Phase II Trial of Revlimid® and Rituximab for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

• Sponsor: University of California, San Diego (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01199575
• Collaborator: Celgene Corporation (Industry)
• Enrollment: 30
• Location: 1
• Arm: 1
• Duration (Months): 172
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) is conducting a two-arm, multi-center phase II trial of Revlimid® and rituximab for Relapsed or Refractory CLL for patients under the age of 65 and patients 65 years and older.

Lenalidomide (Revlimid) is an immunomodulatory agent with promising clinical activity in CLL and is FDA approved for treatment of relapsed multiple myeloma and 5q-myelodysplastic syndrome. Rituximab (Rituxan) is a monoclonal antibody to CD20 that is approved for the treatment of CLL.

The primary objective of this study is to determine the overall response rate of the combination of Revlimid® and rituximab in previously treated CLL patients. All patients will receive treatment with Revlimid® starting at a low dose that will be dose escalated based on individual patient tolerability. The combination of Revlimid and Rituximab will be administered for a maximum of 7 cycles. Patients with residual leukemia following seven cycles of treatment with the combination may elect to continue on protocol for an additional 6 cycles of single agent Revlimid® consolidation.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia; CLL	Drug: Revlimid; Drug: Rituximab	Phase 2

Detailed Description

The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) is conducting a two-arm, multicenter phase II trial of Revlimid® and rituximab for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) for patients under the age of 65 and patients 65 years and older.

Revlimid® (lenalidomide) a derivative of thalidomide with immune-modulating properties. Revlimid® is FDA approved for treatment of relapsed multiple myeloma and 5q- myelodysplastic syndrome. Revlimid® has promising clinical activity, in both previously treated and treatment naive CLL in early clinical trials. However, the mechanism(s) whereby Revlimid® is active in CLL is unknown. Rituximab (Rituxan®) is a monoclonal antibody that binds to CD20 expressed on normal and leukemia B cells. Rituximab is approved for the treatment of CLL.

In preclinical models of lymphoma Revlimid improved the activity of Rituximab. In clinical studies of relapsed and/or refractory CLL the combination Revlimid and Rituximab was associated with better therapeutic effects compared with what was historically observed with either agent alone.

The purpose of this study is to evaluate the safety and activity of the combination of Revlimid® and rituximab in relapsed or refractory CLL, elucidate the mechanism of action of Revlimid® in CLL, and to assess whether prognostic factors might predict those patients likely to benefit from this therapy in the future.

The primary objective of this study is to determine the overall response rate (ORR) of the combination of Revlimid® and rituximab in previously treated CLL patients for those age 65 years and above and those younger than 65.

Secondary objectives will evaluate the safety of the combination of Revlimid® and Rituximab, response duration, improvement in hematologic parameters, activity of the combination in high-risk CLL subsets, the significance of the tumor flare reaction and to compare the activity of this regimen when administered to previously treated patients to our protocol in the front line setting and to compare these outcomes for both arms of the study.

All patients will receive treatment with Revlimid® starting at a low dose that will be slowly dose escalated based on individual patient tolerability. The combination of Revlimid and Rituximab will be administered for a maximum of 7 cycles. Patients with residual leukemia following seven cycles of treatment with the combination may elect to continue on protocol for an additional 6 cycles of single agent Revlimid® consolidation.

All patients will have baseline assessment of known CLL prognostic factors through the CRC tissue core. These known prognostic features in CLL together with novel prognostic factors will be evaluated for the ability to predict response to treatment with Revlimid® and the combination of Revlimid® and Rituximab.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Revlimid® and Rituximab, for the Treatment of Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Jan 1, 2015
• Anticipated Study Completion Date: Dec 1, 2024

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Revlimid + Rituximab A: Lenalidomide starting at a low dose 2.5 or 5 mg, 21 days/cycle escalated based on patient tolerability. Rituximab at 375mg/m2 administered following the first 21 days of lenalidomide monotherapy, continued weekly throughout cycle 2, and then every 4 weeks for subsequent cycles (3-7). Each patient may receive up to 7 cycles of treatment with the combination lenalidomide/rituximab if no progressive disease or significant toxicity. Patients with residual disease can elect to receive 6 additional cycles of single agent Revlimid as consolidation. Each patient may receive up to a maximum of 13 cycles of treatment if no progressive disease or significant toxicity.

Drug: Revlimid; Other Names: lenalidomide ; Drug: Rituximab; Other Names: Rituxan

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) [nine months]

Secondary Outcome Measures

1. Adverse Events to Study Treatment [one year]

2. Progression Free Survival. [2 years]

3. Conversion of MRD-positive Complete Response or Partial Response (PR) to a MRD-negative Complete Response (CR) or Complete Response (CR) Respectively Following an Additional 6 Cycles of Revlimid Consolidation [13 cycles]

4. Overall Survival [4 years]

5. Treatment Free Survival. [2 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Diagnosis of chronic lymphocytic leukemia (CLL).

2. Subjects must have active disease appropriate for therapy.

3. Previous treatment for CLL

4. Understand and voluntarily sign an informed consent form.

5. Age ≥18 years at the time of signing the informed consent form.

6. Able to adhere to the study visit schedule and other protocol requirements.

7. ECOG performance status of ≤ 2 at study entry (see Appendix B).

8. Laboratory test results within these ranges: Absolute neutrophil count ≥ 1.0 x 109/L,Platelet count ≥ 50 x 109/L, Total bilirubin ≤ 1.5 mg/dL, AST (SGOT) and ALT (SGPT) ≤ 2 x ULN, Creatinine clearance estimated to be ≥ 30 ml/min

9. Disease free of prior malignancies for ≥ 2 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ" of the cervix or breast.

10. Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting Revlimid® and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking Revlimid®. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. See Appendix: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods, AND also Appendix: Education and Counseling Guidance Document.

Exclusion Criteria:

1. Known Hepatitis B Ag positive, Hepatitis C positive patients.

2. Known HIV positive patients.

3. Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune thrombocytopenia (ITP).

4. Inability to provide informed consent.

5. Concurrent malignancy (excluding basal and squamous cell skin cancers).

6. Active fungal, bacterial, and/or viral infection.

7. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.

8. Pregnant or breast-feeding females. (Lactating females must agree not to breast feed while taking Revlimid®).

9. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.

10. Use of any other experimental drug or therapy within 28 days of baseline.

11. Known hypersensitivity to thalidomide.

12. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.

13. Concurrent use of other anti-cancer agents or treatments.

14. Patients with history of deep venous thrombus or pulmonary embolism. Patients who are at increased risk of thrombosis during treatment with Revlimid® including those taking concurrent erythropoietin, darbepoetin or high-dose corticosteroids are also excluded.

15. Patients with a history of embolic events (e.g. TIA) from arrhythmia or peripheral arterial disease or of recent mycocardial infarction whether or not treated with anti-platelet drugs.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Diego	La Jolla	California	United States	92093

Sponsors and Collaborators

• University of California, San Diego
• Celgene Corporation

Investigators

• Study Director: Thomas J Kipps, MD, PhD, Director of the CLL Research Consortium and University of California San Diego

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Website for the CLL Research Consortium
• Moore's UCSD Cancer Center

Publications

None provided.

• Responsible Party: Thomas Kipps, Professor, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT01199575
• Other Study ID Numbers: CRC022
• First Posted: Sep 13, 2010
• Last Update Posted: Sep 29, 2021
• Last Verified: Sep 1, 2021

• Keywords provided by Thomas Kipps, Professor, University of California, San Diego: Chronic Lymphocytic Leukemia; CLL; Relapsed or Refractory; previously treated
• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Rituximab; Lenalidomide

Study Results

Participant Flow

Arm/Group Title	Revlimid + Rituximab
Arm/Group Description	Lenalidomide starting at a low dose 2.5 or 5 mg, 21 days/cycle escalated based on patient tolerability. Rituximab at 375mg/m2 administered following the first 21 days of lenalidomide monotherapy, continued weekly throughout cycle 2, and then every 4 weeks for subsequent cycles (3-7). Each patient may receive up to 7 cycles of treatment with the combination lenalidomide/rituximab if no progressive disease or significant toxicity. Patients with residual disease can elect to receive 6 additional cycles of single agent Revlimid as consolidation. Each patient may receive up to a maximum of 13 cycles of treatment if no progressive disease or significant toxicity.
Period Title: Overall Study
STARTED	30
COMPLETED	25
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Revlimid + Rituximab
Arm/Group Description	Lenalidomide starting at a low dose 2.5 or 5 mg, 21 days/cycle escalated based on patient tolerability. Rituximab at 375mg/m2 administered following the first 21 days of lenalidomide monotherapy, continued weekly throughout cycle 2, and then every 4 weeks for subsequent cycles (3-7). Each patient may receive up to 7 cycles of treatment with the combination lenalidomide/rituximab if no progressive disease or significant toxicity. Patients with residual disease can elect to receive 6 additional cycles of single agent Revlimid as consolidation. Each patient may receive up to a maximum of 13 cycles of treatment if no progressive disease or significant toxicity.
Overall Participants	30
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	11 36.7%
>=65 years	19 63.3%
Sex: Female, Male (Count of Participants)
Female	11 36.7%
Male	19 63.3%
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	0 0%
White	30 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	30 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR)
Time Frame	nine months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Revlimid + Rituximab
Arm/Group Description	A: Lenalidomide starting at a low dose 2.5 or 5 mg, 21 days/cycle escalated based on patient tolerability. Rituximab at 375mg/m2 administered following the first 21 days of lenalidomide monotherapy, continued weekly throughout cycle 2, and then every 4 weeks for subsequent cycles (3-7). Each patient may receive up to 7 cycles of treatment with the combination lenalidomide/rituximab if no progressive disease or significant toxicity. Patients with residual disease can elect to receive 6 additional cycles of single agent Revlimid as consolidation. Each patient may receive up to a maximum of 13 cycles of treatment if no progressive disease or significant toxicity. Revlimid Rituximab
Measure Participants	25
Count of Participants [Participants]	25 83.3%

2. Secondary Outcome

Title	Adverse Events to Study Treatment
Time Frame	one year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Revlimid + Rituximab
Arm/Group Description	Lenalidomide starting at a low dose 2.5 or 5 mg, 21 days/cycle escalated based on patient tolerability. Rituximab at 375mg/m2 administered following the first 21 days of lenalidomide monotherapy, continued weekly throughout cycle 2, and then every 4 weeks for subsequent cycles (3-7). Each patient may receive up to 7 cycles of treatment with the combination lenalidomide/rituximab if no progressive disease or significant toxicity. Patients with residual disease can elect to receive 6 additional cycles of single agent Revlimid as consolidation. Each patient may receive up to a maximum of 13 cycles of treatment if no progressive disease or significant toxicity.
Measure Participants	25
Count of Participants [Participants]	25 83.3%

3. Secondary Outcome

Title	Progression Free Survival.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Conversion of MRD-positive Complete Response or Partial Response (PR) to a MRD-negative Complete Response (CR) or Complete Response (CR) Respectively Following an Additional 6 Cycles of Revlimid Consolidation
Time Frame	13 cycles

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Overall Survival
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Treatment Free Survival.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Revlimid + Rituximab
Arm/Group Description	Lenalidomide starting at a low dose 2.5 or 5 mg, 21 days/cycle escalated based on patient tolerability. Rituximab at 375mg/m2 administered following the first 21 days of lenalidomide monotherapy, continued weekly throughout cycle 2, and then every 4 weeks for subsequent cycles (3-7). Each patient may receive up to 7 cycles of treatment with the combination lenalidomide/rituximab if no progressive disease or significant toxicity. Patients with residual disease can elect to receive 6 additional cycles of single agent Revlimid as consolidation. Each patient may receive up to a maximum of 13 cycles of treatment if no progressive disease or significant toxicity.
All Cause Mortality
	Revlimid + Rituximab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Revlimid + Rituximab
	Affected / at Risk (%)	# Events
Total	11/25 (44%)
Blood and lymphatic system disorders
neutropenia	7/25 (28%)	9
hypophosphatemia	1/25 (4%)	1
Thrombocytopenia	1/25 (4%)	1
Injury, poisoning and procedural complications
Bullous arthropod reaction	1/25 (4%)	1
Vascular disorders
Deep Vein Thrombosis	1/25 (4%)	1
Other (Not Including Serious) Adverse Events
	Revlimid + Rituximab
	Affected / at Risk (%)	# Events
Total	25/25 (100%)
Blood and lymphatic system disorders
acidosis	5/25 (20%)	5
anemia	16/25 (64%)	26
bicarbonate decrease	1/25 (4%)	1
blood biliruben increase	5/25 (20%)	6
hematoma	1/25 (4%)	1
hematoma - retroperritoneal	1/25 (4%)	1
hemolysis	1/25 (4%)	1
high cholesterol	1/25 (4%)	1
hypercalcemia	2/25 (8%)	5
hyperkalemia	7/25 (28%)	7
hypermagnesemia	1/25 (4%)	1
hypernatremia	1/25 (4%)	2
hyperphosphatemia	12/25 (48%)	19
hyperuricemia	7/25 (28%)	15
hypoalbuminemia	8/25 (32%)	9
hypocalcemia	20/25 (80%)	30
hypokalemia	3/25 (12%)	6
hypomagnesemia	1/25 (4%)	1
hyponatremia	15/25 (60%)	25
hypophosphatemia	15/25 (60%)	23
leukopenia	1/25 (4%)	2
low uric acid	1/25 (4%)	1
neutropenia	22/25 (88%)	42
thrombocytopenia	20/25 (80%)	28
Cardiac disorders
atrial fibrillation	2/25 (8%)	2
bradycardia	6/25 (24%)	8
palpitations	2/25 (8%)	2
sinus arrhythmia	1/25 (4%)	1
tachycardia	3/25 (12%)	3
ventricular arrhythmia	1/25 (4%)	1
Ear and labyrinth disorders
tinnitus	1/25 (4%)	1
Endocrine disorders
elevated TSH	1/25 (4%)	1
hypothyroidism	1/25 (4%)	2
Eye disorders
blurred vision	1/25 (4%)	1
conjunctivitis	1/25 (4%)	1
retinal detachment	1/25 (4%)	1
right eye floater	1/25 (4%)	1
watering eyes	1/25 (4%)	1
Gastrointestinal disorders
abdominal distension	5/25 (20%)	6
acid reflux	1/25 (4%)	1
constipation	14/25 (56%)	20
diarrhea	14/25 (56%)	27
diverticulitis	1/25 (4%)	1
dyspepsia	7/25 (28%)	7
flatulance	4/25 (16%)	6
gastroenteritis	1/25 (4%)	2
GERD	1/25 (4%)	1
GI Problems	1/25 (4%)	1
nausea	16/25 (64%)	23
small intestine infection	1/25 (4%)	1
vomiting	8/25 (32%)	9
General disorders
alopecia	1/25 (4%)	1
bruising	4/25 (16%)	5
chills/rigors	15/25 (60%)	21
cough	18/25 (72%)	23
dehydration	6/25 (24%)	7
dry mouth	4/25 (16%)	4
dysphagia	2/25 (8%)	2
ecchymosis	4/25 (16%)	4
edema	13/25 (52%)	14
edema - eyelid	1/25 (4%)	1
edema - facial	1/25 (4%)	1
elevated LDH	5/25 (20%)	6
epistaxis	4/25 (16%)	4
fatigue	19/25 (76%)	28
fever	14/25 (56%)	18
flu-like symptoms	13/25 (52%)	19
flushing	1/25 (4%)	1
headache	8/25 (32%)	13
hemorrhage - oral	3/25 (12%)	3
hemorrhage - rectal	1/25 (4%)	3
hoarseness	1/25 (4%)	1
hot flashes	3/25 (12%)	6
hyperhidrosis	14/25 (56%)	17
insomnia	14/25 (56%)	23
libido decrease	1/25 (4%)	1
night sweats	14/25 (56%)	20
pain - abdominal	10/25 (40%)	14
pain - back	11/25 (44%)	18
pain - chest	4/25 (16%)	5
pain - chest - non-cardiac	1/25 (4%)	1
pain - ear	2/25 (8%)	2
pain - extremity	14/25 (56%)	19
pain - eye	1/25 (4%)	1
pain - facial	1/25 (4%)	2
pain - hip	4/25 (16%)	6
pain - knee	1/25 (4%)	1
pain - lymph node	3/25 (12%)	3
pain - neck	2/25 (8%)	3
pain - pharyngolaryngeal	12/25 (48%)	14
pain - rectal	1/25 (4%)	1
pain - ribs	1/25 (4%)	2
pain - right disessciata	1/25 (4%)	1
pain - right side	1/25 (4%)	1
pain - stomach	9/25 (36%)	12
pain - tumor	12/25 (48%)	16
restless leg syndrome	1/25 (4%)	1
rhinitis	2/25 (8%)	2
swelling - tongue	1/25 (4%)	1
syncope	2/25 (8%)	2
Hepatobiliary disorders
alkaline phosphatase increase	7/25 (28%)	7
elevated ALT	12/25 (48%)	15
elevated AST	15/25 (60%)	16
Immune system disorders
allergic reaction	1/25 (4%)	1
rhinitis - allergic rhinitis	11/25 (44%)	16
Infections and infestations
bladder infection	1/25 (4%)	1
febrile illness	1/25 (4%)	1
laryngitis	1/25 (4%)	1
sinusitis	5/25 (20%)	8
Upper Respiratory Infection	13/25 (52%)	16
Injury, poisoning and procedural complications
fracture	1/25 (4%)	1
hemorrhage - cut	1/25 (4%)	1
infusion reaction - cytokine release syndrome	2/25 (8%)	2
palmar-plantar erythrodysesthia	1/25 (4%)	1
tumor flare reaction	3/25 (12%)	5
Metabolism and nutrition disorders
anorexia	11/25 (44%)	14
early satiety	3/25 (12%)	3
weight gain	1/25 (4%)	1
weight loss	15/25 (60%)	18
Musculoskeletal and connective tissue disorders
arthralgia	5/25 (20%)	8
arthritis	2/25 (8%)	2
arthritis (gout big toe)	1/25 (4%)	1
body aches	2/25 (8%)	4
bursitis	1/25 (4%)	1
gait disturbance	2/25 (8%)	2
general muscle weakness	12/25 (48%)	18
lumbar disc disease	1/25 (4%)	1
myalgia	14/25 (56%)	22
osteopenia	2/25 (8%)	2
pain - abdominal/stomach - cramps	1/25 (4%)	3
tendonitis	2/25 (8%)	2
Nervous system disorders
cognitive disturbance	1/25 (4%)	1
cognitive impairment	1/25 (4%)	1
confusion	2/25 (8%)	2
dizziness	11/25 (44%)	15
dysesthia	1/25 (4%)	1
dysgeusia	1/25 (4%)	1
memory impairment	3/25 (12%)	3
neuropathy	10/25 (40%)	13
neuropathy - leg and finger spasms	1/25 (4%)	1
pain - skin	1/25 (4%)	1
sciatica	1/25 (4%)	1
taste alteration	1/25 (4%)	1
tremors	3/25 (12%)	3
Psychiatric disorders
depression	1/25 (4%)	1
psychosis	1/25 (4%)	1
Renal and urinary disorders
acute renal failure	1/25 (4%)	1
bladder spasm	1/25 (4%)	1
dysuria	2/25 (8%)	2
elevated creatinine	10/25 (40%)	15
fluid retention	1/25 (4%)	1
hydronephrosis	1/25 (4%)	1
proteinuria	1/25 (4%)	1
urinary frequency	10/25 (40%)	12
urinary retention	2/25 (8%)	2
urinary tract infection	2/25 (8%)	2
urine discoloration	2/25 (8%)	2
urine odor	1/25 (4%)	1
Reproductive system and breast disorders
prostatitis	2/25 (8%)	2
vaginal odor	1/25 (4%)	1
yeast (vaginal) infection	1/25 (4%)	3
Respiratory, thoracic and mediastinal disorders
bronchitis	4/25 (16%)	4
bronchospasm/wheezing	2/25 (8%)	2
dyspnea	7/25 (28%)	7
shortness of breath	1/25 (4%)	1
Skin and subcutaneous tissue disorders
canker sore	3/25 (12%)	5
cyst	1/25 (4%)	1
dry skin	4/25 (16%)	4
keratosis	1/25 (4%)	1
keratosis - actinic keratosis	1/25 (4%)	2
lesion	5/25 (20%)	5
pruritis	10/25 (40%)	16
rash	15/25 (60%)	24
skin and subcutaneous tissue disorder	1/25 (4%)	1
skin hyperpigmentation	5/25 (20%)	5
skin infection	2/25 (8%)	2
skin infection - cellulitis	1/25 (4%)	1
skin ulceration	3/25 (12%)	4
skin ulceration - blister on roof of mouth	1/25 (4%)	1
skin ulceration - finger	1/25 (4%)	1
ulcer - mouth	1/25 (4%)	1
urticaria	1/25 (4%)	1
Social circumstances
anxiety	15/25 (60%)	29
distress	5/25 (20%)	5
Vascular disorders
hypertension	4/25 (16%)	4
hypotension	8/25 (32%)	10
purpura	1/25 (4%)	1
superficial phlebitis	1/25 (4%)	1
thrombophlebitis	1/25 (4%)	1
thrombophlebitis - superficial	4/25 (16%)	7

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.