Imatinib Mesylate in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Who Have Received Chemotherapy

• Sponsor: Case Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00509093
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 32
• Locations: 4
• Arm: 1
• Duration (Months): 78.2
• Patients Per Site: 8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well imatinib mesylate works in treating patients with newly diagnosed acute myeloid leukemia who have received chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: imatinib mesylate; Genetic: gene expression analysis; Genetic: mutation analysis; Genetic: polymerase chain reaction; Other: flow cytometry; Procedure: biopsy	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To determine whether adding imatinib mesylate as maintenance therapy improves progression-free survival in patients with c-kit positive acute myeloid leukemia (AML) compared with historical controls.

Secondary

• To assess the feasibility of administering imatinib mesylate as maintenance therapy after the completion of induction and consolidation therapy in these patients.

• To evaluate potential mechanisms of relapse/resistance in c-kit positive AML by examining multidrug resistance gene expression and AF1q gene expression and to determine whether these levels correlate with c-kit expression.

OUTLINE: This is a multicenter study.

Patients receive oral imatinib mesylate once daily for up to 12 months.

Bone marrow and peripheral blood are collected at baseline. Laboratory endpoints are evaluated by flow cytometry; mutation and gene analysis by PCR.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Imatinib Mesylate (Gleevec) as Maintenance Therapy After Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed C-kit Positive Acute Myeloid Leukemia
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: May 9, 2014
• Actual Study Completion Date: Apr 9, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Imatinib Mesylate

Drug: imatinib mesylate; Patients will receive treatment with imatinib mesylate at a dose of 600 mg by mouth once a day for 12 months. The study dose can be split but the dose of 600 mg must be given within a 12 hour period.; Other Names: Gleevec ; Genetic: gene expression analysis; Multidrug resistance genes: These studies will include: MDR1, MRP1, LRP, and BCRP. Bone marrow blocks or cut slides will be sent to Duke on the diagnostic AML samples. DNA will be eluted from the samples so that the above genes can be analyzed.; Other Names: MRD ; Genetic: mutation analysis; FLT3 mutation analysis (on bone marrow aspirate or peripheral blood): These analyses will be performed by pathology at the time of diagnosis, at the participating institution. Samples will be analyzed for the FLT3 ITD and/or D835 mutation by PCR.; Other Names: FLT3 ; Genetic: polymerase chain reaction; AF1q gene analysis (on bone marrow aspirate); Other Names: AF1Q gene analysis ; Other: flow cytometry; C-kit MFI on AML samples will be calculated by using a CD45/ orthogonal light scatter gate to isolate blasts. The MFI will be calculated as the c-kit mean channel number (MCN) of the blasts/ MCN auto fluorescence.; Other Names: C-kit MFI, CD117 ; Procedure: biopsy; Diagnostic bone marrow biopsy/aspirate must be done within 3 weeks of registration documenting complete remission; Other Names: bone marrow biopsy/aspirate

Outcome Measures

Primary Outcome Measures

1. Median Progression-free Survival (PFS) for Patients Less Than 60 Years of Age [up to 5 years from the End of Treatment]

   PFS measured from the date of Complete Response (CR) to the date of relapse or death. Progression defined as any of the following event: progression to accelerated phase or blast crisis, death, loss of CHR or MCyR, or in patients not achieving a CHR an increasing WBC despite appropriate therapeutic management This outcome will be reported as median progression-free survival in months for participants less than 60 years of age.

2. Progression-free Survival for Patients 60 Years of Age and Older [up to 5 years from the End of Treatment]

   Progression free survival will be measured from the date of Complete Response (CR) to the date of relapse or death.

3. Percent of Participants Less Than 60 Years of Age With PFS at 8 and 13 Months Post-treatment [at 8 and 13 months after treatment.]

   Percent of participants less than 60 years of age with PFS at 8 and 13 months post-treatment

4. Percent of Participants 60 Years of Age or Older With PFS at 8 and 13 Months Post-treatment [at 8 and 13 months after treatment.]

   Percent of participants 60 years of age or older with PFS at 8 and 13 months post-treatment

Secondary Outcome Measures

1. Toxicity as Measured by NCI CTC v. 3.0 [13 months from start of treatment]

   Number of patients (%) experiencing an adverse event See adverse events section for details

Other Outcome Measures

1. Correlation of C-kit Expression With Multidrug Resistance Gene Expression (MDR1, MRP1, LRP, and BCRP) and AF1q Expression [24 months]

Eligibility Criteria

Criteria

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

INCLUSION CRITERIA

• Diagnostic bone marrow aspirate/ biopsy or peripheral blood confirming AML.

• At the time of diagnosis, patients must have c-kit (also known as CD117) positive AML (20% or more of the blasts express c-kit[CD117]).

• A flow scattergram (from the diagnostic AML specimen) must be available to calculate a c-kit MFI.

• Patients must have received standard induction chemotherapy with ADE (cytarabine, daunorubicin, and etoposide) or with 7+3 (7 days of cytarabine continuous infusion and 3 days of an anthracycline (idarubicin, daunorubicin, or mitoxantrone). Patients with persistent leukemia on a Day 10-28 marrow may have received a second course of chemotherapy.

• After the completion of induction therapy, patients must have attained a complete remission based on blood count recovery (neutrophil count ≥ 1,000/µL, platelet count ≥ 100,000/µL), and bone marrow aspirate and biopsy (< 5% myeloblasts).

• For patients < 60 years of age, patients must have received at least 2 courses of post-remission therapy with at least intermediate dose (400 mg/m2/day). *Patients with t(8;21) or inversion 16 at the time of diagnosis must have received at least 2 courses of high dose cytarabine. For patients > or = 60 years of age, patients must have received 1 course of post-remission therapy (the type of chemotherapy will not be specified).

• Patients must be registered on this study (maintenance Imatinib mesylate) within 60 days of the last dose of post-remission therapy.

• A bone marrow aspirate and/or biopsy must be done within 3 weeks of registration documenting CR.

• Women of childbearing potential and sexually active males must use an effective method of contraception.

• Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.

• ECOG Performance Status 0-2.

• Creatinine must be ≤ 1.5 x upper limit of normal.

• Total bilirubin must be ≤ 2 mg/dl and AST and ALT must be ≤ 2 times the upper limit of normal.

• Previous treatment-related toxicities must have resolved to ≤ Grade 1 excluding alopecia.

• Written, voluntary informed consent.

EXCLUSION CRITERIA

• Acute promyelocytic leukemia.

• Patients with an autologous or allogeneic bone marrow transplant.

• History of HIV.

• Pregnant or breast-feeding.

• Serious or poorly controlled medical conditions that would interfere with the protocol.

• At the time of study entry, any medications which could significantly interact with imatinib mesylate must be discontinued.

• Patients with active extramedullary disease are not eligible.

• Patient has received any other investigational agents within 28 days of first day of study drug dosing.

• Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.

• Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)

• Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).

• Patient previously received radiotherapy to ≥ 25 % of the bone marrow

• Patient had a major surgery within 2 weeks prior to study entry.

• Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
2	Duke University Medical Center	Durham	North Carolina	United States	27710
3	University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106-5065
4	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• Case Comprehensive Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Anjali Advani, MD, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
• Principal Investigator: Brenda Cooper, MD, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00509093
• Other Study ID Numbers: CASE4906; P30CA043703; CASE4906; AUS259; NCI-2010-01198
• First Posted: Jul 31, 2007
• Last Update Posted: Mar 17, 2020
• Last Verified: Mar 1, 2020

• Keywords provided by Case Comprehensive Cancer Center: adult acute minimally differentiated myeloid leukemia (M0); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myelomonocytic leukemia (M4); adult acute megakaryoblastic leukemia (M7); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b); adult acute basophilic leukemia; adult acute eosinophilic leukemia; adult acute myeloid leukemia in remission
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Imatinib Mesylate

Study Results

Participant Flow

Arm/Group Title	Imatinib Mesylate
Arm/Group Description	Imatinib mesylate: Participants will receive treatment with imatinib mesylate at a dose of 600 mg by mouth once a day for 12 months. Study dose can be split but the dose of 600 mg must be given within a 12 hour period. Gene expression analysis: Multidrug resistance genes: These studies will include: MDR1, MRP1, LRP, and BCRP. Bone marrow blocks or cut slides will be sent to Duke on the diagnostic AML samples. DNA will be eluted from the samples so that the above genes can be analyzed. Mutation analysis: FLT3 mutation analysis (on bone marrow aspirate or peripheral blood): These analyses will be performed by pathology at the time of diagnosis, at the participating institution. Samples will be analyzed for the FLT3 ITD and/or D835 mutation by PCR. PCR: AF1q gene analysis (on bone marrow aspirate) Flow cytometry: C-kit MFI on AML samples will be calculated by using a CD45/ orthogonal light scatter gate to isolate blasts. The MFI will be calculated a
Period Title: Overall Study
STARTED	32
COMPLETED	8
NOT COMPLETED	24

Baseline Characteristics

Arm/Group Title	Imatinib Mesylate
Arm/Group Description	Imatinib mesylate: Participants will receive treatment with imatinib mesylate at a dose of 600 mg by mouth once a day for 12 months. Study dose can be split but the dose of 600 mg must be given within a 12 hour period. Gene expression analysis: Multidrug resistance genes: These studies will include: MDR1, MRP1, LRP, and BCRP. Bone marrow blocks or cut slides will be sent to Duke on the diagnostic AML samples. DNA will be eluted from the samples so that the above genes can be analyzed. Mutation analysis: FLT3 mutation analysis (on bone marrow aspirate or peripheral blood): These analyses will be performed by pathology at the time of diagnosis, at the participating institution. Samples will be analyzed for the FLT3 ITD and/or D835 mutation by PCR. PCR: AF1q gene analysis (on bone marrow aspirate) Flow cytometry: C-kit MFI on AML samples will be calculated by using a CD45/ orthogonal light scatter gate to isolate blasts. The MFI will be calculated a
Overall Participants	32
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.2 (16.0)
Age, Customized (Count of Participants)
20-29 years	4 12.5%
30-39 years	3 9.4%
40-49 years	4 12.5%
50-59 years	10 31.3%
60-69 years	4 12.5%
70-79 years	6 18.8%
80-89 years	1 3.1%
Sex: Female, Male (Count of Participants)
Female	18 56.3%
Male	14 43.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	32 100%
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	2 6.3%
White	30 93.8%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	32 100%

Outcome Measures

1. Primary Outcome

Title	Median Progression-free Survival (PFS) for Patients Less Than 60 Years of Age
Description	PFS measured from the date of Complete Response (CR) to the date of relapse or death. Progression defined as any of the following event: progression to accelerated phase or blast crisis, death, loss of CHR or MCyR, or in patients not achieving a CHR an increasing WBC despite appropriate therapeutic management This outcome will be reported as median progression-free survival in months for participants less than 60 years of age.
Time Frame	up to 5 years from the End of Treatment

Outcome Measure Data

Analysis Population Description

All participants less than 60 years of age

Arm/Group Title	Imatinib Mesylate
Arm/Group Description	Imatinib mesylate: Participants will receive treatment with imatinib mesylate at a dose of 600 mg by mouth once a day for 12 months. Study dose can be split but the dose of 600 mg must be given within a 12 hour period. Gene expression analysis: Multidrug resistance genes: These studies will include: MDR1, MRP1, LRP, and BCRP. Bone marrow blocks or cut slides will be sent to Duke on the diagnostic AML samples. DNA will be eluted from the samples so that the above genes can be analyzed. Mutation analysis: FLT3 mutation analysis (on bone marrow aspirate or peripheral blood): These analyses will be performed by pathology at the time of diagnosis, at the participating institution. Samples will be analyzed for the FLT3 ITD and/or D835 mutation by PCR. PCR: AF1q gene analysis (on bone marrow aspirate) Flow cytometry: C-kit MFI on AML samples will be calculated by using a CD45/ orthogonal light scatter gate to isolate blasts. The MFI will be calculated a
Measure Participants	21
Median (Inter-Quartile Range) [months]	52.1

2. Primary Outcome

Title	Progression-free Survival for Patients 60 Years of Age and Older
Description	Progression free survival will be measured from the date of Complete Response (CR) to the date of relapse or death.
Time Frame	up to 5 years from the End of Treatment

Outcome Measure Data

Analysis Population Description

All participants 60 years or older.

Arm/Group Title	Imatinib Mesylate
Arm/Group Description	Imatinib mesylate: Participants will receive treatment with imatinib mesylate at a dose of 600 mg by mouth once a day for 12 months. Study dose can be split but the dose of 600 mg must be given within a 12 hour period. Gene expression analysis: Multidrug resistance genes: These studies will include: MDR1, MRP1, LRP, and BCRP. Bone marrow blocks or cut slides will be sent to Duke on the diagnostic AML samples. DNA will be eluted from the samples so that the above genes can be analyzed. Mutation analysis: FLT3 mutation analysis (on bone marrow aspirate or peripheral blood): These analyses will be performed by pathology at the time of diagnosis, at the participating institution. Samples will be analyzed for the FLT3 ITD and/or D835 mutation by PCR. PCR: AF1q gene analysis (on bone marrow aspirate) Flow cytometry: C-kit MFI on AML samples will be calculated by using a CD45/ orthogonal light scatter gate to isolate blasts. The MFI will be calculated a
Measure Participants	11
Median (Inter-Quartile Range) [months]	10.7

3. Primary Outcome

Title	Percent of Participants Less Than 60 Years of Age With PFS at 8 and 13 Months Post-treatment
Description	Percent of participants less than 60 years of age with PFS at 8 and 13 months post-treatment
Time Frame	at 8 and 13 months after treatment.

Outcome Measure Data

Analysis Population Description

All participants less than 60 years of age

Arm/Group Title	Imatinib Mesylate
Arm/Group Description	Imatinib mesylate: Participants will receive treatment with imatinib mesylate at a dose of 600 mg by mouth once a day for 12 months. Study dose can be split but the dose of 600 mg must be given within a 12 hour period. Gene expression analysis: Multidrug resistance genes: These studies will include: MDR1, MRP1, LRP, and BCRP. Bone marrow blocks or cut slides will be sent to Duke on the diagnostic AML samples. DNA will be eluted from the samples so that the above genes can be analyzed. Mutation analysis: FLT3 mutation analysis (on bone marrow aspirate or peripheral blood): These analyses will be performed by pathology at the time of diagnosis, at the participating institution. Samples will be analyzed for the FLT3 ITD and/or D835 mutation by PCR. PCR: AF1q gene analysis (on bone marrow aspirate) Flow cytometry: C-kit MFI on AML samples will be calculated by using a CD45/ orthogonal light scatter gate to isolate blasts. The MFI will be calculated a
Measure Participants	21
at 8 months post treatment	76.2 238.1%
at 13 months post treatment	54.5 170.3%

4. Primary Outcome

Title	Percent of Participants 60 Years of Age or Older With PFS at 8 and 13 Months Post-treatment
Description	Percent of participants 60 years of age or older with PFS at 8 and 13 months post-treatment
Time Frame	at 8 and 13 months after treatment.

Outcome Measure Data

Analysis Population Description

All participants 60 years or older

Arm/Group Title	Imatinib Mesylate
Arm/Group Description	Imatinib mesylate: Participants will receive treatment with imatinib mesylate at a dose of 600 mg by mouth once a day for 12 months. Study dose can be split but the dose of 600 mg must be given within a 12 hour period. Gene expression analysis: Multidrug resistance genes: These studies will include: MDR1, MRP1, LRP, and BCRP. Bone marrow blocks or cut slides will be sent to Duke on the diagnostic AML samples. DNA will be eluted from the samples so that the above genes can be analyzed. Mutation analysis: FLT3 mutation analysis (on bone marrow aspirate or peripheral blood): These analyses will be performed by pathology at the time of diagnosis, at the participating institution. Samples will be analyzed for the FLT3 ITD and/or D835 mutation by PCR. PCR: AF1q gene analysis (on bone marrow aspirate) Flow cytometry: C-kit MFI on AML samples will be calculated by using a CD45/ orthogonal light scatter gate to isolate blasts. The MFI will be calculated a
Measure Participants	11
at 8 months post treatment	61.9 193.4%
at 13 months post treatment	36.4 113.8%

5. Secondary Outcome

Title	Toxicity as Measured by NCI CTC v. 3.0
Description	Number of patients (%) experiencing an adverse event See adverse events section for details
Time Frame	13 months from start of treatment

Outcome Measure Data

Analysis Population Description

Number of patients (%) experiencing the adverse event

Arm/Group Title	Imatinib Mesylate
Arm/Group Description	Imatinib mesylate: Participants will receive treatment with imatinib mesylate at a dose of 600 mg by mouth once a day for 12 months. Study dose can be split but the dose of 600 mg must be given within a 12 hour period. Gene expression analysis: Multidrug resistance genes: These studies will include: MDR1, MRP1, LRP, and BCRP. Bone marrow blocks or cut slides will be sent to Duke on the diagnostic AML samples. DNA will be eluted from the samples so that the above genes can be analyzed. Mutation analysis: FLT3 mutation analysis (on bone marrow aspirate or peripheral blood): These analyses will be performed by pathology at the time of diagnosis, at the participating institution. Samples will be analyzed for the FLT3 ITD and/or D835 mutation by PCR. PCR: AF1q gene analysis (on bone marrow aspirate) Flow cytometry: C-kit MFI on AML samples will be calculated by using a CD45/ orthogonal light scatter gate to isolate blasts. The MFI will be calculated a
Measure Participants	32
Count of Participants [Participants]	30 93.8%

6. Other Pre-specified Outcome

Title	Correlation of C-kit Expression With Multidrug Resistance Gene Expression (MDR1, MRP1, LRP, and BCRP) and AF1q Expression
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Up to four weeks after off-study date, an average of 2.6 years
Arm/Group Title	Imatinib Mesylate
Arm/Group Description	Imatinib mesylate: Participants will receive treatment with imatinib mesylate at a dose of 600 mg by mouth once a day for 12 months. Study dose can be split but the dose of 600 mg must be given within a 12 hour period. Gene expression analysis: Multidrug resistance genes: These studies will include: MDR1, MRP1, LRP, and BCRP. Bone marrow blocks or cut slides will be sent to Duke on the diagnostic AML samples. DNA will be eluted from the samples so that the above genes can be analyzed. Mutation analysis: FLT3 mutation analysis (on bone marrow aspirate or peripheral blood): These analyses will be performed by pathology at the time of diagnosis, at the participating institution. Samples will be analyzed for the FLT3 ITD and/or D835 mutation by PCR. PCR: AF1q gene analysis (on bone marrow aspirate) Flow cytometry: C-kit MFI on AML samples will be calculated by using a CD45/ orthogonal light scatter gate to isolate blasts. The MFI will be calculated a
All Cause Mortality
	Imatinib Mesylate
	Affected / at Risk (%)	# Events
Total	20/32 (62.5%)
Serious Adverse Events
	Imatinib Mesylate
	Affected / at Risk (%)	# Events
Total	5/32 (15.6%)
Blood and lymphatic system disorders
Neutropenia	1/32 (3.1%)	1
Cardiac disorders
Hypotension	1/32 (3.1%)	1
Pericardial effusion (non-malignant)	1/32 (3.1%)	2
Gastrointestinal disorders
Diarrhea	1/32 (3.1%)	2
Infections and infestations
Infection with unknown ANC - Blood	1/32 (3.1%)	1
Nervous system disorders
Seizure	1/32 (3.1%)	1
Pain - Bone	1/32 (3.1%)	1
Pain - Cardiac/heart	1/32 (3.1%)	1
Pain - Joint	1/32 (3.1%)	1
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome (ARDS)	1/32 (3.1%)	1
Atelectasis	1/32 (3.1%)	1
Pleural effusion (non-malignant)	1/32 (3.1%)	1
Skin and subcutaneous tissue disorders
Urticaria (hives, welts, wheals)	1/32 (3.1%)	1
Other (Not Including Serious) Adverse Events
	Imatinib Mesylate
	Affected / at Risk (%)	# Events
Total	30/32 (93.8%)
Blood and lymphatic system disorders
Hemoglobin	12/32 (37.5%)	35
Hemolysis (e.g., immune hemolytic anemia, drug-related hemolysis)	1/32 (3.1%)	1
Leukocytes (total WBC)	14/32 (43.8%)	41
Lymphopenia	6/32 (18.8%)	47
Neutrophils/granulocytes (ANC/AGC)	14/32 (43.8%)	30
Platelets	18/32 (56.3%)	53
INR (International Normalized Ratio of prothrombin time)	1/32 (3.1%)	2
Edema: trunk/genital	1/32 (3.1%)	1
Edema: viscera	1/32 (3.1%)	1
"Clear Liquid" coming from left ear	1/32 (3.1%)	1
Small Preauricular Left Node	1/32 (3.1%)	1
Albumin, serum-low (hypoalbuminemia)	1/32 (3.1%)	1
Alkaline phosphatase	4/32 (12.5%)	5
Cardiac disorders
Hypotension	1/32 (3.1%)	1
Ear and labyrinth disorders
Fullness in Right Ear	1/32 (3.1%)	1
Eye disorders
Optic disc edema	1/32 (3.1%)	1
Vision-blurred vision	1/32 (3.1%)	1
Pain - Abdomen NOS	4/32 (12.5%)	5
Pain - Back	1/32 (3.1%)	1
Gastrointestinal disorders
Diarrhea	13/32 (40.6%)	20
Esophagitis	1/32 (3.1%)	1
Flatulence	1/32 (3.1%)	1
Upset Stomach	1/32 (3.1%)	1
gastroenteritis	1/32 (3.1%)	1
Heartburn/dyspepsia	3/32 (9.4%)	3
Nausea	17/32 (53.1%)	30
Taste alteration (dysgeusia)	1/32 (3.1%)	1
Vomiting	7/32 (21.9%)	8
Hemorrhage, GU - Urinary NOS	1/32 (3.1%)	1
Infected cyst in left groin area; draining pus	1/32 (3.1%)	1
General disorders
aches at base of skull	1/32 (3.1%)	1
aural stuffiness	1/32 (3.1%)	1
body aches and chills	1/32 (3.1%)	1
Decreased total protein in blood	1/32 (3.1%)	1
Dyspnea	1/32 (3.1%)	1
edema in extremities	1/32 (3.1%)	1
emesis	2/32 (6.3%)	2
episode of flu	1/32 (3.1%)	11
facial edema	1/32 (3.1%)	1
facial itching	1/32 (3.1%)	1
hand stiffness	1/32 (3.1%)	1
Edema to face and legs	1/32 (3.1%)	1
Insomnia	5/32 (15.6%)	5
intermittent rash	1/32 (3.1%)	1
loose stool	1/32 (3.1%)	1
lower extremity edema	1/32 (3.1%)	1
mild edema in general and particularly in eye area	1/32 (3.1%)	1
mild swelling/edema	1/32 (3.1%)	1
mild tingling and discomfort rt lower extremity	1/32 (3.1%)	1
muscle cramping	1/32 (3.1%)	1
nasal congestion	1/32 (3.1%)	1
nausea	2/32 (6.3%)	2
occasional mild sore throat	1/32 (3.1%)	1
periorbital edema	1/32 (3.1%)	1
peri-orbital itchiness	1/32 (3.1%)	1
Periorbital swelling	1/32 (3.1%)	1
post nasal discharge	1/32 (3.1%)	1
post-herpetic neuralgia	1/32 (3.1%)	1
puffiness of eyes	1/32 (3.1%)	1
right heel pain	1/32 (3.1%)	1
right shoulder discomfort	1/32 (3.1%)	1
sore throat	1/32 (3.1%)	1
soreness in left ear	1/32 (3.1%)	1
stiff neck	1/32 (3.1%)	1
stomach burning	1/32 (3.1%)	1
upper back discomfort	1/32 (3.1%)	1
upper respiratory infection	1/32 (3.1%)	1
Fatigue (asthenia, lethargy, malaise)	13/32 (40.6%)	17
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	1/32 (3.1%)	1
Sweating (diaphoresis)	1/32 (3.1%)	1
Weight gain	6/32 (18.8%)	6
Bruising (in absence of Grade 3 or 4 thrombocytopenia)	1/32 (3.1%)	1
Dry skin	1/32 (3.1%)	1
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Conjunctiva	1/32 (3.1%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils - Lung (pneumonia)	1/32 (3.1%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils - Nerve-peripheral	1/32 (3.1%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils - Sinus	1/32 (3.1%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils - Urinary tract NOS	1/32 (3.1%)	1
Infection with unknown ANC - Urinary tract NOS	1/32 (3.1%)	1
Edema: head and neck	8/32 (25%)	9
Edema: limb	12/32 (37.5%)	12
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	4/32 (12.5%)	7
AST, SGOT(serum glutamic oxaloacetic transaminase)	5/32 (15.6%)	7
Bilirubin (hyperbilirubinemia)	2/32 (6.3%)	3
Calcium, serum-low (hypocalcemia)	3/32 (9.4%)	5
Creatinine	2/32 (6.3%)	2
Glucose, serum-high (hyperglycemia)	4/32 (12.5%)	6
Magnesium, serum-low (hypomagnesemia)	1/32 (3.1%)	1
Potassium, serum-high (hyperkalemia)	1/32 (3.1%)	1
Potassium, serum-low (hypokalemia)	2/32 (6.3%)	2
Sodium, serum-low (hyponatremia)	3/32 (9.4%)	4
Muscle weakness, generalized or specific area (not due to neuropathy) - Extraocular	1/32 (3.1%)	1
Dizziness	2/32 (6.3%)	2
Musculoskeletal and connective tissue disorders
Neuropathy: sensory	2/32 (6.3%)	2
Nervous system disorders
Syncope (fainting)	1/32 (3.1%)	1
Mood alteration - Anxiety	2/32 (6.3%)	2
Mood alteration - Depression	1/32 (3.1%)	1
Pain - Bone	1/32 (3.1%)	1
Pain - External ear	1/32 (3.1%)	1
Pain - Extremity-limb	2/32 (6.3%)	2
Pain - Head/headache	3/32 (9.4%)	3
Pain - Joint	3/32 (9.4%)	3
Pain - Muscle	1/32 (3.1%)	1
Mild Generalized Body Aches	1/32 (3.1%)	1
rt ankle pain	1/32 (3.1%)	1
chronic hip pain	1/32 (3.1%)	1
lower extremity pain	1/32 (3.1%)	1
mild cramping	1/32 (3.1%)	1
sciatica	1/32 (3.1%)	2
Pain - Pain NOS	1/32 (3.1%)	1
Pain - Stomach	2/32 (6.3%)	6
Pain - Throat/pharynx/larynx	1/32 (3.1%)	1
Bronchospasm, wheezing	1/32 (3.1%)	1
Cough	2/32 (6.3%)	2
Psychiatric disorders
Eye Swelling and Redness	1/32 (3.1%)	1
occasional burning of eyes	1/32 (3.1%)	1
Renal and urinary disorders
Infection with normal ANC or Grade 1 or 2 neutrophils - Bladder (urinary)	1/32 (3.1%)	1
Increased Bladder Pressure	1/32 (3.1%)	1
Reproductive system and breast disorders
No Menstrual	1/32 (3.1%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	3/32 (9.4%)	4
Nasal cavity/paranasal sinus reactions	1/32 (3.1%)	1
Nasal Congestion	1/32 (3.1%)	1
Skin and subcutaneous tissue disorders
blisters on feet	1/32 (3.1%)	1
discoloration of face	1/32 (3.1%)	1
Dry skin	1/32 (3.1%)	1
Hair loss/alopecia (scalp or body)	1/32 (3.1%)	1
Nail changes	2/32 (6.3%)	2
Pruritus/itching	2/32 (6.3%)	2
Rash/desquamation	6/32 (18.8%)	8
Rash: acne/acneiform	1/32 (3.1%)	1
Rash: dermatitis associated with radiation - Chemoradiation	3/32 (9.4%)	5
Anorexia	2/32 (6.3%)	3
Constipation	2/32 (6.3%)	2

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.