Redirected Auto T Cells for Advanced Myeloma

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01352286
• Collaborator: (none)
• Enrollment: 25
• Locations: 2
• Arm: 1
• Actual Duration (Months): 97.8
• Patients Per Site: 12.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to 1) evaluate the safety and tolerability of autologous genetically modified T cells transduced to express the high affinity NY-ESO-1c259 TCR in HLA-A2+ subjects and 2) measure the incidence of GVHD in patients following infusion of TCR modified autologous T cells.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Genetic: Autologous Genetically modified T cells	Phase 2

Detailed Description

The primary objective of this study is to evaluate the safety and tolerability of autologous genetically modified T cells. Genetic material is transferred into the subject's previously harvested autologous T cells to redirect them to target myeloma cells rather than their usual target. Study subjects must have systemic or multifocal myeloma requiring autologous stem cell transplantation whose disease has relapsed or incompletely responded to prior therapy or have high-risk features. Subjects must also have measureable disease on study entry, as defined by quantifiable or detectable levels of serum or urine paraprotein or elevated serum free light chains with an abnormal ratio.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/IIa, Dual-cohort, Two-site, Clinical Trial Evaluating the Safety and Activity of Redirected Autologous T Cells Expressing a High Affinity TCR Specific for NY-ESO-1 Administered Post ASCT in Patients With Advanced Myeloma
• Actual Study Start Date: May 13, 2011
• Actual Primary Completion Date: Aug 25, 2017
• Actual Study Completion Date: Jul 8, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Autologous Genetically modified T cells Patients with advanced myeloma and who are candidates for autologous stem cell transplants, or syngeneic stem cell transplants (SSCT), will be eligible. Prior to full screening on this study, patients will undergo prescreening to evaluate HLA-A type and presence of NY-ESO-1c259T/LAGE antigen. Patients will undergo a steady-state mononuclear cell apheresis for T cell collection, with an optional second collection. Once mononuclear cells have been collected, patients (or donors in the case of SSCT) will then undergo hematopoietic stem cell mobilization. Patients will receive a dose >0.1-1 x 10¹º anti-CD3/anti-CD28-costimulated autologous T cells which have been genetically modified to express high affinity NY-ESO-1c259 TCRs.

Genetic: Autologous Genetically modified T cells; Patients will undergo myeloma restaging at days +42, +100, 6 months, 9 months and 1 year post infusion. At this point, in accordance with FDA Guidelines, all patients will enter long term follow up (LTFU) and be followed biannually for monitoring for gene transfer delayed adverse events until year 5 post infusion. From year 5, all patients will require annual LTFU visits for monitoring for delayed adverse events until year 15 after receiving the genetically modified T cells. Patients whose disease progresses prior to year 1 will enter LTFU at time of progression; however these patients will be seen quarterly from progression until year 1 post infusion and then follow the LTFU schedule mentioned above.

Outcome Measures

Primary Outcome Measures

1. Adverse Events Related to Study Treatment [Day -40 to Year 1 post-treatment]

   Number of Participants with Adverse Events related to study treatment

Secondary Outcome Measures

1. Number of Participants With Response Per International Myeloma Working Group (IMWG) 2011 Criteria [Change from Baseline at Day 42, 100, 180, 270 and Year 1]

   Objective Response Rate (ORR) of sCR (stringent complete response), CR (complete response), VGPR (very good partial response), PR (partial response)

2. Best Objective Response (BOR) [Best Objective Response prior to initiation of lenalidomide and at Year 1]

   Number of participants with Best Objective Response of sCR, CR, VGPR, or PR

3. Duration of Response (DOR), Progression Free Survival (PFS), Overall Survival (OS) [DOR: Initial date of response to date of progressive disease or death PFS: Date of first T -cell infusion to earliest date of disease progression of death due to any cause OS: Date of first T-cell infusion to date of death from any cause.]

   Calculated median DOR, PFS, OS

4. Peak Persistence of Modified T-cells in the Peripheral Blood [Post-infusion through Day 42]

   Measurement of NY-ESO-1ᶜ²⁵⁹T cells in blood

5. Marrow Antigen Expression Pre-and Post-infusion [Pre- and post-infusion]

   Number of participants with NY-ESO-1 and LAGE or LAGE-1a expression in the marrow post-infusion

6. Engraftment of Gene-modified Pentamer+ CD4+ T Cells and CD8+ T Cells [Post Treatment]

   Number of participants with engraftment in blood and bone marrow

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Myeloma has relapsed, progressed, or failed to respond after at least one prior course of therapy (consisting of at least 2 treatment cycles or months of therapy)

• Myeloma has responded partially to initial therapy but a complete response (immunofixation negative and normal serum free light chain) has NOT developed after a minimum of 3 cycles or months of initial therapy

• Myeloma has high-risk features as defined by the presence of one or more cytogenetic abnormalities known to confer a poor outcome even after standard auto-transplants: complex karyotype (≥ to 3 abnormalities), t(4;14), t(14;16), del (17) (p13.1), and/or chromosome 13 abnormalities. These patients may be enrolled even while in complete or near-complete remission

• Measurable disease on study entry, as defined by quantifiable or detectable levels of serum or urine paraprotein or elevated serum free light chains with abnormal ratio

• Patients who are in complete remission at the time of proposed study entry (serum and urine immunofixation consistently negative and normal serum free light chains) are not eligible unless their disease meets the criteria for high-risk as defined in protocol

• Ages 18-80

• ECOG performance status 0-2 (unless due solely to bone pain)

• Prior to Lenalidomide maintenance phase, all study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®

• Females subjects of childbearing potential must have a negative pregnancy test and both male and female (of childbearing potential) subjects must agree to use reliable methods of contraception during the study.

• Lenalidomide treatment phase: able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin)

• HLA-A201 patients must have confirmed expression of NY-ESO-1 and/or LAGE. HLA-A2 patients must have the A-201 allele

Adequate vital organ function as defined below:

• Serum creatinine ≤3.0 mg/dl and not on dialysis

• WBC at least 3000/mm³, platelet count at least 100,000/mm³

• SGOT ≤ to 2 x upper limit of normal and bilirubin ≤ to 2.0 mg/dl (unless due to Gilbert's syndrome)

• Left ventricular ejection fraction (LVEF) ≥ 45%. A lower LVEF is permissible if a formal cardiologic evaluation reveals no evidence for clinically significant functional impairment

• Adequate pulmonary function with mechanical parameters ≥ 40% predicted (FEV1, FVC, TLC, DLCO). Patients who are unable to complete PFTs due to bone pain or fracture must have a high resolution CT scan of the chest and must have acceptable arterial blood gases defined as a room air PO2 greater than 70 mmHg

• Patients should have recovered from any toxicities related to prior therapy or at least returned to their baseline level of organ function.

• Patients should be off of glucocorticoids for at least 2 weeks and/or other therapies for at least 1 week prior to enrollment

Exclusion Criteria:

• Pregnant or nursing females

• HIV or HTLV-1/2 seropositivity

• History of myelodysplasia

• History of chronic active hepatitis or liver cirrhosis (if suspected by laboratory studies, should be confirmed by liver biopsy)

• Active Hepatitis B (as defined by positive Hepatitis B surface antigen); positive Hepatitis C virus (HCV) antibody is NOT an exclusion

• Prior allogeneic transplant

• History of severe autoimmune disease requiring steroids or other immunosuppressive treatments

• Active immune mediated diseases including: connective tissue diseases, uveitis, sarcoidosis, inflammatory bowel disease, multiple sclerosis

• Evidence or history of other significant cardiac, hepatic, renal, ophthalmologic, psychiatric, or gastrointestinal disease which would likely increase the risks of participating in the study

• Active bacterial, viral, or fungal infections

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Baltimore	Maryland	United States	21201
2	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Apr 7, 2017
• Statistical Analysis Plan - Oct 17, 2017

More Information

Publications

• Stadtmauer EA, Faitg TH, Lowther DE, Badros AZ, Chagin K, Dengel K, Iyengar M, Melchiori L, Navenot JM, Norry E, Trivedi T, Wang R, Binder GK, Amado R, Rapoport AP. Long-term safety and activity of NY-ESO-1 SPEAR T cells after autologous stem cell transplant for myeloma. Blood Adv. 2019 Jul 9;3(13):2022-2034. doi: 10.1182/bloodadvances.2019000194.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01352286
• Other Study ID Numbers: 209393; ADP 01411
• First Posted: May 11, 2011
• Last Update Posted: Dec 3, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by GlaxoSmithKline: Multiple myeloma; Received initial treatment previously; Autologous stem cell transplantation
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell

Study Results

Participant Flow

Arm/Group Title	NYESO-1ᶜ²⁵⁹T Cells Administered Intravenously
Arm/Group Description	Participants who received lentivirus-mediated genetically engineered NYESO-1ᶜ²⁵⁹T following autologous stem cell transplantation (ASCT)
Period Title: Overall Study
STARTED	25
Received T-cells	25
COMPLETED	25
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	NYESO-1ᶜ²⁵⁹T Cells
Arm/Group Description	Participants who received NYESO-1ᶜ²⁵⁹T following ASCT
Overall Participants	25
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	17 68%
>=65 years	8 32%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59
Sex: Female, Male (Count of Participants)
Female	10 40%
Male	15 60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	25 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 20%
White	19 76%
More than one race	1 4%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Adverse Events Related to Study Treatment
Description	Number of Participants with Adverse Events related to study treatment
Time Frame	Day -40 to Year 1 post-treatment

Outcome Measure Data

Analysis Population Description

Participants who received NYESO-1ᶜ²⁵⁹T following ASCT

Arm/Group Title	NYESO-1ᶜ²⁵⁹T Cells
Arm/Group Description	Participants who received NYESO-1ᶜ²⁵⁹T following ASCT
Measure Participants	25
Number [participants]	24 96%

2. Secondary Outcome

Title	Number of Participants With Response Per International Myeloma Working Group (IMWG) 2011 Criteria
Description	Objective Response Rate (ORR) of sCR (stringent complete response), CR (complete response), VGPR (very good partial response), PR (partial response)
Time Frame	Change from Baseline at Day 42, 100, 180, 270 and Year 1

Outcome Measure Data

Analysis Population Description

Participants who received NYESO-1ᶜ²⁵⁹T following ASCT

Arm/Group Title	NYESO-1ᶜ²⁵⁹T Cells
Arm/Group Description	Participants who received NYESO-1ᶜ²⁵⁹T following ASCT
Measure Participants	25
Day 42	20 80%
Day 100	19 76%
Day 180	16 64%
Day 270	13 52%
Year 1	11 44%

3. Secondary Outcome

Title	Best Objective Response (BOR)
Description	Number of participants with Best Objective Response of sCR, CR, VGPR, or PR
Time Frame	Best Objective Response prior to initiation of lenalidomide and at Year 1

Outcome Measure Data

Analysis Population Description

Participants who received NYESO-1ᶜ²⁵⁹T following ASCT with Best Objective Response (BOR) data.

Arm/Group Title	NYESO-1ᶜ²⁵⁹T Cells
Arm/Group Description	Participants who received NYESO-1ᶜ²⁵⁹T following ASCT
Measure Participants	25
Prior to Initiation of Lenalidomide : sCR	1 4%
Prior to Initiation of Lenalidomide : CR	0 0%
Prior to Initiation of Lenalidomide : VGPR	12 48%
Prior to Initiation of Lenalidomide : PR	7 28%
Year 1 : sCR	2 8%
Year 1 : CR	1 4%
Year 1 : VGPR	13 52%
Year 1 : PR	5 20%

4. Secondary Outcome

Title	Duration of Response (DOR), Progression Free Survival (PFS), Overall Survival (OS)
Description	Calculated median DOR, PFS, OS
Time Frame	DOR: Initial date of response to date of progressive disease or death PFS: Date of first T -cell infusion to earliest date of disease progression of death due to any cause OS: Date of first T-cell infusion to date of death from any cause.

Outcome Measure Data

Analysis Population Description

Participants who received NYESO-1ᶜ²⁵⁹T following ASCT

Arm/Group Title	NYESO-1ᶜ²⁵⁹T Cells
Arm/Group Description	Participants who received NYESO-1ᶜ²⁵⁹T following ASCT
Measure Participants	25
DOR	12.2
PFS	13.5
OS	35.1

5. Secondary Outcome

Title	Peak Persistence of Modified T-cells in the Peripheral Blood
Description	Measurement of NY-ESO-1ᶜ²⁵⁹T cells in blood
Time Frame	Post-infusion through Day 42

Outcome Measure Data

Analysis Population Description

Participants who received NYESO-1ᶜ²⁵⁹T following ASCT

Arm/Group Title	NYESO-1ᶜ²⁵⁹T Cells
Arm/Group Description	Participants who received NYESO-1ᶜ²⁵⁹T following ASCT
Measure Participants	25
Mean (Full Range) [copies per μg of DNA]	143728.793

6. Secondary Outcome

Title	Marrow Antigen Expression Pre-and Post-infusion
Description	Number of participants with NY-ESO-1 and LAGE or LAGE-1a expression in the marrow post-infusion
Time Frame	Pre- and post-infusion

Outcome Measure Data

Analysis Population Description

Participants who received NYESO-1ᶜ²⁵⁹T following ASCT with expression data at all points.

Arm/Group Title	NYESO-1ᶜ²⁵⁹T Cells
Arm/Group Description	Participants who received NYESO-1ᶜ²⁵⁹T following ASCT with data at pre-and post-infusion time points
Measure Participants	25
Day 100 : NY-ESO-1	16 64%
Day 100 : LAGE or LAGE-1a	16 64%
Day 180 : NY-ESO-1	14 56%
Day 180 : LAGE or LAGE-1a	14 56%

7. Secondary Outcome

Title	Engraftment of Gene-modified Pentamer+ CD4+ T Cells and CD8+ T Cells
Description	Number of participants with engraftment in blood and bone marrow
Time Frame	Post Treatment

Outcome Measure Data

Analysis Population Description

Participants who received NYESO-1ᶜ²⁵⁹T following ASCT with engraftment data.

Arm/Group Title	NYESO-1ᶜ²⁵⁹T Cells
Arm/Group Description	Participants who received NYESO-1ᶜ²⁵⁹T following ASCT
Measure Participants	25
CD4+ : Blood	11 44%
CD4+ : Bone Marrow	11 44%
CD8+ : Blood	11 44%
CD8+ : Bone Marrow	11 44%

Adverse Events

Time Frame	Day -40 to Year 1 post-treatment
Adverse Event Reporting Description	Participants who received NY-ESO-1ᶜ²⁵⁹T following ASCT
Arm/Group Title	NYESO-1ᶜ²⁵⁹T Cells
Arm/Group Description	Participants who received NYESO-1ᶜ²⁵⁹T following ASCT
All Cause Mortality
	NYESO-1ᶜ²⁵⁹T Cells
	Affected / at Risk (%)	# Events
Total	14/25 (56%)
Serious Adverse Events
	NYESO-1ᶜ²⁵⁹T Cells
	Affected / at Risk (%)	# Events
Total	17/25 (68%)
Blood and lymphatic system disorders
Febrile neutropenia	3/25 (12%)	3
Neutropenia	3/25 (12%)	3
Leukopenia	1/25 (4%)	1
Cardiac disorders
Atrial fibrillation	3/25 (12%)	3
Gastrointestinal disorders
Hypoxia	2/25 (8%)	2
Colitis	1/25 (4%)	1
Graft versus host disease in gastrointestinal tract	1/25 (4%)	1
General disorders
Pyrexia	3/25 (12%)	3
Asthenia	1/25 (4%)	1
Immune system disorders
Graft versus host disease	2/25 (8%)	2
Autoimmune disorder	1/25 (4%)	1
Infections and infestations
Staphylococcal infection	2/25 (8%)	2
Hepatic infection	1/25 (4%)	1
Influenza	1/25 (4%)	1
Klebsiella infection	1/25 (4%)	1
Neutropenic sepsis	1/25 (4%)	1
Viral upper respiratory tract infection	1/25 (4%)	1
Injury, poisoning and procedural complications
Hip Fracture	1/25 (4%)	1
Investigations
Blood creatine phosphokinase increased	1/25 (4%)	1
Blood lactate dehydrogenase increased	1/25 (4%)	1
Ejection Fraction	1/25 (4%)	1
Myoglobin blood	1/25 (4%)	1
Myoglobin urine	1/25 (4%)	1
Neutrophil count decreased	1/25 (4%)	1
Platelet count decreased	1/25 (4%)	1
Metabolism and nutrition disorders
Dehydration	1/25 (4%)	1
Failure to Thrive	1/25 (4%)	1
Hypercalcaemia	1/25 (4%)	1
Hyponatraemia	1/25 (4%)	1
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	1/25 (4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasmacytoma	1/25 (4%)	1
Nervous system disorders
Syncope	1/25 (4%)	1
Renal and urinary disorders
Acute Kidney Injury	1/25 (4%)	1
Hydronephrosis	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/25 (4%)	1
Dyspnea	1/25 (4%)	1
Pneumonitis	1/25 (4%)	1
Pulmonary edema	1/25 (4%)	1
Vascular disorders
Deep vein thrombosis	1/25 (4%)	1
Hypotension	1/25 (4%)	1
Other (Not Including Serious) Adverse Events
	NYESO-1ᶜ²⁵⁹T Cells
	Affected / at Risk (%)	# Events
Total	25/25 (100%)
Blood and lymphatic system disorders
Anaemia	24/25 (96%)	24
Thrombocytopenia	18/25 (72%)	18
Febrile neutropenia	16/25 (64%)	16
Leukopenia	2/25 (8%)	2
Neutropenia	8/25 (32%)	8
Cardiac disorders
Tachycardia	6/25 (24%)	6
Sinus tachycardia	5/25 (20%)	5
Atrial fibrillation	3/25 (12%)	3
Palpitations	2/25 (8%)	2
Ventricular tachycardia	2/25 (8%)	2
Eye disorders
Vision blurred	2/25 (8%)	2
Gastrointestinal disorders
Nausea	25/25 (100%)	25
Diarrhea	24/25 (96%)	24
Vomiting	19/25 (76%)	19
Stomatitis	14/25 (56%)	14
Abdominal pain	13/25 (52%)	13
Constipation	12/25 (48%)	12
Oral Pain	7/25 (28%)	7
Abdominal distension	4/25 (16%)	4
Oesophagitis	4/25 (16%)	4
Dry Mouth	3/25 (12%)	3
Mouth ulceration	3/25 (12%)	3
Neutropenic colitis	3/25 (12%)	3
Oral dysaesthesia	3/25 (12%)	3
Abdominal tenderness	2/25 (8%)	2
Dysphagia	2/25 (8%)	2
Gastroesophageal reflux disease	2/25 (8%)	2
General disorders
Fatigue	22/25 (88%)	22
Pyrexia	20/25 (80%)	20
Oedema peripheral	14/25 (56%)	14
Chills	10/25 (40%)	10
Pain	7/25 (28%)	7
Localized edema	5/25 (20%)	5
Mucosal inflammation	4/25 (16%)	4
Catheter site pain	3/25 (12%)	3
Malaise	3/25 (12%)	3
Catheter site discharge	2/25 (8%)	2
Catheter site hemorrhage	2/25 (8%)	2
Chest discomfort	2/25 (8%)	2
Face edema	2/25 (8%)	2
Peripheral swelling	2/25 (8%)	2
Immune system disorders
Graft Versus Host Disease (GVHD)	4/25 (16%)	4
Autoimmune disorder	3/25 (12%)	3
Infections and infestations
Upper respiratory tract infection	11/25 (44%)	11
Candida infection	5/25 (20%)	5
Herpes zoster	4/25 (16%)	4
Clostridium difficile infection	3/25 (12%)	3
Oral candidiasis	3/25 (12%)	3
Pneumonia	3/25 (12%)	3
Clostridium difficile colitis	2/25 (8%)	2
Diverticulitis	2/25 (8%)	2
Sinusitis	2/25 (8%)	2
Staphylococcal infection	2/25 (8%)	2
Tooth abscess	2/25 (8%)	2
Tooth infection	2/25 (8%)	2
Viral upper respiratory tract infection	2/25 (8%)	2
Injury, poisoning and procedural complications
Contusion	2/25 (8%)	2
Fall	2/25 (8%)	2
Investigations
Platelet count decreased	12/25 (48%)	12
WBC decreased	13/25 (52%)	13
Neutrophil count decreased	8/25 (32%)	8
Alanine aminotransferase increased	6/25 (24%)	6
Blood alkaline phosphatase increased	5/25 (20%)	5
Lymphocyte count decreased	5/25 (20%)	5
Aspartate aminotransferase increased	4/25 (16%)	4
Blood creatinine increased	4/25 (16%)	4
Weight decreased	4/25 (16%)	4
Blood creatinine decreased	3/25 (12%)	3
Blood bilirubin increased	2/25 (8%)	2
International normalized ratio increased	2/25 (8%)	2
Metabolism and nutrition disorders
Decreased appetite	23/25 (92%)	23
Hypokalemia	19/25 (76%)	19
Hypocalcaemia	14/25 (56%)	14
Hyperglycemia	12/25 (48%)	12
Hypomagnesaemia	12/25 (48%)	12
Hypophosphataemia	12/25 (48%)	12
Hypoalbuminaemia	8/25 (32%)	8
Hyponatraemia	7/25 (28%)	7
Hypoglycemia	4/25 (16%)	4
Hyperkalaemia	3/25 (12%)	3
Hypernatraemia	3/25 (12%)	3
Dehydration	2/25 (8%)	2
Hypercalcaemia	2/25 (8%)	2
Hypermagnesaemia	2/25 (8%)	2
Malnutrition	2/25 (8%)	2
Musculoskeletal and connective tissue disorders
Back pain	15/25 (60%)	15
Muscular weakness	12/25 (48%)	12
Pain in extremity	9/25 (36%)	9
Arthralgia	6/25 (24%)	6
Musculoskeletal chest pain	6/25 (24%)	6
Neck Pain	6/25 (24%)	6
Flank pain	4/25 (16%)	4
Muscle spasms	4/25 (16%)	4
Musculoskeletal pain	3/25 (12%)	3
Myalgia	3/25 (12%)	3
Joint range of motion decreased	2/25 (8%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasmacytoma	2/25 (8%)	2
Nervous system disorders
Headache	11/25 (44%)	11
Dizziness	6/25 (24%)	6
Peripheral sensory neuropathy	5/25 (20%)	5
Paresthesia	4/25 (16%)	4
Dysgeusia	3/25 (12%)	3
Neuralgia	3/25 (12%)	3
Peripheral motor neuropathy	3/25 (12%)	3
Tremor	3/25 (12%)	3
Neuropathy peripheral	2/25 (8%)	2
Sinus headache	2/25 (8%)	2
Psychiatric disorders
Insomnia	8/25 (32%)	8
Anxiety	6/25 (24%)	6
Depression	4/25 (16%)	4
Confusional state	3/25 (12%)	3
Agitation	2/25 (8%)	2
Delirium	2/25 (8%)	2
Renal and urinary disorders
Acute kidney injury	3/25 (12%)	3
Haematuria	2/25 (8%)	2
Renal failure	2/25 (8%)	2
Urinary incontinence	2/25 (8%)	2
Respiratory, thoracic and mediastinal disorders
Cough	14/25 (56%)	14
Dyspnea	13/25 (52%)	13
Oropharyngeal pain	8/25 (32%)	8
Hiccups	3/25 (12%)	3
Rales	3/25 (12%)	3
Tachypnoea	3/25 (12%)	3
Wheezing	3/25 (12%)	3
Dyspnea exertional	2/25 (8%)	2
Pneumonitis	2/25 (8%)	2
Productive cough	2/25 (8%)	2
Sinus pain	2/25 (8%)	2
Skin and subcutaneous tissue disorders
Rash maculo-papular	20/25 (80%)	20
Erythema multiforme	2/25 (8%)	2
Alopecia	4/25 (16%)	4
Pruritus	4/25 (16%)	4
Hyperhidrosis	3/25 (12%)	3
Dry skin	2/25 (8%)	2
Ecchymosis	2/25 (8%)	2
Erythema	2/25 (8%)	2
Palmar-plantar erythrodysaesthesia syndrome	2/25 (8%)	2
Petechiae	2/25 (8%)	2
Purpura	2/25 (8%)	2
Scab	2/25 (8%)	2
Skin disorder	2/25 (8%)	2
Skin ulcer	2/25 (8%)	2
Vascular disorders
Hypotension	9/25 (36%)	9
Hypertension	4/25 (16%)	4
Flushing	2/25 (8%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.