First Autologous Transplant on Minimal Residual Disease Markers in Previously Untreated Myeloma Undergoing Initial Treatment With Velcade

• Sponsor: Vanderbilt-Ingram Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01215344
• Collaborator: (none)
• Enrollment: 36
• Locations: 2
• Arms: 2
• Duration (Months): 88
• Patients Per Site: 18
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to study the MRD status after VELCADE based induction therapy (VELCADE, lenalidomide, dexamethasone or VELCADE, liposomal doxorubicin, dexamethasone) in patients with previously untreated multiple myeloma and study the impact of HDC and ASCT on MRD status post-transplant. Our hypothesis is that MRD-status will continue to increase significantly at 3 months post-transplant and will validate that HDC and ASCT needs to be performed even when patients have achieved major response after induction therapy with novel agents.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: VELCADE; Drug: Lenalidomide; Drug: Dexamethasone; Drug: DVT prophylaxis; Drug: Bisphosphonates; Drug: Liposomal doxorubicin; Drug: Dexamethasone	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Impact of First Autologous Transplant on Minimal Residual Disease Markers in Previously Untreated Myeloma Undergoing Initial Treatment With Velcade Based Therapy
• Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Mar 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VRD VELCADE, Lenalidomide, Dexamethasone	Drug: VELCADE; 1.3 mg/m2 by IV on days 1, 4, 8, 11 of each cycle; Drug: Lenalidomide; 25 mg by mouth on days 1-4 of each cycle; Drug: Dexamethasone; 20 mg the day before and the day after receiving VELCADE; Drug: DVT prophylaxis; At least one asprin 81 mg per day. Other option per physician's choice; Drug: Bisphosphonates; Zoledronic acid by IB or pamidronate by IV can be used as per standard of care.
Experimental: VDD VELCADE, liposomal doxorubicin, dexamethasone	Drug: VELCADE; 1.3 mg/m2 by IV on days 1, 4, 8, 11 of each cycle; Drug: DVT prophylaxis; At least one asprin 81 mg per day. Other option per physician's choice; Drug: Liposomal doxorubicin; 30 mg/m2 on day 4 of each cycle; Drug: Dexamethasone; 40 mg by mouth on days 1-4, 8-11, and 15-18 of cycle 1 and days 1-4 on cycle 2-4

Outcome Measures

Primary Outcome Measures

1. The Percent of Patients With Minimal Residual Disease (MRD) Status Changing to Negative at Day 100 (Post-AHCT), Among Patients With MRD Positive at the End of Induction (EOI). [6-months post ASCT]

   Patients were treated with induction therapy (VRD) followed by autologous hematopoietic cell transplant (AHCT). MRD status of a patient with at least partial response was evaluated at the end of induction (EOI) and day 100 (post-AHCT). MRD of a patient is measured by seven-color flow cytometry.

Secondary Outcome Measures

1. Progression Free Survival by MRD Status at Day 100. [up to 7 years]

   Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Confirmed Multiple Myeloma as defined below within 120 days of starting cycle 1:

• Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells or biopsy proven plasmacytoma

• Presence of M protein in serum or urine or both. Conventional M spike, serum free light chains, or 24 hour urine study. Non-secretory myeloma is not eligible for this study.

• In addition patient must have one of the following organ dysfunction criteria

• Hypercalcemia

• Renal insufficiency

• Anemia

• Bone disease manifested by lytic lesion or osteoporosis (if osteoporosis is the only organ dysfunction criteria then BM should have ≥ 30% plasma cells)

• Confirmed Multiple myeloma as defined above within 90 days of starting cycle 1

• The following study assessments must be fulfilled and must be obtained with four weeks of starting cycle 1

• Hemoglobin > 7 g/dL, Platelet count > 75 X 10 to 9th power/L, and Absolute neutrophil count > 1 X 10 to 9th power/L

• Creatinine <2.5 mg/dL or calculated creatinine clearance > 30 ml/min/1.72 m2

• Bilirubin ≤ 1.5 mg/dL X ULN

• SGPT (ALT) and SGOT (AST) ≤ 2.5 times the upper limit of normal

• Ejection fraction ≥ 45% as measured by a MUGA scan or 2 D echocardiogram

• Pulmonary function tests show >60% predicted values for FVC, FEV1, and DLCO FEV1 must be > 1 liter.

• No prior systemic therapy with the exception of bisphosphonates for MM

• Prior glucocorticoid therapy for the treatment of multiple myeloma is not permitted EXCEPT if used in conjunction with palliative radiation to prevent vasogenic edema. In that case steroids should have been used for less than 7 days. Prior steroid use for non-malignant disorders is permitted and should have been restricted to less than the equivalent of prednisone 10 mg per day. Prior or concurrent topical or localized steroid therapy to treat non-malignant disorders is permitted

• Prior palliative and/ or localized radiation therapy is permitted provided at least 4 weeks have passed from date of last radiation therapy to starting cycle 1.

• Patients with prior solitary plasmacytoma treated with radiation therapy with curative intent are eligible if the disease has now progressed to active multiple myeloma and meeting all eligibility criteria for the protocol

• ECOG PS 0, 1 or 2

• For women of childbearing potential a negative serum pregnancy test is required within 4 weeks of starting cycle 1 and then every 4 weeks during the first 4 cycles of induction therapy

• Women of child bearing potential must be willing to refrain from sexual intercourse or willing to employ a dual method of contraception, one of which is highly effective (IUD, birth control pills, tubal ligation or partner's vasectomy) and another additional method (condom, diaphragm, or cervical cap) during the entire course of the study (start of therapy until 30 days after stem cell transplant).

• Sexually active males should be willing to use a condom (even if they have had a prior vasectomy) while having intercourse with any women during the course of the study (start of therapy until 30 days after stem cell transplant).

• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Exclusion Criteria:

• Patients with smoldering myeloma or monoclonal gammopathy of unknown significance are not eligible

• Age > 70 years or < 18 years is not eligible

• Patient has > 1.5 × ULN Total Bilirubin

• Grade 2 or higher peripheral neuropathy due to ANY cause

• High index of suspicion of primary amyloid light chain (AL) amyloidosis.

• Patients with uncontrolled inter-current illness including uncontrolled hypertension, symptomatic congestive heart failure, unstable angina, uncontrolled cardiac arrhythmia, uncontrolled psychiatric illness or social situation that would limit compliance or a prior history of Steven Johnson syndrome

• Patients must not have a history of current or previous deep vein thrombosis or pulmonary embolism regardless of whether or not the patient is receiving anticoagulation therapy

• Female patients who are breastfeeding or pregnant.

• Patients known to be HIV positive

• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 31.3), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.

• Patient has hypersensitivity to VELCADE, boron or mannitol.

• Patient has received other investigational drugs within 14 days before enrollment

• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Tennessee Cancer Institute, Boston Baskin Cancer Group	Memphis	Tennessee	United States	38104
2	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Vanderbilt-Ingram Cancer Center

Investigators

• Principal Investigator: Madan Jagasia, MD, Vanderbilt-Ingram Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

Publications

None provided.

• Responsible Party: Madan Jagasia, MD, Associate Professor of Medicine; Director, Outpatient Transplant Program; Section Chief, Hematology and Stem Cell Transplant; Hematologist/Oncologist, Vanderbilt-Ingram Cancer Center
• ClinicalTrials.gov Identifier: NCT01215344
• Other Study ID Numbers: VICC BMT 1020
• First Posted: Oct 6, 2010
• Last Update Posted: May 15, 2018
• Last Verified: Apr 1, 2018

• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasm, Residual; Diphosphonates; Dexamethasone; Dexamethasone acetate; Doxorubicin; Liposomal doxorubicin; Lenalidomide; Bortezomib; BB 1101

Study Results

Participant Flow

Recruitment Details	Participants participated in this trial at Vanderbilt-Ingram Cancer Center in Nashville, TN and the Boston Baskin Cancer Group in Memphis, TN. A total of 52 people consented to take part in this study and 15 were ineligible. One participant had disease progression before beginning treatment and wasn't assigned to a treatment arm.

Arm/Group Title	VRD (VELCADE, Lenalidomide, Dexamethasone)	VDD (VELCADE, Liposomal Doxorubicin, Dexamethasone)
Arm/Group Description	VELCADE, Lenalidomide, Dexamethasone VELCADE: 1.3 mg/m2 by IV on days 1, 4, 8, 11 of each cycle Lenalidomide: 25 mg by mouth on days 1-4 of each cycle Dexamethasone: 20 mg the day before and the day after receiving VELCADE DVT prophylaxis: At least one asprin 81 mg per day. Other option per physician's choice Bisphosphonates: Zoledronic acid by IB or pamidronate by IV can be used as per standard of care.	VELCADE, liposomal doxorubicin, dexamethasone VELCADE: 1.3 mg/m2 by IV on days 1, 4, 8, 11 of each cycle DVT prophylaxis: At least one asprin 81 mg per day. Other option per physician's choice Liposomal doxorubicin: 30 mg/m2 on day 4 of each cycle Dexamethasone: 40 mg by mouth on days 1-4, 8-11, and 15-18 of cycle 1 and days 1-4 on cycle 2-4
Period Title: Overall Study
STARTED	33	3
COMPLETED	23	3
NOT COMPLETED	10	0

Baseline Characteristics

Arm/Group Title	VRD (VELCADE, Lenalidomide, Dexamethasone)	VDD (VELCADE, Liposomal Doxorubicin, Dexamethasone)	Total
Arm/Group Description	VELCADE, Lenalidomide, Dexamethasone VELCADE: 1.3 mg/m2 by IV on days 1, 4, 8, 11 of each cycle Lenalidomide: 25 mg by mouth on days 1-4 of each cycle Dexamethasone: 20 mg the day before and the day after receiving VELCADE DVT prophylaxis: At least one asprin 81 mg per day. Other option per physician's choice Bisphosphonates: Zoledronic acid by IB or pamidronate by IV can be used as per standard of care.	VELCADE, liposomal doxorubicin, dexamethasone VELCADE: 1.3 mg/m2 by IV on days 1, 4, 8, 11 of each cycle DVT prophylaxis: At least one asprin 81 mg per day. Other option per physician's choice Liposomal doxorubicin: 30 mg/m2 on day 4 of each cycle Dexamethasone: 40 mg by mouth on days 1-4, 8-11, and 15-18 of cycle 1 and days 1-4 on cycle 2-4	Total of all reporting groups
Overall Participants	33	3	36
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	24 72.7%	3 100%	27 75%
>=65 years	9 27.3%	0 0%	9 25%
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	60 (8.71411)	48 (4.642796)	58.5 (8.803890)
Sex: Female, Male (Count of Participants)
Female	13 39.4%	0 0%	13 36.1%
Male	20 60.6%	3 100%	23 63.9%
Region of Enrollment (participants) [Number]
United States	33 100%	3 100%	36 100%

Outcome Measures

1. Primary Outcome

Title	The Percent of Patients With Minimal Residual Disease (MRD) Status Changing to Negative at Day 100 (Post-AHCT), Among Patients With MRD Positive at the End of Induction (EOI).
Description	Patients were treated with induction therapy (VRD) followed by autologous hematopoietic cell transplant (AHCT). MRD status of a patient with at least partial response was evaluated at the end of induction (EOI) and day 100 (post-AHCT). MRD of a patient is measured by seven-color flow cytometry.
Time Frame	6-months post ASCT

Outcome Measure Data

Analysis Population Description

Newly diagnosed, symptomatic multiple myeloma (MM) patients. Patients were treated with induction therapy VRD followed by AHCT. MRD staus was evaluated for patients with at least partial response at the end of induction (EOI) therapy. Ten of these patients had MRD negative at EOI.

Arm/Group Title	VELCADE, Lenalidomide, Dexamethasone (VRD)	VELCADE, Liposomal Doxorubicin, Dexamethasone (VDD)
Arm/Group Description	VELCADE, Lenalidomide, Dexamethasone VELCADE: 1.3 mg/m2 by IV on days 1, 4, 8, 11 of each cycle Lenalidomide: 25 mg by mouth on days 1-4 of each cycle Dexamethasone: 20 mg the day before and the day after receiving VELCADE DVT prophylaxis: At least one asprin 81 mg per day. Other option per physician's choice Bisphosphonates: Zoledronic acid by IB or pamidronate by IV can be used as per standard of care.	VELCADE, liposomal doxorubicin, dexamethasone VELCADE: 1.3 mg/m2 by IV on days 1, 4, 8, 11 of each cycle DVT prophylaxis: At least one asprin 81 mg per day. Other option per physician's choice Liposomal doxorubicin: 30 mg/m2 on day 4 of each cycle Dexamethasone: 40 mg by mouth on days 1-4, 8-11, and 15-18 of cycle 1 and days 1-4 on cycle 2-4
Measure Participants	20	0
Number (95% Confidence Interval) [percentage of participants]	30 90.9%

2. Secondary Outcome

Title	Progression Free Survival by MRD Status at Day 100.
Description	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time Frame	up to 7 years

Outcome Measure Data

Analysis Population Description

Patients with MRD status information at the EOI and day 100 (post-AHCT).

Arm/Group Title	MRD Negative at Day 100	MRD Status Positive at Day 100 (Post-AHCT)
Arm/Group Description	Patients with MRD status negative at day 100 (post-AHCT). They have MRD negative or positve at EOI.	Patients with MRD status stay positive at both EOI and day 100.
Measure Participants	13	7
Median (95% Confidence Interval) [years]	2.64	NA

Adverse Events

Arm/Group Title	VRD (VELCADE, Lenalidomide, Dexamethasone)		VDD (VELCADE, Liposomal Doxorubicin, Dexamethasone)
Arm/Group Description	VELCADE, Lenalidomide, Dexamethasone VELCADE: 1.3 mg/m2 by IV on days 1, 4, 8, 11 of each cycle Lenalidomide: 25 mg by mouth on days 1-4 of each cycle Dexamethasone: 20 mg the day before and the day after receiving VELCADE DVT prophylaxis: At least one asprin 81 mg per day. Other option per physician's choice Bisphosphonates: Zoledronic acid by IB or pamidronate by IV can be used as per standard of care.		VELCADE, liposomal doxorubicin, dexamethasone VELCADE: 1.3 mg/m2 by IV on days 1, 4, 8, 11 of each cycle DVT prophylaxis: At least one asprin 81 mg per day. Other option per physician's choice Liposomal doxorubicin: 30 mg/m2 on day 4 of each cycle Dexamethasone: 40 mg by mouth on days 1-4, 8-11, and 15-18 of cycle 1 and days 1-4 on cycle 2-4
All Cause Mortality
	VRD (VELCADE, Lenalidomide, Dexamethasone)		VDD (VELCADE, Liposomal Doxorubicin, Dexamethasone)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	VRD (VELCADE, Lenalidomide, Dexamethasone)		VDD (VELCADE, Liposomal Doxorubicin, Dexamethasone)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/33 (27.3%)		0/3 (0%)
Blood and lymphatic system disorders
Decreased hemoglobin	1/33 (3%)	1	0/3 (0%)	0
Anemia	1/33 (3%)	1	0/3 (0%)	0
Cardiac disorders
Ventricular arrhythmia	1/33 (3%)	1	0/3 (0%)	0
Gastrointestinal disorders
Gastritis	1/33 (3%)	1	0/3 (0%)	0
Gastric Schwannoma	1/33 (3%)	1	0/3 (0%)	0
Abdominal pain	2/33 (6.1%)	2	0/3 (0%)	0
GI bleed	1/33 (3%)	1	0/3 (0%)	0
Diarrhea	1/33 (3%)	1	0/3 (0%)	0
Nausea	1/33 (3%)	1	0/3 (0%)	0
General disorders
Fever	1/33 (3%)	1	0/3 (0%)	0
Infections and infestations
Infection with normal ANC - Esophagus	1/33 (3%)	1	0/3 (0%)	0
Urinary Tract Infection	1/33 (3%)	1	0/3 (0%)	0
Investigations
Elevated creatinine	1/33 (3%)	1	0/3 (0%)	0
Metabolism and nutrition disorders
dehydration	1/33 (3%)	1	0/3 (0%)	0
Potassium low	1/33 (3%)	1	0/3 (0%)	0
Musculoskeletal and connective tissue disorders
Hip fracture	1/33 (3%)	1	0/3 (0%)	0
Nervous system disorders
Sensory neuropathy	1/33 (3%)	1	0/3 (0%)	0
Respiratory, thoracic and mediastinal disorders
Shortness of breath	1/33 (3%)	1	0/3 (0%)	0
Acute respiratory failure	1/33 (3%)	1	0/3 (0%)	0
Pneumonia	1/33 (3%)	1	0/3 (0%)	0
Skin and subcutaneous tissue disorders
Rash, desquamation	1/33 (3%)	1	0/3 (0%)	0
Other (Not Including Serious) Adverse Events
	VRD (VELCADE, Lenalidomide, Dexamethasone)		VDD (VELCADE, Liposomal Doxorubicin, Dexamethasone)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/33 (93.9%)		3/3 (100%)
Blood and lymphatic system disorders
Febrile neutropenia	5/33 (15.2%)	5	0/3 (0%)	0
Hemoglobin	5/33 (15.2%)	8	1/3 (33.3%)	2
Platelets	4/33 (12.1%)	4	0/3 (0%)	0
Leukocytes	3/33 (9.1%)	6	0/3 (0%)	0
Blood/bone marrow - other	2/33 (6.1%)	4	0/3 (0%)	0
Lymphatics - other	3/33 (9.1%)	4	0/3 (0%)	0
Cardiac disorders
Cardiac (other)	2/33 (6.1%)	2	0/3 (0%)	0
Endocrine disorders
Low thyroid function	0/33 (0%)	0	1/3 (33.3%)	1
Eye disorders
Blurred vision	3/33 (9.1%)	3	0/3 (0%)	0
Gastrointestinal disorders
Nausea	14/33 (42.4%)	21	1/3 (33.3%)	2
Constipation	12/33 (36.4%)	15	2/3 (66.7%)	2
Diarrhea	9/33 (27.3%)	12	0/3 (0%)	0
Mucositis/stomatitis	7/33 (21.2%)	7	3/3 (100%)	3
Anorexia	5/33 (15.2%)	6	0/3 (0%)	0
Gastritis	3/33 (9.1%)	4	0/3 (0%)	0
Heartburn	2/33 (6.1%)	5	0/3 (0%)	0
Taste alteration	2/33 (6.1%)	2	0/3 (0%)	0
Gastrointestinal (other)	7/33 (21.2%)	9	0/3 (0%)	0
General disorders
Vomiting	5/33 (15.2%)	6	0/3 (0%)	0
Fatigue	15/33 (45.5%)	21	3/3 (100%)	5
Fever	8/33 (24.2%)	8	1/3 (33.3%)	1
Pain (other)	10/33 (30.3%)	12	0/3 (0%)	0
Gait disturbance	3/33 (9.1%)	3	0/3 (0%)	0
Swelling of limb	7/33 (21.2%)	10	0/3 (0%)	0
Flu-like syndrome	3/33 (9.1%)	3	0/3 (0%)	0
Immune system disorders
Allergic reaction	0/33 (0%)	0	2/3 (66.7%)	2
Autoimmune reaction	0/33 (0%)	0	1/3 (33.3%)	1
Infections and infestations
Infection, other	2/33 (6.1%)	2	0/3 (0%)	0
Infection with normal ANC - skin (cellulitis)	2/33 (6.1%)	2	0/3 (0%)	0
Infection with normal ANC - Upper airway NOS	2/33 (6.1%)	2	0/3 (0%)	0
Infection with normal ANC - Eye NOS	2/33 (6.1%)	2	0/3 (0%)	0
Infection with normal ANC - Abdomen NOS	0/33 (0%)	0	1/3 (33.3%)	1
Investigations
Weight gain	2/33 (6.1%)	2	0/3 (0%)	0
Weight loss	2/33 (6.1%)	7	0/3 (0%)	0
Metabolic/Laboratory (other)	4/33 (12.1%)	5	1/3 (33.3%)	5
Neutrophils/granulocytes	6/33 (18.2%)	10	1/3 (33.3%)	2
Metabolism and nutrition disorders
Potassium, serum-low	5/33 (15.2%)	5	0/3 (0%)	0
Glucose high	2/33 (6.1%)	2	2/3 (66.7%)	6
Calcium low	3/33 (9.1%)	3	0/3 (0%)	0
Alkaline phosphatase	2/33 (6.1%)	3	0/3 (0%)	0
Musculoskeletal and connective tissue disorders
Bone pain	4/33 (12.1%)	4	1/3 (33.3%)	1
Back pain	3/33 (9.1%)	3	0/3 (0%)	0
Muscle pain	3/33 (9.1%)	3	0/3 (0%)	0
Joint pain	2/33 (6.1%)	2	0/3 (0%)	0
Muscle/soft tissue, other	8/33 (24.2%)	18	0/3 (0%)	0
Muscle weakness	0/33 (0%)	0	1/3 (33.3%)	2
Nervous system disorders
Neuropathy: sensory	16/33 (48.5%)	31	2/3 (66.7%)	4
Dizziness	5/33 (15.2%)	8	0/3 (0%)	0
Neuropathy (motor)	3/33 (9.1%)	4	0/3 (0%)	0
Neurological (other)	5/33 (15.2%)	6	0/3 (0%)	0
Headache	5/33 (15.2%)	9	1/3 (33.3%)	6
neuralgia/peripheral nerve	2/33 (6.1%)	3	0/3 (0%)	0
Psychiatric disorders
Insomnia	3/33 (9.1%)	3	1/3 (33.3%)	2
Depression	3/33 (9.1%)	4	0/3 (0%)	0
Anxiety	0/33 (0%)	0	2/3 (66.7%)	2
Renal and urinary disorders
Renal (other)	2/33 (6.1%)	2	0/3 (0%)	0
Urinary frequency	2/33 (6.1%)	2	0/3 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pain-chest wall	2/33 (6.1%)	4	1/3 (33.3%)	1
Throat pain	2/33 (6.1%)	3	0/3 (0%)	0
Shortness of breath	9/33 (27.3%)	16	0/3 (0%)	0
Cough	4/33 (12.1%)	4	1/3 (33.3%)	1
Upper Respiratory - other	2/33 (6.1%)	2	1/3 (33.3%)	1
Sinus reactions	0/33 (0%)	0	1/3 (33.3%)	1
Voice change	0/33 (0%)	0	1/3 (33.3%)	1
Skin and subcutaneous tissue disorders
Rash/desquamation	7/33 (21.2%)	11	1/3 (33.3%)	3
Skin, other	5/33 (15.2%)	9	0/3 (0%)	0
Itching	0/33 (0%)	0	1/3 (33.3%)	1
Rash, erythema multiforme	2/33 (6.1%)	2	0/3 (0%)	0
Rash on hand-foot	0/33 (0%)	0	1/3 (33.3%)	1
Vascular disorders
Hypetension	4/33 (12.1%)	7	1/3 (33.3%)	1
Hypotension	2/33 (6.1%)	2	0/3 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT 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.