Interferon and GM-CSF Compared With Imatinib Mesylate and Vaccine Therapy in Patients With Chronic Phase CML on a TKI

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT00363649
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 36
• Location: 1
• Arms: 2
• Actual Duration (Months): 132
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Tyrosine kinase inhibitors may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Interferon alfa may interfere with the growth of cancer cells. GM-CSF may help cells that are involved in the body's immune response work better. Vaccines made from a person's cancer cells may help the body build an effective immune response to kill cancer cells.

PURPOSE: This randomized phase II trial is studying tyrosine kinase inhibitors, interferon alfa, and GM-CSF to see how well they work compared to tyrosine kinase inhibitors and vaccine therapy in treating patients with chronic phase chronic myelogenous leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Biological: GM-K562 cell vaccine; Biological: Interferon alfa; Biological: Sargramostim	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Compare clinical response, in terms of 1-year progression-free survival and rate of molecular complete remission, in patients with Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML) in chronic phase who have achieved a complete cytogenetic remission to single-agent tyrosine kinase inhibitor treated with interferon alfa and sargramostim (GM-CSF) vs tyrosine kinase inhibitor and GM-K562 cell vaccine.

Secondary

• Compare time to Ph-negativity by polymerase chain reaction after randomization.

• Compare disease-free survival and percent molecular complete remissions.

• Determine the toxicity of these treatment regimens in these patients.

OUTLINE: This is a multicenter, randomized, crossover, study. Patients are randomized to 1 of 2 treatment arms. The study will be modified based on the results of the planned interim analysis. Individual Study Arms will continue to accrue and treat as indicated by the analysis. The study in its current format will continue should the planned interim analysis indicate both Study Arms remain viable as effective treatments.

All patients continue to receive their standard dose of tyrosine kinase inhibitor in addition to 1 of the following treatment arms:

• Arm I : Patients receive interferon alfa subcutaneously (SC) and GM-CSF SC once daily for 6 months. Patients who achieve a molecular complete remission (CR) (defined as BCR-ABL-negative disease confirmed by 2 PCR assays separated by 1 month) at the end of the 6-month period, discontinue study therapy and are monitored for disease recurrence by blood tests every 4 weeks. Patients who do not achieve a molecular CR (defined as BCR-ABL-positive disease) after completion of the initial 6 months of therapy, receive an additional 6 months of therapy as above. Patients who achieve BCR-ABL-negative disease during the additional 6 months of therapy, discontinue study therapy and are monitored for disease recurrence by blood tests every 4 weeks. Patients who remain BCR-ABL-positive by PCR after an additional 6 months of therapy, are eligible to cross over to arm II.

If at any time after stopping study therapy blood tests show disease recurrence, patients restart tyrosine kinase inhibitor and are eligible to cross over to arm II. Patients are also eligible to cross over to arm II in the presence of unacceptable toxicity.

• Arm II: Patients receive GM-K562 cell vaccine intradermally once every 3 weeks for a minimum of 6 months. Patients with BCR-ABL-negative disease at the end of the 6-month period discontinue study therapy and are monitored for disease recurrence by blood tests every 4 weeks. Patients with BCR-ABL-positive disease after the completion of the initial 6 months of therapy, receive an additional 6 months of therapy as above. Patients who achieve BCR-ABL-negative disease during the additional 6 months of therapy, discontinue study therapy and are monitored every 4 weeks for disease recurrence. Patients who remain BCR-ABL-positive after the additional 6 months of therapy, are eligible to cross over to arm I.

If at any time after stopping study therapy blood tests show disease recurrence, patients restart tyrosine kinase inhibitor and are eligible to cross over to arm I. Patients are also eligible to cross over to arm I in the presence of unacceptable toxicity.

After completion of study therapy, patients are followed periodically for up to 1 year.

As of May 2014, Study Arm B is not available to newly accrued and enrolled subjects based on the interim analysis directing all new subjects to the combination of Interferon + GM-CSF.

PROJECTED ACCRUAL: A total of 56 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Participants were randomly assigned to Arm A or Arm B and received up to twelve months of protocol therapy. If at any point a participant progressed, relapsed, or had unacceptable toxicity, they could cross over to the other arm. Participants could only cross over once.Participants were randomly assigned to Arm A or Arm B and received up to twelve months of protocol therapy. If at any point a participant progressed, relapsed, or had unacceptable toxicity, they could cross over to the other arm. Participants could only cross over once.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Trial of Interferon + GM-CSF Versus K562/GM-CSF Vaccination in CML Patients Achieving a Complete Cytogenetic Response to Frontline Tyrosine Kinase Inhibitor Therapy
• Actual Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Sep 1, 2017
• Actual Study Completion Date: Sep 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A Patients will receive injections of interferon alfa and sargramostim once a day for 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm II.	Biological: Interferon alfa; Given by injection; Biological: Sargramostim; Given by injection; Other Names: GM-CSF
Experimental: Arm B Patients will receive an injection of GM-K562 cell vaccine every 3 weeks for at least 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm I. NOTE: Study Arm B is not available to newly accrued and enrolled subjects based on the interim analysis directing all new subjects to the combination of Interferon + sargramostim (Arm A).	Biological: GM-K562 cell vaccine; Given by injection

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [1 year after treatment has been stopped]

   Number of patients alive and without disease progression or relapse

2. Complete Remission Rate [Up to 18 months]

   Percentage of patients who achieved molecular remission as defined by polymerase chain reaction negativity.

Secondary Outcome Measures

1. Time to Complete Molecular Remission [Up to 27 months]

   Number of months from randomization to molecular remission as defined by polymerase chain reaction negativity.

2. Disease-free Survival [Up to 8 years]

   Median number of days to progression of disease in participants who stopped all treatment as directed by the protocol.

3. Early Discontinuation [1 year]

   Number of participants unable to complete protocol-specified treatment due to toxicity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Diagnosis of chronic myelogenous leukemia (CML) in chronic phase based on cytogenetic detection of the Philadelphia chromosome and/or detection of the BCR-ABL rearrangement by any of the following molecular methods:

• Recombinant DNA analysis of the BCR-ABL fusion gene

• Fluorescence in situ hybridization (FISH)

• Polymerase chain reaction detection of the BCR-ABL hybrid mRNA

• Documentation of complete cytogenetic response by conventional cytogenetic or FISH analysis while on a stable dose of tyrosine kinase inhibitor

• No other phase of CML

PATIENT CHARACTERISTICS:

• ECG performance status 0-2

• Life expectancy > 24 months

• Not pregnant

• Negative pregnancy test

• Fertile patients must use effective contraception

• Creatinine ≤ 2.0 mg/dL

• Bilirubin ≤ 2.0 times upper limit of normal (ULN)

• AST and ALT ≤ 2.5 times ULN

• No other malignancy within the past 5 years except in situ cervical carcinoma or adequately treated nonmelanoma skin cancer

• No other disease requiring long-term corticosteroids or immunosuppressants

PRIOR CONCURRENT THERAPY:

• At least 28 days since prior investigational agents

• No prior bone marrow transplant or other transplant

• No concurrent immunosuppressants (e.g., steroids, cyclosporine, azathioprine, mycophenolate mofetil, sirolimus, or tacrolimus)

• No concurrent hydroxyurea, busulfan, or cytoreductive agents (other than frontline TKI)

• No other concurrent anticancer agents or therapies

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: B. Douglas Smith, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 25, 2014

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT00363649
• Other Study ID Numbers: J05121; P30CA006973
• First Posted: Aug 15, 2006
• Last Update Posted: Nov 13, 2018
• Last Verified: Oct 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia
• Additional relevant MeSH terms: Leukemia; Interferons; Interferon-alpha; Sargramostim

Study Results

Participant Flow

Pre-assignment Detail	Two participants were screen failures.

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Patients will receive injections of interferon alfa and sargramostim once a day for 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm II. Interferon alfa: Given by injection Sargramostim: Given by injection	Patients will receive an injection of GM-K562 cell vaccine every 3 weeks for at least 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm I. NOTE: Study Arm B is not available to newly accrued and enrolled subjects based on the interim analysis directing all new subjects to the combination of Interferon + sargramostim (Arm A). GM-K562 cell vaccine: Given by injection
Period Title: Overall Study
STARTED	18	16
Crossed Over to Arm B	9	0
Crossed Over to Arm A	0	12
Did Not Cross Over	2	3
COMPLETED	11	15
NOT COMPLETED	7	1

Baseline Characteristics

Arm/Group Title	Arm A	Arm B	Total
Arm/Group Description	Patients will receive injections of interferon alfa and sargramostim once a day for 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm II. Interferon alfa: Given by injection Sargramostim: Given by injection	Patients will receive an injection of GM-K562 cell vaccine every 3 weeks for at least 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm I. NOTE: Study Arm B is not available to newly accrued and enrolled subjects based on the interim analysis directing all new subjects to the combination of Interferon + sargramostim (Arm A). GM-K562 cell vaccine: Given by injection	Total of all reporting groups
Overall Participants	18	16	34
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	18 100%	16 100%	34 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	43	40	40.5
Sex: Female, Male (Count of Participants)
Female	10 55.6%	10 62.5%	20 58.8%
Male	8 44.4%	6 37.5%	14 41.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	17 94.4%	15 93.8%	32 94.1%
Unknown or Not Reported	1 5.6%	1 6.3%	2 5.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 11.1%	1 6.3%	3 8.8%
White	15 83.3%	14 87.5%	29 85.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 5.6%	1 6.3%	2 5.9%
Region of Enrollment (Count of Participants)
United States	18 100%	16 100%	34 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	Number of patients alive and without disease progression or relapse
Time Frame	1 year after treatment has been stopped

Outcome Measure Data

Analysis Population Description

Crossover participants were not analyzed for this outcome. This is as per the analysis plan written in this protocol.

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Patients will receive injections of interferon alfa and sargramostim once a day for 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm II. Interferon alfa: Given by injection Sargramostim: Given by injection	Patients will receive an injection of GM-K562 cell vaccine every 3 weeks for at least 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm I. NOTE: Study Arm B is not available to newly accrued and enrolled subjects based on the interim analysis directing all new subjects to the combination of Interferon + sargramostim (Arm A). GM-K562 cell vaccine: Given by injection
Measure Participants	18	16
Count of Participants [Participants]	2 11.1%	0 0%

2. Primary Outcome

Title	Complete Remission Rate
Description	Percentage of patients who achieved molecular remission as defined by polymerase chain reaction negativity.
Time Frame	Up to 18 months

Outcome Measure Data

Analysis Population Description

Crossover participants were not analyzed for this outcome. This is as per the analysis plan written in this protocol.

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Patients will receive injections of interferon alfa and sargramostim once a day for 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm II. Interferon alfa: Given by injection Sargramostim: Given by injection	Patients will receive an injection of GM-K562 cell vaccine every 3 weeks for at least 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm I. NOTE: Study Arm B is not available to newly accrued and enrolled subjects based on the interim analysis directing all new subjects to the combination of Interferon + sargramostim (Arm A). GM-K562 cell vaccine: Given by injection
Measure Participants	18	16
Number [percentage of participants]	61.1 339.4%	62.5 390.6%

3. Secondary Outcome

Title	Time to Complete Molecular Remission
Description	Number of months from randomization to molecular remission as defined by polymerase chain reaction negativity.
Time Frame	Up to 27 months

Outcome Measure Data

Analysis Population Description

Crossover participants were not analyzed for this outcome. This is as per the analysis plan written in this protocol.

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Patients will receive injections of interferon alfa and sargramostim once a day for 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm II. Interferon alfa: Given by injection Sargramostim: Given by injection	Patients will receive an injection of GM-K562 cell vaccine every 3 weeks for at least 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm I. NOTE: Study Arm B is not available to newly accrued and enrolled subjects based on the interim analysis directing all new subjects to the combination of Interferon + sargramostim (Arm A). GM-K562 cell vaccine: Given by injection
Measure Participants	18	16
Median (95% Confidence Interval) [months]	10	16.3

4. Secondary Outcome

Title	Disease-free Survival
Description	Median number of days to progression of disease in participants who stopped all treatment as directed by the protocol.
Time Frame	Up to 8 years

Outcome Measure Data

Analysis Population Description

Crossover participants were not analyzed for this outcome. This is as per the analysis plan written in this protocol.

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Patients will receive injections of interferon alfa and sargramostim once a day for 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm II. Interferon alfa: Given by injection Sargramostim: Given by injection	Patients will receive an injection of GM-K562 cell vaccine every 3 weeks for at least 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm I. NOTE: Study Arm B is not available to newly accrued and enrolled subjects based on the interim analysis directing all new subjects to the combination of Interferon + sargramostim (Arm A). GM-K562 cell vaccine: Given by injection
Measure Participants	18	16
Median (Full Range) [days]	82	98

5. Secondary Outcome

Title	Early Discontinuation
Description	Number of participants unable to complete protocol-specified treatment due to toxicity.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

This outcome includes all participants who were either started on an arm or crossed over to an arm.

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Patients will receive injections of interferon alfa and sargramostim once a day for 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm II. Interferon alfa: Given by injection Sargramostim: Given by injection	Patients will receive an injection of GM-K562 cell vaccine every 3 weeks for at least 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm I. NOTE: Study Arm B is not available to newly accrued and enrolled subjects based on the interim analysis directing all new subjects to the combination of Interferon + sargramostim (Arm A). GM-K562 cell vaccine: Given by injection
Measure Participants	30	25
Count of Participants [Participants]	10 55.6%	0 0%

Adverse Events

Time Frame	Up to 2 years
Adverse Event Reporting Description	Adverse events were collected monthly for up to two years.
Arm/Group Title	Arm A		Arm B
Arm/Group Description	Patients will receive injections of interferon alfa and sargramostim once a day for 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm II. Interferon alfa: Given by injection Sargramostim: Given by injection		Patients will receive an injection of GM-K562 cell vaccine every 3 weeks for at least 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm I. NOTE: Study Arm B is not available to newly accrued and enrolled subjects based on the interim analysis directing all new subjects to the combination of Interferon + sargramostim (Arm A). GM-K562 cell vaccine: Given by injection
All Cause Mortality
	Arm A		Arm B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/25 (0%)
Serious Adverse Events
	Arm A		Arm B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/30 (6.7%)		0/25 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
New malignancy - breast cancer	1/30 (3.3%)	1	0/25 (0%)	0
Vascular disorders
Deep vein thrombosis	1/30 (3.3%)	1	0/25 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm A		Arm B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/30 (100%)		25/25 (100%)
Blood and lymphatic system disorders
Edema	12/30 (40%)	19	10/25 (40%)	17
Hidradentitis	1/30 (3.3%)	1	1/25 (4%)	1
Cardiac disorders
Hypertension	1/30 (3.3%)	1	3/25 (12%)	3
Eye disorders
Conjunctivitis	2/30 (6.7%)	3	1/25 (4%)	1
Watery eyes	2/30 (6.7%)	2	2/25 (8%)	3
Gastrointestinal disorders
Acid reflux	1/30 (3.3%)	1	3/25 (12%)	4
Constipation	2/30 (6.7%)	3	1/25 (4%)	1
Diarrhea	7/30 (23.3%)	11	4/25 (16%)	6
Indigestion	2/30 (6.7%)	2	0/25 (0%)	0
Nausea	11/30 (36.7%)	11	5/25 (20%)	5
Pain - abdomen	3/30 (10%)	4	1/25 (4%)	2
Pain - throat	4/30 (13.3%)	4	7/25 (28%)	9
Vomiting	2/30 (6.7%)	2	4/25 (16%)	4
Xerostomia	2/30 (6.7%)	2	2/25 (8%)	2
General disorders
Alopecia	4/30 (13.3%)	4	3/25 (12%)	3
Anorexia	6/30 (20%)	7	0/25 (0%)	0
Chills	2/30 (6.7%)	2	1/25 (4%)	1
Dehydration	1/30 (3.3%)	1	2/25 (8%)	2
Fatigue	19/30 (63.3%)	32	15/25 (60%)	34
Flu-like symptoms	18/30 (60%)	28	6/25 (24%)	8
Insomnia	6/30 (20%)	6	0/25 (0%)	0
Malaise	1/30 (3.3%)	1	1/25 (4%)	1
Night sweats	3/30 (10%)	3	1/25 (4%)	1
Pain - ear	2/30 (6.7%)	2	0/25 (0%)	0
Pain - generalized	4/30 (13.3%)	4	3/25 (12%)	3
Pain - head	8/30 (26.7%)	12	8/25 (32%)	19
Rigors	2/30 (6.7%)	5	0/25 (0%)	0
Weight gain	1/30 (3.3%)	1	2/25 (8%)	2
Immune system disorders
Adenopathy	5/30 (16.7%)	5	3/25 (12%)	4
Allergic reaction	1/30 (3.3%)	1	1/25 (4%)	2
Injection site reaction	15/30 (50%)	23	25/25 (100%)	426
Seasonal allergies	1/30 (3.3%)	1	1/25 (4%)	1
Infections and infestations
Fever	5/30 (16.7%)	9	5/25 (20%)	8
Gastroenteritis	4/30 (13.3%)	4	5/25 (20%)	5
Urinary tract infection	0/30 (0%)	0	4/25 (16%)	4
Infection - sinus	5/30 (16.7%)	7	9/25 (36%)	12
Infection - upper respiratory	3/30 (10%)	3	4/25 (16%)	6
Viral infection	2/30 (6.7%)	2	2/25 (8%)	2
Investigations
ALT increased	8/30 (26.7%)	17	3/25 (12%)	5
Anemia	6/30 (20%)	12	5/25 (20%)	7
AST increased	7/30 (23.3%)	10	8/25 (32%)	13
Hyperglycemia	6/30 (20%)	10	5/25 (20%)	6
Hyperuricemia	4/30 (13.3%)	4	1/25 (4%)	1
Hypoalbuminemia	3/30 (10%)	4	0/25 (0%)	0
Hypocalcemia	6/30 (20%)	8	2/25 (8%)	3
Hypoglycemia	1/30 (3.3%)	1	3/25 (12%)	3
Hypokalemia	4/30 (13.3%)	8	2/25 (8%)	3
Leukopenia	5/30 (16.7%)	14	8/25 (32%)	15
Lymphopenia	7/30 (23.3%)	11	3/25 (12%)	4
Thrombocytopenia	4/30 (13.3%)	9	2/25 (8%)	4
Musculoskeletal and connective tissue disorders
Arthralgia	2/30 (6.7%)	3	1/25 (4%)	1
Myalgia	7/30 (23.3%)	9	3/25 (12%)	4
Pain - back	5/30 (16.7%)	7	0/25 (0%)	0
Pain - bone	3/30 (10%)	3	2/25 (8%)	8
Pain - leg	6/30 (20%)	8	0/25 (0%)	0
Ankle sprain	1/30 (3.3%)	1	1/25 (4%)	1
Nervous system disorders
Dizziness	3/30 (10%)	5	3/25 (12%)	3
Lightheadedness	0/30 (0%)	0	2/25 (8%)	2
Migraine	0/30 (0%)	0	2/25 (8%)	2
Weakness	1/30 (3.3%)	1	1/25 (4%)	1
Psychiatric disorders
Depression	2/30 (6.7%)	2	1/25 (4%)	2
Reproductive system and breast disorders
Menstrual cycle changes	4/30 (13.3%)	4	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
Bronchitis	3/30 (10%)	3	2/25 (8%)	2
Cough	4/30 (13.3%)	4	6/25 (24%)	7
Dyspnea	4/30 (13.3%)	5	3/25 (12%)	4
Nasal congestion	3/30 (10%)	4	7/25 (28%)	9
Nasal drip	2/30 (6.7%)	2	3/25 (12%)	4
Post-nasal drip	1/30 (3.3%)	2	2/25 (8%)	2
Skin and subcutaneous tissue disorders
Itching	2/30 (6.7%)	2	0/25 (0%)	0
Pigmentation changes	1/30 (3.3%)	1	2/25 (8%)	2
Eye swelling	1/30 (3.3%)	1	1/25 (4%)	1
Rash	10/30 (33.3%)	12	6/25 (24%)	6
Xerosis	1/30 (3.3%)	1	1/25 (4%)	1

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.