelphia Pennsylvania United States 19104

Sponsors and Collaborators

  • University of Pennsylvania

Investigators

  • Principal Investigator: Stephan A Grupp, MD,PhD, Children's Hospital of Philadelphia

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01626495
Other Study ID Numbers:
  • 10-007706, 815870
  • CHP959
First Posted:
Jun 22, 2012
Last Update Posted:
Mar 23, 2020
Last Verified:
Mar 1, 2020
Keywords provided by University of Pennsylvania
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title CART-19 T Cells
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
Intervention 62
COMPLETED 21
NOT COMPLETED 52

Baseline Characteristics

Arm/Group Title CART-19 T Cells
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 Participants 62
Age (Count of Participants)
<=18 years
54
87.1%
Between 18 and 65 years
8
12.9%
>=65 years
0
0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
12
(5.25)
Sex: Female, Male (Count of Participants)
Female
28
45.2%
Male
34
54.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
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%
Unknown or Not Reported
2
3.2%
Region of Enrollment (participants) [Number]
United States
62
100%

Outcome Measures

1. Primary Outcome
Title Number of Subjects With Study Related Adverse Events.
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

Outcome Measure Data

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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title CART-19 T Cells
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.
Measure Participants 62
Count of Participants [Participants]
60
96.8%
3. Secondary Outcome
Title Number of Subjects With Complete Remission (CR).
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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title CART-19 T Cells
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.
Measure Participants 62
Count of Participants [Participants]
16
25.8%
4. Secondary Outcome
Title Number of Subjects With Complete Remission With Incomplete Blood Count Recovery (CRi).
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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title CART-19 T Cells
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.
Measure Participants 62
Count of Participants [Participants]
38
61.3%

Adverse Events

Time Frame 2 Years
Adverse Event Reporting Description
Arm/Group Title CART-19 T Cells
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 (%) # Events
Total 2/73 (2.7%)
Serious Adverse Events
CART-19 T Cells
Affected / at Risk (%) # Events
Total 58/73 (79.5%)
Blood and lymphatic system disorders
Febrile neutropenia 46/73 (63%)
Disseminated intravascular coagulation 6/73 (8.2%)
Coagulopathy 3/73 (4.1%)
Hypofibrinogenaemia 1/73 (1.4%)
Haemolysis 1/73 (1.4%)
Cardiac disorders
Left ventricular dysfunction 4/73 (5.5%)
Bradycardia 1/73 (1.4%)
Cardio-respiratory arrest 1/73 (1.4%)
Atrial thrombosis 1/73 (1.4%)
Endocrine disorders
Adrenal insufficiency 1/73 (1.4%)
Eye disorders
Visual impairment 1/73 (1.4%)
Gastrointestinal disorders
Abdominal pain 1/73 (1.4%)
Haematochezia 1/73 (1.4%)
Vomiting 2/73 (2.7%)
Nausea 1/73 (1.4%)
General disorders
Pyrexia 15/73 (20.5%)
Vascular stent thrombosis 1/73 (1.4%)
Facial pain 1/73 (1.4%)
Pain 3/73 (4.1%)
Complication associated with device 1/73 (1.4%)
Immune system disorders
Cytokine release syndrome 52/73 (71.2%)
Anaphylactic reaction 1/73 (1.4%)
Infections and infestations
Device related infection 5/73 (6.8%)
Lung infection 1/73 (1.4%)
Staphylococcal infection 1/73 (1.4%)
Streptococcal infection 1/73 (1.4%)
Varicella zoster virus infection 1/73 (1.4%)
Bk virus infection 1/73 (1.4%)
Enterococcal bacteraemia 1/73 (1.4%)
Gastroenteritis salmonella 1/73 (1.4%)
Klebsiella infection 1/73 (1.4%)
Stomatococcal infection 1/73 (1.4%)
Pyomyositis 1/73 (1.4%)
Staphylococcal skin infection 1/73 (1.4%)
Staphylococcal bacteraemia 1/73 (1.4%)
Clostridium difficile colitis 1/73 (1.4%)
Injury, poisoning and procedural complications
Thermal burn 1/73 (1.4%)
Transfusion reaction 1/73 (1.4%)
Lower limb fracture 1/73 (1.4%)
Investigations
Weight decreased 1/73 (1.4%)
Metabolism and nutrition disorders
Dehydration 5/73 (6.8%)
Decreased appetite 1/73 (1.4%)
Hyperkalaemia 1/73 (1.4%)
Hypokalaemia 1/73 (1.4%)
Tumour lysis syndrome 1/73 (1.4%)
Acidosis 1/73 (1.4%)
Musculoskeletal and connective tissue disorders
Pain in extremity 1/73 (1.4%)
Bone pain 1/73 (1.4%)
Arthralgia 1/73 (1.4%)
Nervous system disorders
Encephalopathy 17/73 (23.3%)
Seizure 4/73 (5.5%)
Generalised tonic-clonic seizure 1/73 (1.4%)
Headache 3/73 (4.1%)
Speech disorder 1/73 (1.4%)
Unresponsive to stimuli 1/73 (1.4%)
Central nervous system haemorrhage 1/73 (1.4%)
Facial paresis 1/73 (1.4%)
Psychiatric disorders
Mental status changes 1/73 (1.4%)
Confusional state 1/73 (1.4%)
Renal and urinary disorders
Acute kidney injury 5/73 (6.8%)
Respiratory, thoracic and mediastinal disorders
Hypoxia 10/73 (13.7%)
Acute respiratory distress syndrome 4/73 (5.5%)
Apnoea 1/73 (1.4%)
Epistaxis 1/73 (1.4%)
Pleural effusion 1/73 (1.4%)
Respiratory alkalosis 1/73 (1.4%)
Respiratory distress 1/73 (1.4%)
Respiratory failure 1/73 (1.4%)
Acute respiratory failure 1/73 (1.4%)
Asthma 1/73 (1.4%)
Aspiration 1/73 (1.4%)
Vascular disorders
Hypotension 24/73 (32.9%)
Capillary leak syndrome 10/73 (13.7%)
Hypertension 1/73 (1.4%)
Other (Not Including Serious) Adverse Events
CART-19 T Cells
Affected / at Risk (%) # Events
Total 62/73 (84.9%)
Blood and lymphatic system disorders
Febrile neutropenia 10/73 (13.7%)
Lymphopenia 50/73 (68.5%)
Splenomegaly 5/73 (6.8%)
Anaemia 3/73 (4.1%)
Cardiac disorders
Sinus tachycardia 12/73 (16.4%)
Tachycardia 30/73 (41.1%)
Eye disorders
Conjunctival haemorrhage 4/73 (5.5%)
Diplopia 4/73 (5.5%)
Photophobia 4/73 (5.5%)
Vision blurred 3/73 (4.1%)
Gastrointestinal disorders
Abdominal pain 21/73 (28.8%)
Constipation 10/73 (13.7%)
Diarrhoea 35/73 (47.9%)
Haematochezia 4/73 (5.5%)
Nausea 45/73 (61.6%)
Vomiting 48/73 (65.8%)
Gingival bleeding 3/73 (4.1%)
Mouth haemorrhage 3/73 (4.1%)
General disorders
Chills 27/73 (37%)
Fatigue 29/73 (39.7%)
Pain 28/73 (38.4%)
Pyrexia 15/73 (20.5%)
Catheter site haemorrhage 3/73 (4.1%)
Catheter site pain 3/73 (4.1%)
Complication associated with device 3/73 (4.1%)
Face oedema 3/73 (4.1%)
Generalised oedema 3/73 (4.1%)
Withdrawal syndrome 3/73 (4.1%)
Hepatobiliary disorders
Hepatomegaly 5/73 (6.8%)
Hyperbilirubinaemia 13/73 (17.8%)
Immune system disorders
Cytokine release syndrome 5/73 (6.8%)
Hypogammaglobulinaemia 42/73 (57.5%)
Seasonal allergy 3/73 (4.1%)
Infections and infestations
Otitis media 6/73 (8.2%)
Pneumonia 4/73 (5.5%)
Respiratory syncytial virus infection 4/73 (5.5%)
Sinusitis 10/73 (13.7%)
Upper respiratory tract infection 11/73 (15.1%)
Urinary tract infection 4/73 (5.5%)
Clostridium difficile colitis 3/73 (4.1%)
Escherichia urinary tract infection 3/73 (4.1%)
Oral candidiasis 3/73 (4.1%)
Rhinitis 3/73 (4.1%)
Injury, poisoning and procedural complications
Contusion 7/73 (9.6%)
Fall 4/73 (5.5%)
Infusion related reaction 4/73 (5.5%)
Procedural pain 11/73 (15.1%)
Transfusion reaction 3/73 (4.1%)
Investigations
Activated partial thromboplastin time prolonged 22/73 (30.1%)
Alanine aminotransferase increased 45/73 (61.6%)
Aspartate aminotransferase increased 46/73 (63%)
Blood bilirubin increased 15/73 (20.5%)
Blood creatinine increased 23/73 (31.5%)
Blood fibrinogen decreased 11/73 (15.1%)
Blood immunoglobulin A decreased 5/73 (6.8%)
Blood immunoglobulin M decreased 5/73 (6.8%)
Blood uric acid increased 11/73 (15.1%)
Haemoglobin decreased 57/73 (78.1%)
International normalised ratio increased 16/73 (21.9%)
Lipase increased 4/73 (5.5%)
Lymphocyte count decreased 6/73 (8.2%)
Neutrophil count decreased 56/73 (76.7%)
Platelet count decreased 54/73 (74%)
Weight decreased 5/73 (6.8%)
White blood cell count decreased 58/73 (79.5%)
Amylase increased 3/73 (4.1%)
Prothrombin time prolonged 3/73 (4.1%)
Metabolism and nutrition disorders
Decreased appetite 43/73 (58.9%)
Hyperglycaemia 7/73 (9.6%)
Hyperphosphataemia 22/73 (30.1%)
Hyperuricaemia 8/73 (11%)
Hypocalcaemia 10/73 (13.7%)
Hypokalaemia 11/73 (15.1%)
Hyponatraemia 6/73 (8.2%)
Hypophosphataemia 15/73 (20.5%)
Metabolic acidosis 8/73 (11%)
Dehydration 3/73 (4.1%)
Hypernatraemia 3/73 (4.1%)
Hypoglycaemia 3/73 (4.1%)
Musculoskeletal and connective tissue disorders
Arthralgia 9/73 (12.3%)
Back pain 5/73 (6.8%)
Myalgia 14/73 (19.2%)
Neck pain 4/73 (5.5%)
Pain in extremity 14/73 (19.2%)
Pain in jaw 4/73 (5.5%)
Joint range of motion decreased 3/73 (4.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma 3/73 (4.1%)
Nervous system disorders
Dizziness 12/73 (16.4%)
Headache 46/73 (63%)
Tremor 4/73 (5.5%)
Product Issues
Device occlusion 4/73 (5.5%)
Psychiatric disorders
Anxiety 5/73 (6.8%)
Confusional state 15/73 (20.5%)
Insomnia 8/73 (11%)
Depression 3/73 (4.1%)
Irritability 3/73 (4.1%)
Renal and urinary disorders
Haematuria 4/73 (5.5%)
Acute kidney injury 3/73 (4.1%)
Dysuria 3/73 (4.1%)
Reproductive system and breast disorders
Rhinorrhoea 16/73 (21.9%)
Respiratory, thoracic and mediastinal disorders
Cough 35/73 (47.9%)
Dyspnoea 4/73 (5.5%)
Epistaxis 15/73 (20.5%)
Hypoxia 9/73 (12.3%)
Nasal congestion 13/73 (17.8%)
Oropharyngeal pain 6/73 (8.2%)
Pleural effusion 6/73 (8.2%)
Tachypnoea 10/73 (13.7%)
Pulmonary oedema 3/73 (4.1%)
Rhinitis allergic 3/73 (4.1%)
Skin and subcutaneous tissue disorders
Dermatitis 4/73 (5.5%)
Petechiae 9/73 (12.3%)
Pruritus generalised 6/73 (8.2%)
Rash 8/73 (11%)
Rash erythematous 6/73 (8.2%)
Rash papular 8/73 (11%)
Skin lesion 6/73 (8.2%)
Dry skin 3/73 (4.1%)
Eczema 3/73 (4.1%)
Vascular disorders
Hypertension 13/73 (17.8%)
Hypotension 13/73 (17.8%)

Limitations/Caveats

[Not Specified]

More Information

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

Name/Title Regulatory Lead
Organization University of Pennsylvania
Phone 215-662-4484
Email psom-ind-ide@pobox.upenn.edu
Responsible Party:
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01626495
Other Study ID Numbers:
  • 10-007706, 815870
  • CHP959
First Posted:
Jun 22, 2012
Last Update Posted:
Mar 23, 2020
Last Verified:
Mar 1, 2020