Study of Oral Dasatinib in Subjects With Myelodysplastic Syndrome (MDS) and Excess Marrow Blasts

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00624585
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 18
• Location: 1
• Arm: 1
• Duration (Months): 51
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The main purpose of this study is to learn how patients with myelodysplastic syndrome (MDS) respond to the study drug dasatinib. The study drug, dasatinib, has been approved by the U.S. Food and Drug Administration (FDA) for treatment of leukemia, but has not been approved for the treatment of other kinds of cancer. The use of dasatinib in this study is considered experimental.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes	Drug: Dasatinib	N/A

Detailed Description

Study Core Period:

The first 16 weeks after the initial dose of dasatinib is called the Study Core Period. Patients who are eligible and chose to participate in this study should expect to take 100 mg of dasatinib daily for 8 weeks. If the study doctor believes that they have not achieved a partial response after 8 weeks of treatment, the dose may be increased to 150 mg per day. The study doctor may lower the dosage of dasatinib if the 100 mg treatment is too strong. If the lower dose of dasatinib is still too strong, the study doctor may decide to take the patient off of the study. The patient will continue to receive supportive care as needed during the duration of the trial as well as after completion of the trial.

During the Study Core Period, participants will have a study visit every 4 weeks. Complete Blood Counts (CBCs) will be obtained every 2 weeks for study purposes and disease monitoring. Bone marrow aspiration and biopsy will be obtained at screening, and at 8 weeks and 16 weeks of treatment for response assessment. Additional bone marrow aspirations and biopsies may be obtained at any other time, to evaluate the disease process, at the doctor's judgment. A bone marrow aspirate and biopsy must be done at the time of study discontinuation.

Study Extension Period:

The time after the first 16 weeks of treatment is called the study extension period. If the patient is responding to the treatment, does not experience disease progression or any severe adverse events, the patient may continue dasatinib treatment for up to 48 weeks. If patients continue after 48 weeks, they will be asked to enroll in a separate extension study for future follow up.

During the Study Extension Period, participants will have a study visit every 4 weeks. Complete Blood Counts (CBCs) will be obtained every 2 or 4 weeks for study purposes and disease monitoring. Bone marrow aspiration and biopsy will be obtained every 16 weeks. A bone marrow aspirate and biopsy must be done at the time of study discontinuation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of Oral Dasatinib in Subjects With MDS and Excess Marrow Blasts
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Dasatinib Dose Escalation Patients will be started on dasatinib at a continuous oral daily dose of 100 mg per day. At 8 weeks, if the initial dose is well tolerated and patient has not achieved a partial response, the dose may be increased to 150 mg per day. All patients will be followed per protocol for a total core period of 16 weeks from the first dose. Responding patients will continue dasatinib treatment for up to 48 weeks in the absence of treatment failure, disease progression, limiting toxicity or death. Patients continuing after 48 weeks will be enrolled in a separate extension study for future follow up.

Drug: Dasatinib; DOSE ESCALATION OF DASATINIB AFTER 8 WEEKS IF ELIGIBLE Dose Level and Dose of dasatinib: Starting dose (1-8 weeks)= 100 mg orally (po) daily +1 (<8 weeks if no PR and well tolerated) = 150 mg po daily DOSE MODIFICATION OF DASATINIB Dose Level and Dose of dasatinib: Starting dose = 100 mg po daily -1 = 70 mg po daily -2 = 50 mg po daily OR Dose Level and Dose of dasatinib: Starting dose = 150 mg po daily -1 = 120 mg po daily -2 = 90 mg po daily -3 = 50 mg po daily; Other Names: SPRYCEL®

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Marrow Complete Remission (CR) [1 Year 4 Months]

   Complete remission (modified IWG); IWG = International MDS Working Group. Bone Marrow Response must last ≥4 weeks. Bone marrow evaluation: Bone marrow showing ≤5% myeloblasts with normal maturation of all cell lines.

Secondary Outcome Measures

1. Number of Participants With Hematologic Improvement [1 Year 4 Months]

   Hematologic improvement in platelets, red blood cell (RBC), neutrophils according to modified IWG Criteria; Cytogenetic response (modified IWG); Change in percentage of blasts in bone marrow and peripheral blood; Src-Tyr416 phosphorylation in medullary myeloblasts. Hematologic improvements must last ≥ 8 weeks.

2. Number of Participants With Partial Remission (PR) [1 Year 4 Months]

   Partial remission (PR) (modified IWG); IWG = International MDS Working Group. All of the CR criteria (if abnormal prior to treatment), except: Bone marrow evaluation: Blasts decreased by ≥ 50% over pretreatment but still >5%. Cellularity and morphology are not relevant.

3. Number of Participants With Stable Disease (SD) [1 Year 4 Months]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Documented diagnosis of MDS or Myeloproliferative Disorders (MPS/MPD) with blast percentage > 10% in bone marrow, MDS/AML with <30% blasts:

• MDS [all World Health Organization (WHO) types] with blast percentage > 10% in bone marrow

• Chronic myelomonocytic leukemia (CMML) with blast percentage > 10% in bone marrow

• Myelodysplastic / Myeloproliferative (MDS/MPD) syndromes with blast percentage > 10% in bone marrow

• Acute myeloid leukemia with Multilineage Dysplasia (MDS/AML) with <30% blasts and declined standard induction chemotherapy or deemed unfit for standard induction chemotherapy

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2

• Previous therapy with Azacitidine or Decitabine with last dose at least 2 months prior to first dose of dasatinib okay. Must be at least 4 weeks out from any previous investigational therapy.

• Adequate Organ Function

• Total bilirubin < 2.0 times institutional Upper Limit of Normal (ULN)

• Hepatic enzymes (AST, ALT) ≤ 2.5 times institutional ULN

• Serum Na, K+, Mg2+, Phosphate and Ca2+≥ Lower Limit of Normal (LLN) [low electrolyte levels must be repleted to all for entry]

• Serum Creatinine < 1.5 times ULN

• Prothrombin time (PT), partial thromboplastin time (PTT) Grade 0-1

• Able to take oral medication (Dasatinib must be swallowed whole. Tablets can be dissolved in juice and then put down an NG/G tube or drank as a solution)

• Women of childbearing potential (WOCBP) must have Negative serum or urine pregnancy test within 72 hours prior to start of study drug

• Persons of reproductive potential must agree to use adequate birth control throughout treatment and at least 4 weeks after study drug is stopped

• Signed written informed consent

Exclusion Criteria:

• White blood count (WBC) >50,000 off hydroxyurea for >72 hours

• Malignancy [other than the one treated in this study] requiring radiotherapy or systemic treatment within past 3 years

• Chemotherapy or any agent with activity in MDS or AML concurrent with the study.

• Chemotherapy for MDS or AML prior to enrollment not allowed other than Azacitidine or Decitabine >2 months prior to first dose

• Concurrent medical condition which may increase the risk of toxicity, including:

• Pleural or pericardial effusion

• Serious medical condition, unstable medical co-morbidity, psychiatric illness that will prevent subject from signing informed consent form or place them at unacceptable risk if they participate

• Cardiac Symptoms, including:

• Uncontrolled angina, congestive heart failure or myocardial infarction (MI) within 6 months

• Diagnosed congenital long QT syndrome

• History of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes)

• Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec)

• Hypokalemia or hypomagnesemia if cannot be corrected

• History of significant bleeding disorder unrelated to cancer, including:

• Congenital bleeding disorders

• Acquired bleeding disorder within 1 year

• Ongoing or recent (≤ 3 months) significant gastrointestinal bleeding

• Concomitant Medications, consider the following prohibitions:

• Drugs generally accepted to have risk of causing Torsades de Pointes(Must discontinue drug 7 days prior to starting dasatinib)

• Concomitant use of H2 blockers or proton pump inhibitors with dasatinib not recommended. Use of antacids should be considered in place of H2 blockers or proton pump inhibitors in patients receiving dasatinib therapy.

• On-going requirement for treatment with platelet function inhibitor or anti-coagulation.

• Must discontinue St. Johns Wort while receiving dasatinib therapy

• Must agree that intravenous (IV) bisphosphonates be withheld for first 8 weeks of Dasatinib therapy due to risk of hypocalcemia.

• May not be receiving any prohibited CYP3A4 inhibitors

• Women:

• Positive pregnancy test at baseline

• Pregnant or breastfeeding

• Prisoners or patients who are compulsorily detained for treatment of either psychiatric or physical (e.g., infectious) illness

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612

Sponsors and Collaborators

• H. Lee Moffitt Cancer Center and Research Institute
• Bristol-Myers Squibb

Investigators

• Principal Investigator: Alan List, M.D., H. Lee Moffitt Cancer Center and Research Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Moffitt Cancer Center Clinical Trials website

Publications

None provided.

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT00624585
• Other Study ID Numbers: MCC-15276; CA180-106
• First Posted: Feb 27, 2008
• Last Update Posted: Dec 16, 2013
• Last Verified: May 1, 2012

• Keywords provided by H. Lee Moffitt Cancer Center and Research Institute: MDS; MDS/MPD; MDS/AML; CMML; Excess Marrow Blasts
• Additional relevant MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome; Dasatinib

Study Results

Participant Flow

Recruitment Details	Patients with Int-2 or High risk MDS according to International Prognostic Scoring System (IPSS) score. All World Health Organization (WHO) subtypes of Myelodysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia (CMML), or Myelodysplastic / Myeloproliferative (MDS/MPD) were allowed.
Pre-assignment Detail	Acute Myeloid Leukemia Multilineage Dysplasia (MDS/AML) with <30% blasts (RAEB-t) who either declined or were deemed unfit for induction chemotherapy were also eligible. Exclusion criteria were WBC >50,000 off hydroxyurea, another malignancy requiring radiation or chemotherapy within the past 3 years, or concurrent therapy for MDS or AML.

Arm/Group Title	Dasatinib Dose Escalation
Arm/Group Description	Patients were started on dasatinib at a continuous oral daily dose of 100 mg per day. At 8 weeks, if the initial dose was well tolerated and patient had not achieved a partial response, the dose could be increased to 150 mg per day. All patients were followed per protocol for a total core period of 16 weeks from the first dose. Responding patients could continue dasatinib treatment for up to 48 weeks in the absence of treatment failure, disease progression, limiting toxicity or death. Patients continuing after 48 weeks will be enrolled in a separate extension study for future follow up.
Period Title: Overall Study
STARTED	18
COMPLETED	6
NOT COMPLETED	12

Baseline Characteristics

Arm/Group Title	Dasatinib Dose Escalation
Arm/Group Description	Patients were started on dasatinib at a continuous oral daily dose of 100 mg per day. At 8 weeks, if the initial dose was well tolerated and patient had not achieved a partial response, the dose could be increased to 150 mg per day. All patients were followed per protocol for a total core period of 16 weeks from the first dose. Responding patients could continue dasatinib treatment for up to 48 weeks in the absence of treatment failure, disease progression, limiting toxicity or death. Patients continuing after 48 weeks will be enrolled in a separate extension study for future follow up.
Overall Participants	18
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	73.5
Sex: Female, Male (Count of Participants)
Female	8 44.4%
Male	10 55.6%
Region of Enrollment (participants) [Number]
United States	18 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Marrow Complete Remission (CR)
Description	Complete remission (modified IWG); IWG = International MDS Working Group. Bone Marrow Response must last ≥4 weeks. Bone marrow evaluation: Bone marrow showing ≤5% myeloblasts with normal maturation of all cell lines.
Time Frame	1 Year 4 Months

Outcome Measure Data

Analysis Population Description

All Participants

Arm/Group Title	Dasatinib Dose Escalation
Arm/Group Description	Patients were started on dasatinib at a continuous oral daily dose of 100 mg per day. At 8 weeks, if the initial dose was well tolerated and patient had not achieved a partial response, the dose could be increased to 150 mg per day. All patients were followed per protocol for a total core period of 16 weeks from the first dose. Responding patients could continue dasatinib treatment for up to 48 weeks in the absence of treatment failure, disease progression, limiting toxicity or death. Patients continuing after 48 weeks will be enrolled in a separate extension study for future follow up.
Measure Participants	18
Number [participants]	3 16.7%

2. Secondary Outcome

Title	Number of Participants With Hematologic Improvement
Description	Hematologic improvement in platelets, red blood cell (RBC), neutrophils according to modified IWG Criteria; Cytogenetic response (modified IWG); Change in percentage of blasts in bone marrow and peripheral blood; Src-Tyr416 phosphorylation in medullary myeloblasts. Hematologic improvements must last ≥ 8 weeks.
Time Frame	1 Year 4 Months

Outcome Measure Data

Analysis Population Description

All Participants

Arm/Group Title	Dasatinib Dose Escalation
Arm/Group Description	Patients were started on dasatinib at a continuous oral daily dose of 100 mg per day. At 8 weeks, if the initial dose was well tolerated and patient had not achieved a partial response, the dose could be increased to 150 mg per day. All patients were followed per protocol for a total core period of 16 weeks from the first dose. Responding patients could continue dasatinib treatment for up to 48 weeks in the absence of treatment failure, disease progression, limiting toxicity or death. Patients continuing after 48 weeks will be enrolled in a separate extension study for future follow up.
Measure Participants	18
Number [participants]	0 0%

3. Secondary Outcome

Title	Number of Participants With Partial Remission (PR)
Description	Partial remission (PR) (modified IWG); IWG = International MDS Working Group. All of the CR criteria (if abnormal prior to treatment), except: Bone marrow evaluation: Blasts decreased by ≥ 50% over pretreatment but still >5%. Cellularity and morphology are not relevant.
Time Frame	1 Year 4 Months

Outcome Measure Data

Analysis Population Description

All Participants

Arm/Group Title	Dasatinib Dose Escalation
Arm/Group Description	Patients were started on dasatinib at a continuous oral daily dose of 100 mg per day. At 8 weeks, if the initial dose was well tolerated and patient had not achieved a partial response, the dose could be increased to 150 mg per day. All patients were followed per protocol for a total core period of 16 weeks from the first dose. Responding patients could continue dasatinib treatment for up to 48 weeks in the absence of treatment failure, disease progression, limiting toxicity or death. Patients continuing after 48 weeks will be enrolled in a separate extension study for future follow up.
Measure Participants	18
Number [participants]	0 0%

4. Secondary Outcome

Title	Number of Participants With Stable Disease (SD)
Time Frame	1 Year 4 Months

Outcome Measure Data

Analysis Population Description

All Participants

Arm/Group Title	Dasatinib Dose Escalation
Arm/Group Description	Patients were started on dasatinib at a continuous oral daily dose of 100 mg per day. At 8 weeks, if the initial dose was well tolerated and patient had not achieved a partial response, the dose could be increased to 150 mg per day. All patients were followed per protocol for a total core period of 16 weeks from the first dose. Responding patients could continue dasatinib treatment for up to 48 weeks in the absence of treatment failure, disease progression, limiting toxicity or death. Patients continuing after 48 weeks will be enrolled in a separate extension study for future follow up.
Measure Participants	18
Number [participants]	10 55.6%

Adverse Events

Time Frame	1 Year 4 Months
Arm/Group Title	Dasatinib Dose Escalation
Arm/Group Description	Patients were started on dasatinib at a continuous oral daily dose of 100 mg per day. At 8 weeks, if the initial dose was well tolerated and patient had not achieved a partial response, the dose could be increased to 150 mg per day. All patients were followed per protocol for a total core period of 16 weeks from the first dose. Responding patients could continue dasatinib treatment for up to 48 weeks in the absence of treatment failure, disease progression, limiting toxicity or death. Patients continuing after 48 weeks will be enrolled in a separate extension study for future follow up.
All Cause Mortality
	Dasatinib Dose Escalation
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Dasatinib Dose Escalation
	Affected / at Risk (%)	# Events
Total	9/18 (50%)
Blood and lymphatic system disorders
Blood/Bone Marrow - Grade 4	1/18 (5.6%)	1
Edema: limb - Grade 2	2/18 (11.1%)	2
Hemoglobin - Grade 3 - *Possibly related	3/18 (16.7%)	4
Hemoglobin - Grade 4 - *Possibly related	1/18 (5.6%)	1
Platelets - Grade 3 - *Possibly related	1/18 (5.6%)	1
Platelets - Grade 4 - *Possibly related	2/18 (11.1%)	2
Cardiac disorders
Cardiac general - Grade 3	1/18 (5.6%)	1
Hypertension - Grade 3	1/18 (5.6%)	1
Gastrointestinal disorders
Anorexia - Grade 3 - *Possibly related	1/18 (5.6%)	1
Dehydration - Grade 3	1/18 (5.6%)	1
Diarrhea - Grade 1	1/18 (5.6%)	1
Diarrhea - Grade 3 - *Possibly related	1/18 (5.6%)	1
Mucositis/stomatitis (oral cavity) - Grade 3	1/18 (5.6%)	2
Nausea - Grade 2	1/18 (5.6%)	1
Nausea - Grade 3 - *Possibly related	1/18 (5.6%)	1
Vomiting - Grade 1	1/18 (5.6%)	1
Vomiting - Grade 2	1/18 (5.6%)	1
Vomiting - Grade 3 - *Possibly related	1/18 (5.6%)	1
General disorders
Fatigue - Grade 3 - *Possibly related	3/18 (16.7%)	4
Fever in absence of neutropenia - Grade 2	1/18 (5.6%)	1
Hematoma - Grade 1	1/18 (5.6%)	1
Hemorrhage, GI - Lower GI NOS - Grade 3	1/18 (5.6%)	1
Hemorrhage, GI - Rectum - Grade 3 - *Possibly related	1/18 (5.6%)	1
Hemorrhage, GI - Upper GI - Grade 3 - *Possibly related	1/18 (5.6%)	1
Pain - Cardiac/heart - Grade 3	1/18 (5.6%)	1
Pain - head/headache - Grade 3	1/18 (5.6%)	1
Pain: abdomen - Grade 2	2/18 (11.1%)	2
Hepatobiliary disorders
Cholecystitis - Grade 3 - *Possibly related	1/18 (5.6%)	1
Hepatobiliary/Pancreas - Grade 1	1/18 (5.6%)	1
Infections and infestations
Febrile neutropenia - Grade 3	1/18 (5.6%)	1
Febrile neutropenia - Grade 3 - *Possibly related	1/18 (5.6%)	1
Infection - Grade 3	2/18 (11.1%)	2
Infection - Grade 3 - *Possibly related	1/18 (5.6%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils - Lung - Grade 3	1/18 (5.6%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils - lung - Grade 3 - *Possibly related	1/18 (5.6%)	1
Metabolism and nutrition disorders
Glucose, serum - low - Grade 4	1/18 (5.6%)	1
Nervous system disorders
Confusion - Grade 3	1/18 (5.6%)	1
Renal and urinary disorders
Renal failure - Grade 3	1/18 (5.6%)	1
Renal failure - Grade 3 - *Possibly related	1/18 (5.6%)	1
Renal/Genitourinary - Grade 2	1/18 (5.6%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea - Grade 2	1/18 (5.6%)	1
Dyspnea - Grade 2 - *Possibly related	1/18 (5.6%)	1
Dyspnea - Grade 3	2/18 (11.1%)	2
Dyspnea - Grade 3 - **Definitely related	1/18 (5.6%)	1
Dyspnea - Grade 3 - *Possibly related	1/18 (5.6%)	2
Pleural effusion - Grade 2 - **Definitely related	1/18 (5.6%)	1
Pleural effusion - Grade 2 - *Possibly related	1/18 (5.6%)	2
Pleural effusion - Grade 3 - *Possibly related	1/18 (5.6%)	1
Other (Not Including Serious) Adverse Events
	Dasatinib Dose Escalation
	Affected / at Risk (%)	# Events
Total	18/18 (100%)
Blood and lymphatic system disorders
Blood/Bone Marrow - *Possibly related	1/18 (5.6%)	1
Edema: limb - *3 Events possbily related	4/18 (22.2%)	4
Hemoglobin - *11 Events possibly related	6/18 (33.3%)	12
Iron overload	1/18 (5.6%)	2
Leukocytes (total WBC) - *Possibly related	2/18 (11.1%)	2
Lymphatics	2/18 (11.1%)	2
Neutrophils/granulocytes (ANC/AGC) - *Possibly related	1/18 (5.6%)	4
Platelets - *6 Events possibly related	6/18 (33.3%)	8
Cardiac disorders
Cardiac troponia I (cTnl)	1/18 (5.6%)	1
Hypertension	1/18 (5.6%)	1
Supraventricular and nodal arrhythmia - Supraventricular tachycardia	1/18 (5.6%)	1
Ear and labyrinth disorders
Auditory/Ear	1/18 (5.6%)	1
Eye disorders
Ocular/Visual - *1 Event possibly related	4/18 (22.2%)	4
Gastrointestinal disorders
Anorexia - *2 Events possibly related	3/18 (16.7%)	3
Constipation - *3 Events possibly related	4/18 (22.2%)	4
Dehydration - *Possibly related	1/18 (5.6%)	1
Diarrhea - *5 Events possibly related	8/18 (44.4%)	8
Dysgeusia - *4 Events possibly related	3/18 (16.7%)	5
Dysphagia	1/18 (5.6%)	1
Gastrointestinal - other - *3 Events possibly related	5/18 (27.8%)	9
Heartburn/dyspepsia	1/18 (5.6%)	1
Mucositis/stomatitis - Oral cavity - *Possibly related	1/18 (5.6%)	1
Nausea - *Possibly related	6/18 (33.3%)	6
Vomiting - *Possibly related	1/18 (5.6%)	2
General disorders
Dizziness	1/18 (5.6%)	1
Fatigue - *13 Events possibly related	12/18 (66.7%)	20
Fever	1/18 (5.6%)	1
Hemorrhage, GI - Oral cavity	1/18 (5.6%)	2
Hemorrhage, GI - Rectum - *1 Event possibly related	2/18 (11.1%)	2
Hemorrhage, pulmonary/upper respiratory - Lung - *Possibly related	1/18 (5.6%)	1
Insomnia	2/18 (11.1%)	2
Pain	3/18 (16.7%)	5
Pain - Abdomen - *2 Events possibly related	3/18 (16.7%)	4
Pain - Back	2/18 (11.1%)	2
Pain - Breast	1/18 (5.6%)	1
Pain - Chest wall - *1 Event possibly related	2/18 (11.1%)	3
Pain - Extremity: limb	1/18 (5.6%)	3
Pain - Head/headache - *4 Events possibly related	3/18 (16.7%)	6
Pain - Joint - *Possibly related	1/18 (5.6%)	2
Pain - Oral cavity	2/18 (11.1%)	2
Pain - Throat/pharynx/larynx - *1 Event possibly related	2/18 (11.1%)	2
Rigors/chills - *1 Event possibly related	3/18 (16.7%)	3
Sweating (diaphoresis) - *1 Event possibly related	3/18 (16.7%)	3
Weight loss - *Possibly related	3/18 (16.7%)	3
Immune system disorders
Alergic rhinitis	1/18 (5.6%)	1
Infections and infestations
Febrile neutropenia - *3 Events possibly related	4/18 (22.2%)	4
Infection - other - *2 Events possibly related	4/18 (22.2%)	6
Infection with Grade 3 or 4 neutrophils - Urinary tract - *Possibly related	1/18 (5.6%)	1
Infection with Grade 3 or 4 neutrophils - Skin - *Possibly related	1/18 (5.6%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils - Sinus - *1 Event possibly related	2/18 (11.1%)	3
Metabolism and nutrition disorders
Calcium, serum-high (hypercalcemia)	1/18 (5.6%)	1
Glucose, serum-high (hyperglycemia)	1/18 (5.6%)	3
Potassium, serum-low (hypokalemia) - *1 Event possibly related	2/18 (11.1%)	3
Musculoskeletal and connective tissue disorders
Muscle weakness - *2 Events possibly related	2/18 (11.1%)	3
Neuropathy - *Possibly related	1/18 (5.6%)	1
Psychiatric disorders
Mood alteration - Anxiety	1/18 (5.6%)	1
Renal and urinary disorders
Renal failure - *Possibly related	1/18 (5.6%)	1
Urinary frequency/urgency	1/18 (5.6%)	1
Respiratory, thoracic and mediastinal disorders
Cough - *3 Events possibly related	4/18 (22.2%)	5
Dyspnea - *6 Events possibly related	8/18 (44.4%)	14
Hypoxia - *Possibly related	1/18 (5.6%)	1
Pleural effusion - *Possibly related	2/18 (11.1%)	2
Pulmonary/Upper Respiratory - other	1/18 (5.6%)	1
Skin and subcutaneous tissue disorders
Bruising (in absence of Grade 3 or 4 thrombocytopenia) - *2 Events possibly related	6/18 (33.3%)	6
Dermatology	5/18 (27.8%)	6
Flushing - *Possibly related	1/18 (5.6%)	1
Hair loss/alopecia	1/18 (5.6%)	1
Pruritus/itching	1/18 (5.6%)	1
Rash/desquamation - *Possibly related	1/18 (5.6%)	1
Rash: acne/acneiform	2/18 (11.1%)	2
Rash: hand-foot skin reaction - *Possibly related	1/18 (5.6%)	1
Ulceration	1/18 (5.6%)	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.