An Open-Label, Phase I/II Study of Two Different Schedules of Dasatinib (Sprycel) and Decitabine (Dacogen) Used in Combination for Patients With Accelerated or Blastic Phase Chronic Myelogenous Leukemia (Protocol CA180357)

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01498445
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 32
• Location: 1
• Arms: 6
• Actual Duration (Months): 87.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if combining Sprycel (dasatinib) and Dacogen (decitabine) can help to control Chronic Myeloid Leukemia (CML). The dose level of decitabine will also be studied.

Dasatinib is designed to block the protein that is responsible for chronic myeloid leukemia.

Decitabine is designed to affect the mechanism that cells use to control the expression of certain genes, some of which are important in the progression of CML.

This is an investigational study. Dasatinib is FDA approved and commercially available for the treatment of patients with certain types of CML.

Decitabine is FDA approved for the treatment of patients with myelodysplastic syndrome.

The combination of these drugs to treat CML is investigational.

Up to 84 patients will take part in this study. All will be enrolled at MD Anderson.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: Dasatinib; Drug: Decitabine; Drug: Decitabine	Phase 1/Phase 2

Detailed Description

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study group and dose level based on when you join this study and the side effects that are seen. Your doctor will discuss this with you in more detail.

There will be up to 5 doses of dasatinib tested in Phase 1. The first 3 participants will receive a lower dose of therapy. If no major side effects are seen in these participants, the next participants will receive a higher dose. Once a dose is identified that is well-tolerated for most participants, that dose will be used for all new participants. If you are in Phase 2, you will receive a dose level tested in Phase 1.

You will receive one of 2 doses of decitabine. What dose you receive is determined by chance (like a coin toss).

Study Administration:

Each cycle is 28 days.

You will take dasatinib by mouth 1 time a day.

You will receive decitabine by vein for 10 days of each cycle. If the doctor thinks it is in your best interest, you may receive decitabine for fewer days each cycle (5 days instead of 10 days). Your doctor will decide how many doses you will take based on side effects you may have and the status of the disease.

If you have severe side effects from the study drug, the study doctor may decide to stop drug dosing until your side effects improve.

You will be asked to keep a study diary that will be reviewed at scheduled study visits. In the diary, you will record when you take the study drug.

Study Visits:

At every visit, you will be asked about any side effects you may have had and to list any drugs you may be taking.

Every week for the first 3 cycles and then every 2-4 weeks after that, blood (about 1 tablespoon) will be drawn to check your blood cell counts.

About 1 week after your first dose, you will have an ECG.

Every 1-2 weeks for the first 3 cycles and then every 4-8 weeks after that, blood (about 1 tablespoon) will be drawn to test your kidney and liver function.

Every 1-3 months, blood (about 1 tablespoon) will be drawn for genetic testing.

Before the start of Cycle 2, every 2-4 cycles after that for the first year, and then every 6 cycles after that, you will have a complete physical exam.

Before the start of Cycle 2, every 3 cycles after that during the first year, then every 4-6 cycles (as needed) you will have a bone marrow aspirate to check the status of the disease.

After Cycle 6, the number of blood draws and bone marrow collections may be changed.

Length of Study:

You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Phase I/II Study of Two Different Schedules of Dasatinib (Sprycel) and Decitabine (Dacogen) Used in Combination for Patients With Accelerated or Blastic Phase Chronic Myelogenous Leukemia (Protocol CA180357)
• Actual Study Start Date: Jun 12, 2012
• Actual Primary Completion Date: Sep 24, 2019
• Actual Study Completion Date: Sep 24, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase I - Dasatinib 100 mg + Decitabine 10 mg/m2 Less Intensive, Schedule A1 Dasatinib 100 mg daily by mouth ; Decitabine 10 mg/m^2 by vein over 1 hour daily for 10 days; 28 day cycle.	Drug: Dasatinib; Starting Dose: 100 mg by mouth once daily of a 28 day cycle.; Other Names: BMS-354825 Sprycel ; Drug: Decitabine; Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.; Other Names: Dacogen
Experimental: Phase I - Dasatinib 100 mg + Decitabine 20 mg/m2 More Intensive, Schedule A2: Dasatinib 100 mg daily by mouth ; Decitabine ose 20 mg/m^2 by vein over 1 hour daily for 10 days; 28 day cycle.	Drug: Dasatinib; Starting Dose: 100 mg by mouth once daily of a 28 day cycle.; Other Names: BMS-354825 Sprycel ; Drug: Decitabine; Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.; Other Names: Dacogen
Experimental: Phase I - Dasatinib 140 mg + Decitabine 10 mg/m2 Less Intensive, Schedule B1 Dasatinib 140 mg daily by mouth ; Decitabine 10 mg/m^2 by vein over 1 hour daily for 10 days; 28 day cycle.	Drug: Dasatinib; Starting Dose: 100 mg by mouth once daily of a 28 day cycle.; Other Names: BMS-354825 Sprycel ; Drug: Decitabine; Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.; Other Names: Dacogen
Experimental: Phase I - Dasatinib 140 mg + Decitabine 20 mg/m2 More Intensive, Schedule B2 Dasatinib 140 mg daily by mouth ; Decitabine 20 mg/m^2 by vein over 1 hour daily for 10 days; 28 day cycle.	Drug: Dasatinib; Starting Dose: 100 mg by mouth once daily of a 28 day cycle.; Other Names: BMS-354825 Sprycel ; Drug: Decitabine; Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.; Other Names: Dacogen
Experimental: Phase II - Dasatinib 140 mg + Decitabine 10 mg/m2 Less Intensive, Schedule B1 Dasatinib 140 mg daily by mouth; Decitabine e 10 mg/m^2 by vein over 1 hour daily for 10 days; 28 day cycle.	Drug: Dasatinib; Starting Dose: 100 mg by mouth once daily of a 28 day cycle.; Other Names: BMS-354825 Sprycel ; Drug: Decitabine; Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.; Other Names: Dacogen
Experimental: Phase II - Dasatinib 140 mg + Decitabine 20 mg/m2 More Intensive, Schedule B2 Dasatinib140 mg daily by mouth; Decitabine 20 mg/m^2 by vein over 1 hour daily for 10 days; 28 day cycle.	Drug: Dasatinib; Starting Dose: 100 mg by mouth once daily of a 28 day cycle.; Other Names: BMS-354825 Sprycel ; Drug: Decitabine; Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.; Other Names: Dacogen

Outcome Measures

Primary Outcome Measures

1. Ph I Study: Maximum Tolerated Dose (MTD) Dasatinib [End of first 28-day cycle]

   Maximum tolerated dose (MTD) defined as highest dose at which 0 of 3 or </= 1/6 participant experience a first cycle dose limiting toxicity (DLT).

Secondary Outcome Measures

1. Number of Participants With Hematologic Responses During First 3 Months of Treatment [3 months]

   Number of participants with hematologic response (HR) to therapy during first 3 months of combination dasatinib and decitabine therapy, where HR defined as any hematologic response observed during the first 3 months of treatment. Overall Hematologic Response (OHR) is defined as complete hematologic response (CHR), no evidence of leukemia (NEL) or minor hematologic response (MiHR)

2. Overall Survival [Up to seven years]

   Overall Survival will be measured from the date treatment is started to the date of death or last follow-up.

3. Duration of Response [up to seven years]

   Duration of Response will be measured from the date the given response is achieved to the date the response is first known to be lost

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Patients age 18 years of age or older with CML-AP, CML-BP or Philadelphia chromosome-positive acute myeloid leukemia defined as follows: CML-AP is defined by the presence of 15-29% blasts in peripheral blood (PB) or bone marrow (BM), >/= 20% basophils in PB or BM, >/= 30% blasts plus promyelocytes (with blasts <30%) in PB or BM, <100 x10(9)/L platelets unrelated to therapy, or by clonal cytogenetics evolution (i.e., the presence of cytogenetic abnormalities other than the Philadelphia chromosome); CML-BP is defined by the presence of >/= 30% blasts in the bone marrow and/or peripheral blood or the presence of extramedullary disease.

2. Patients are eligible whether they have received or not prior TKI therapy. For the phase I portion of the study, patients who had received prior therapy with dasatinib should have been able to tolerate the dose equivalent to the starting dose of dasatinib in the dose level at which the patient is being entered. Patients who previously received dasatinib but never at the dose being proposed are eligible provided they tolerated the maximum dose they were prescribed with no grade 3-4 toxicity not responding to optimal management.

3. Eastern Cooperative Oncology Group (ECOG) performance status 0-3.

4. Men and women of childbearing potential should practice 2 methods of contraception; 1 method must be highly effective and a second method must be either highly effective or less effective. Men and women of childbearing potential are defined as: a male that has not been surgically sterilized or a female that has not been amenorrheic for at least 12 consecutive months or that has not been surgically sterilized. Patients must use birth control during the study and for 3 months after the last dose of study drug if they are sexually active.

5. Women of childbearing potential must have a pregnancy test at screening.

6. Signed informed consent.

7. Patients must have been off all prior therapy for CML for 2 weeks prior to start of study therapy and recovered from the toxic effects of that therapy. Exceptions to these are hydroxyurea and Tyrosine kinase inhibitor (TKIs) (including but not limited to imatinib, nilotinib, and bosutinib) which should be discontinued >/= 24 hrs prior to the start of therapy. Patients who are receiving dasatinib prior to enrollment do not have to discontinue this agent prior to start of study therapy.

8. Adequate organ function: Serum creatinine </= 2.0 mg/dl or creatinine clearance >/=60 mL/min; Total bilirubin </= 1.5 x upper limit of normal (ULN) (unless considered due to Gilbert's syndrome or hemolysis); Alanine aminotransferase (ALT) </= 3 x ULN unless considered due to leukemic involvement.

Exclusion Criteria:

1. New York Heart Association (NYHA) cardiac class 3-4 heart disease.

2. Cardiac disease including: Uncontrolled angina within 3 months. Diagnosed or suspected congenital long QT syndrome; Any history of clinically significant ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, or Torsades de pointes); Prolonged QTc interval on pre-entry electrocardiogram (> 470 msec) on the Fridericia's correction; Uncontrolled hypertension (defined for this protocol as sustained systolic BP >/=150 and diastolic >/=100); Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes.

3. Serious uncontrolled medical disorder or uncontrolled active systemic infection or current unstable or decompensated respiratory or cardiac conditions which makes it undesirable or unsafe for the patient to participate in the study.

4. Patients with known, clinically significant pericardial or pleural effusion.

5. History of significant bleeding disorder unrelated to cancer, including diagnosed congenital bleeding disorders (e.g., von Willebrand's disease), or diagnosed acquired bleeding disorders within one year (e.g., acquired anti-factor VIII antibodies).

6. Subject is receiving potent inhibitors of CYP3A4; for such medications, a wash-out period of >/= 7 days is required prior to starting dasatinib unless discontinuation or substitution of such an inhibitor is not in the best interest of the patient as determined by the investigator. These include the following medications: itraconazole, ketoconazole, miconazole, voriconazole; amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir; ciprofloxacin, clarithromycin, diclofenac, doxycycline, enoxacin, isoniazid, ketamine, nefazodone, nicardipine, propofol, quinidine, telithromycin. In instances where use of these agents is felt to be required for the best management of the patients, inclusion of such a patients should be discussed with PI and the rationale documented.

7. Females who are pregnant or are currently breastfeeding.

8. Patients that are eligible (including having available donor) and willing to receive an allogeneic stem cell transplant within 4 weeks.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Bristol-Myers Squibb

Investigators

• Principal Investigator: Jorge Cortes, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 15, 2016

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01498445
• Other Study ID Numbers: 2011-0333; CA180357; NCI-2012-00014
• First Posted: Dec 23, 2011
• Last Update Posted: Oct 22, 2020
• Last Verified: Sep 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by M.D. Anderson Cancer Center: Leukemia; Chronic myelogenous leukemia; Chronic myeloid leukemia; CML; Accelerated phase; Blastic phase; Dasatinib; BMS-354825; Sprycel; Decitabine; Dacogen
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Blast Crisis; Decitabine; Dasatinib

Study Results

Participant Flow

Recruitment Details	Recruitment Period: June 2012 to April 2018

Arm/Group Title	Phase I Schedule A1	Phase I Schedule A2	Phase I Schedule B1	Phase I Schedule B2	Phase II B1	Phase II B2
Arm/Group Description	Dasatinib 100mg + Decitabine 10 mg/m2	Dasatinib 100 mg + Decitabine 20 mg/m2	Dasatinib 140 mg + Decitabine 10 mg/m2	Dasatinib 140 mg+ Decitabine 20 mg/m2	Dasatinib 140 mg + Decitabine 10 mg/m2	Dasatinib 140 mg + Decitabine 20 mg/m2
Period Title: Overall Study
STARTED	4	3	8	8	4	5
COMPLETED	4	3	7	6	3	4
NOT COMPLETED	0	0	1	2	1	1

Baseline Characteristics

Arm/Group Title	Phase I - Dasatinib 100 mg + Decitabine 10 mg/m2	Phase I - Dasatinib 100 mg + Decitabine 20 mg/m2	Phase I - Dasatinib 140 mg + Decitabine 10 mg/m2	Phase I - Dasatinib 140 mg + Decitabine 20 mg/m2	Phase II - Dasatinib 140 mg + Decitabine 10 mg/m2	Phase II - Dasatinib 140 mg + Decitabine 20 mg/m2	Total
Arm/Group Description	Less Intensive, Schedule A1 Dasatinib starting dose of 100 mg by mouth daily; Decitabine starting dose 10 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.	More Intensive, Schedule A2: Dasatinib starting dose 100 mg by mouth daily; Decitabine starting dose 20 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.	Less Intensive, Schedule B1 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 10 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.	More Intensive, Schedule B2 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 20 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.	Less Intensive, Schedule B1 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 10 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.	More Intensive, Schedule B2 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 20 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.	Total of all reporting groups
Overall Participants	4	3	8	8	4	5	32
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	4 100%	3 100%	7 87.5%	7 87.5%	4 100%	2 40%	27 84.4%
>=65 years	0 0%	0 0%	1 12.5%	1 12.5%	0 0%	3 60%	5 15.6%
Sex: Female, Male (Count of Participants)
Female	1 25%	3 100%	3 37.5%	2 25%	2 50%	1 20%	12 37.5%
Male	3 75%	0 0%	5 62.5%	6 75%	2 50%	4 80%	20 62.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	1 12.5%	0 0%	0 0%	1 3.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 25%	0 0%	2 25%	3 37.5%	1 25%	0 0%	7 21.9%
White	3 75%	3 100%	6 75%	4 50%	1 25%	5 100%	22 68.8%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	2 50%	0 0%	2 6.3%
Region of Enrollment (participants) [Number]
United States	4 100%	3 100%	8 100%	8 100%	4 100%	5 100%	32 100%

Outcome Measures

1. Primary Outcome

Title	Ph I Study: Maximum Tolerated Dose (MTD) Dasatinib
Description	Maximum tolerated dose (MTD) defined as highest dose at which 0 of 3 or </= 1/6 participant experience a first cycle dose limiting toxicity (DLT).
Time Frame	End of first 28-day cycle

Outcome Measure Data

Analysis Population Description

Participants who did not complete 2 cycles of therapy were ineligible for response. Maximum Tolerate Dose (MTD) was not done for the Phase II portion of the study, therefore zero participants in the Phase II arms were analyzed for this outcome.

Arm/Group Title	Phase I - Dasatinib 100 mg + Decitabine 10 mg/m2	Phase I - Dasatinib 100 mg + Decitabine 20 mg/m2	Phase I - Dasatinib 140 mg + Decitabine 10 mg/m2	Phase I - Dasatinib 140 mg + Decitabine 20 mg/m2	Phase II - Dasatinib 140 mg + Decitabine 10 mg/m2	Phase II - Dasatinib 140 mg + Decitabine 20 mg/m2
Arm/Group Description	Less Intensive, Schedule A1 Dasatinib starting dose of 100 mg by mouth daily; Decitabine starting dose 10 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.	More Intensive, Schedule A2: Dasatinib starting dose 100 mg by mouth daily; Decitabine starting dose 20 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.	Less Intensive, Schedule B1 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 10 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.	More Intensive, Schedule B2 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 20 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.	Less Intensive, Schedule B1 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 10 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.	More Intensive, Schedule B2 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 20 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.
Measure Participants	4	3	7	6	0	0
Number [Milligrams]	NA	NA	140	140

2. Secondary Outcome

Title	Number of Participants With Hematologic Responses During First 3 Months of Treatment
Description	Number of participants with hematologic response (HR) to therapy during first 3 months of combination dasatinib and decitabine therapy, where HR defined as any hematologic response observed during the first 3 months of treatment. Overall Hematologic Response (OHR) is defined as complete hematologic response (CHR), no evidence of leukemia (NEL) or minor hematologic response (MiHR)
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

1 participant in Ph 1 Dasatinib 140 mg + Decitabine 10 mg/m^2 arm was not evaluable for response. 2 participants in the Ph 1 Dasatinib 140 mg + Decitabine 20 mg/m^2 arm were not evaluable for response. 1 participant in Ph II Dasatinib 140 mg + Decitabine 10mg/m^2 and 1 participant in Ph II Dasatinib 140 mg + Decitabine 20mg/m^2 failed screening.

Arm/Group Title	Phase I - Dasatinib 100 mg + Decitabine 10 mg/m2	Phase I - Dasatinib 100 mg + Decitabine 20 mg/m2	Phase I - Dasatinib 140 mg + Decitabine 10 mg/m2	Phase I - Dasatinib 140 mg + Decitabine 20 mg/m2	Phase II - Dasatinib 140 mg + Decitabine 10 mg/m2	Phase II - Dasatinib 140 mg + Decitabine 20 mg/m2
Arm/Group Description	Less Intensive, Schedule A1 Dasatinib starting dose of 100 mg by mouth daily; Decitabine starting dose 10 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.	More Intensive, Schedule A2: Dasatinib starting dose 100 mg by mouth daily; Decitabine starting dose 20 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.	Less Intensive, Schedule B1 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 10 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.	More Intensive, Schedule B2 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 20 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.	Less Intensive, Schedule B1 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 10 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.	More Intensive, Schedule B2 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 20 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.
Measure Participants	4	3	7	6	3	4
Count of Participants [Participants]	3 75%	1 33.3%	5 62.5%	4 50%	3 75%	3 60%

3. Secondary Outcome

Title	Overall Survival
Description	Overall Survival will be measured from the date treatment is started to the date of death or last follow-up.
Time Frame	Up to seven years

Outcome Measure Data

Analysis Population Description

1 participant in Ph 1 Dasatinib 140 mg + Decitabine 10 mg/m^2 arm was not evaluable for response. Two participants in the Ph 1 Dasatinib 140 mg + Decitabine 20 mg/m^2 arm were not evaluable for response.

Arm/Group Title	Phase I - Dasatinib 100 mg + Decitabine 10 mg/m2	Phase I - Dasatinib 100 mg + Decitabine 20 mg/m2	Phase I - Dasatinib 140 mg + Decitabine 10 mg/m2	Phase I - Dasatinib 140 mg + Decitabine 20 mg/m2	Phase II - Dasatinib 140 mg + Decitabine 10 mg/m2	Phase II - Dasatinib 140 mg + Decitabine 20 mg/m2
Arm/Group Description	Less Intensive, Schedule A1 Dasatinib starting dose of 100 mg by mouth daily; Decitabine starting dose 10 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.	More Intensive, Schedule A2: Dasatinib starting dose 100 mg by mouth daily; Decitabine starting dose 20 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.	Less Intensive, Schedule B1 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 10 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.	More Intensive, Schedule B2 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 20 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.	Less Intensive, Schedule B1 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 10 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.	More Intensive, Schedule B2 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 20 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.
Measure Participants	4	3	7	6	3	4
Median (Full Range) [Months]	12.0	7.0	57.8	58.2	62.0	37.5

4. Secondary Outcome

Title	Duration of Response
Description	Duration of Response will be measured from the date the given response is achieved to the date the response is first known to be lost
Time Frame	up to seven years

Outcome Measure Data

Analysis Population Description

1 participant in Ph 1 Dasatinib 140 mg + Decitabine 10 mg/m^2 arm was not evaluable for response. Two participants in the Ph 1 Dasatinib 140 mg + Decitabine 20 mg/m^2 arm were not evaluable for response.

Arm/Group Title	Phase I - Dasatinib 100 mg + Decitabine 10 mg/m2	Phase I - Dasatinib 100 mg + Decitabine 20 mg/m2	Phase I - Dasatinib 140 mg + Decitabine 10 mg/m2	Phase I - Dasatinib 140 mg + Decitabine 20 mg/m2	Phase II - Dasatinib 140 mg + Decitabine 10 mg/m2	Phase II - Dasatinib 140 mg + Decitabine 20 mg/m2
Arm/Group Description	Less Intensive, Schedule A1 Dasatinib starting dose of 100 mg by mouth daily; Decitabine starting dose 10 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.	More Intensive, Schedule A2: Dasatinib starting dose 100 mg by mouth daily; Decitabine starting dose 20 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.	Less Intensive, Schedule B1 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 10 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.	More Intensive, Schedule B2 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 20 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.	Less Intensive, Schedule B1 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 10 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.	More Intensive, Schedule B2 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 20 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.
Measure Participants	4	3	7	6	3	4
Median (Full Range) [Months]	36.8	82	57.8	58	61	37

Adverse Events

Time Frame	Up to seven years
Arm/Group Title	Phase I - Dasatinib 100 mg + Decitabine 10 mg/m2		Phase I - Dasatinib 100 mg + Decitabine 20 mg/m2		Phase I - Dasatinib 140 mg + Decitabine 10 mg/m2		Phase I - Dasatinib 140 mg + Decitabine 20 mg/m2		Phase II - Dasatinib 140 mg + Decitabine 10 mg/m2		Phase II - Dasatinib 140 mg + Decitabine 20 mg/m2
Arm/Group Description	Less Intensive, Schedule A1 Dasatinib starting dose of 100 mg by mouth daily; Decitabine starting dose 10 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.		More Intensive, Schedule A2: Dasatinib starting dose 100 mg by mouth daily; Decitabine starting dose 20 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.		Less Intensive, Schedule B1 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 10 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.		More Intensive, Schedule B2 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 20 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.		Less Intensive, Schedule B1 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 10 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (less intensive group) Schedule A: 10 mg/m2 by vein daily for 10 days of a 28 day cycle.		More Intensive, Schedule B2 Dasatinib starting dose of 140 mg by mouth daily; Decitabine starting dose 20 mg/m2 by vein over 1 hour daily for 10 days; 28 day cycle. Dasatinib: Starting Dose: 100 mg by mouth once daily of a 28 day cycle. Decitabine: Starting Dose (more intensive group) Schedule B: 20 mg/m2 by vein daily for 10 days of a 28 day cycle.
All Cause Mortality
	Phase I - Dasatinib 100 mg + Decitabine 10 mg/m2		Phase I - Dasatinib 100 mg + Decitabine 20 mg/m2		Phase I - Dasatinib 140 mg + Decitabine 10 mg/m2		Phase I - Dasatinib 140 mg + Decitabine 20 mg/m2		Phase II - Dasatinib 140 mg + Decitabine 10 mg/m2		Phase II - Dasatinib 140 mg + Decitabine 20 mg/m2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		1/3 (33.3%)		2/8 (25%)		0/8 (0%)		0/4 (0%)		0/5 (0%)
Serious Adverse Events
	Phase I - Dasatinib 100 mg + Decitabine 10 mg/m2		Phase I - Dasatinib 100 mg + Decitabine 20 mg/m2		Phase I - Dasatinib 140 mg + Decitabine 10 mg/m2		Phase I - Dasatinib 140 mg + Decitabine 20 mg/m2		Phase II - Dasatinib 140 mg + Decitabine 10 mg/m2		Phase II - Dasatinib 140 mg + Decitabine 20 mg/m2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/4 (75%)		3/3 (100%)		7/8 (87.5%)		6/8 (75%)		3/4 (75%)		4/5 (80%)
Blood and lymphatic system disorders
Anemia	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	2	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Blood and Lymphatic System Disorders	0/4 (0%)	0	1/3 (33.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Neutropenic Fever	1/4 (25%)	1	2/3 (66.7%)	2	1/8 (12.5%)	1	1/8 (12.5%)	1	0/4 (0%)	0	1/5 (20%)	2
Leukocytosis	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	1	1/8 (12.5%)	1	0/4 (0%)	0	0/5 (0%)	0
Cardiac disorders
Cardiac Arrest	0/4 (0%)	0	0/3 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/4 (0%)	0	0/5 (0%)	0
Chest Pain	0/4 (0%)	0	0/3 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/4 (0%)	0	0/5 (0%)	0
Heart Failure	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Myocardial Infarction	0/4 (0%)	0	0/3 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/4 (0%)	0	0/5 (0%)	0
Gastrointestinal disorders
Diarrhea	0/4 (0%)	0	0/3 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/4 (0%)	0	1/5 (20%)	1
Gastric Hemorrhage	0/4 (0%)	0	1/3 (33.3%)	1	0/8 (0%)	0	1/8 (12.5%)	1	0/4 (0%)	0	0/5 (0%)	0
Pancreatitis	0/4 (0%)	0	0/3 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/4 (0%)	0	0/5 (0%)	0
Rectal Pain	0/4 (0%)	0	0/3 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/4 (0%)	0	0/5 (0%)	0
General disorders
Abdominal Pain	0/4 (0%)	0	0/3 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	2	0/4 (0%)	0	0/5 (0%)	0
Fever	1/4 (25%)	1	0/3 (0%)	0	3/8 (37.5%)	3	1/8 (12.5%)	1	1/4 (25%)	1	0/5 (0%)	0
General Administration Site	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Infections and infestations
Infection	0/4 (0%)	0	0/3 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/4 (25%)	1	0/5 (0%)	0
Lung Infection	2/4 (50%)	2	1/3 (33.3%)	1	1/8 (12.5%)	1	1/8 (12.5%)	2	2/4 (50%)	6	2/5 (40%)	2
Sepsis	0/4 (0%)	0	1/3 (33.3%)	1	1/8 (12.5%)	1	0/8 (0%)	0	1/4 (25%)	1	0/5 (0%)	0
Metabolism and nutrition disorders
Tumor Lysis Syndrome	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Musculoskeletal and connective tissue disorders
Bone Pain	0/4 (0%)	0	0/3 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/4 (25%)	1	0/5 (0%)	0
Nervous system disorders
Headache	0/4 (0%)	0	0/3 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/4 (0%)	0	0/5 (0%)	0
Psychiatric disorders
Confusion	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Renal and urinary disorders
Acute Kidney Injury	1/4 (25%)	1	0/3 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Renal and Urinary Disorders	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome	1/4 (25%)	1	0/3 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/4 (0%)	0	1/5 (20%)	1
Pleural Effusion	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Pneumothorax	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Respiratory Failure	0/4 (0%)	0	0/3 (0%)	0	0/8 (0%)	0	2/8 (25%)	2	0/4 (0%)	0	0/5 (0%)	0
Respiratory Thoracic and Mediastinal Disorders Other	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Skin and subcutaneous tissue disorders
Periorbital Edema	0/4 (0%)	0	0/3 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/4 (0%)	0	1/5 (20%)	1
Rash	0/4 (0%)	0	0/3 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/4 (0%)	0	1/5 (20%)	1
Vascular disorders
Hypertension	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Hypotension	0/4 (0%)	0	0/3 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/4 (0%)	0	1/5 (20%)	1
Thromboembolic Event	0/4 (0%)	0	0/3 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	1/4 (25%)	1	0/5 (0%)	0
Other (Not Including Serious) Adverse Events
	Phase I - Dasatinib 100 mg + Decitabine 10 mg/m2		Phase I - Dasatinib 100 mg + Decitabine 20 mg/m2		Phase I - Dasatinib 140 mg + Decitabine 10 mg/m2		Phase I - Dasatinib 140 mg + Decitabine 20 mg/m2		Phase II - Dasatinib 140 mg + Decitabine 10 mg/m2		Phase II - Dasatinib 140 mg + Decitabine 20 mg/m2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		3/3 (100%)		7/8 (87.5%)		8/8 (100%)		3/4 (75%)		4/5 (80%)
Blood and lymphatic system disorders
Neutropenic Fever	0/4 (0%)	0	0/3 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/4 (25%)	1	0/5 (0%)	0
Cardiac disorders
Chest Pain	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Pericardial Effusion	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Gastrointestinal disorders
Constipation	0/4 (0%)	0	0/3 (0%)	0	0/8 (0%)	0	4/8 (50%)	5	0/4 (0%)	0	1/5 (20%)	1
Diarrhea	1/4 (25%)	1	3/3 (100%)	3	3/8 (37.5%)	3	2/8 (25%)	2	0/4 (0%)	0	0/5 (0%)	0
Mucositis	1/4 (25%)	1	0/3 (0%)	0	1/8 (12.5%)	1	2/8 (25%)	2	1/4 (25%)	1	1/5 (20%)	1
Nausea	3/4 (75%)	3	1/3 (33.3%)	1	4/8 (50%)	5	3/8 (37.5%)	4	2/4 (50%)	2	0/5 (0%)	0
Vomiting	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	1	2/8 (25%)	2	1/4 (25%)	1	0/5 (0%)	0
General disorders
Edema	1/4 (25%)	1	1/3 (33.3%)	2	3/8 (37.5%)	3	2/8 (25%)	3	2/4 (50%)	2	0/5 (0%)	0
Fatigue	0/4 (0%)	0	0/3 (0%)	0	0/8 (0%)	0	4/8 (50%)	5	0/4 (0%)	0	0/5 (0%)	0
Fever	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	1	3/8 (37.5%)	3	0/4 (0%)	0	1/5 (20%)	1
Pain	3/4 (75%)	9	0/3 (0%)	0	4/8 (50%)	4	3/8 (37.5%)	8	1/4 (25%)	3	2/5 (40%)	6
Hemorrhage	0/4 (0%)	0	1/3 (33.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Infections and infestations
Infection	3/4 (75%)	3	1/3 (33.3%)	1	1/8 (12.5%)	1	5/8 (62.5%)	6	2/4 (50%)	3	3/5 (60%)	4
Investigations
Elevated Amylase	1/4 (25%)	1	0/3 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Elevated Lipase	1/4 (25%)	1	0/3 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Hyperbilirubinemia	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/4 (0%)	0	1/5 (20%)	3
Neutropenia	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	2	4/8 (50%)	5	1/4 (25%)	3	2/5 (40%)	2
Thrombocytopenia	1/4 (25%)	1	0/3 (0%)	0	0/8 (0%)	0	2/8 (25%)	5	1/4 (25%)	2	2/5 (40%)	3
Weight Gain	1/4 (25%)	1	1/3 (33.3%)	1	0/8 (0%)	0	1/8 (12.5%)	1	0/4 (0%)	0	0/5 (0%)	0
Metabolism and nutrition disorders
Hypercalcemia	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Hyperkalemia	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Hypokalemia	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/4 (0%)	0	2/5 (40%)	2
Nervous system disorders
Headache	0/4 (0%)	0	1/3 (33.3%)	1	1/8 (12.5%)	1	5/8 (62.5%)	6	2/4 (50%)	2	1/5 (20%)	1
Peripheral Neuropathy	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	1	1/8 (12.5%)	1	0/4 (0%)	0	0/5 (0%)	0
Psychiatric disorders
Anxiety	0/4 (0%)	0	1/3 (33.3%)	1	3/8 (37.5%)	3	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Renal and urinary disorders
Acute Kidney Injury	0/4 (0%)	0	0/3 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	2/4 (50%)	2	0/3 (0%)	0	1/8 (12.5%)	1	1/8 (12.5%)	1	0/4 (0%)	0	1/5 (20%)	1
Dyspnea	2/4 (50%)	2	1/3 (33.3%)	1	0/8 (0%)	0	1/8 (12.5%)	1	0/4 (0%)	0	0/5 (0%)	0
Pleural Effusion	0/4 (0%)	0	0/3 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/4 (25%)	1	1/5 (20%)	1
Skin and subcutaneous tissue disorders
Rash	1/4 (25%)	1	1/3 (33.3%)	1	1/8 (12.5%)	1	4/8 (50%)	6	1/4 (25%)	1	2/5 (40%)	3
Vascular disorders
Hypotension	1/4 (25%)	1	0/3 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0
Hot Flashes	2/4 (50%)	2	0/3 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/4 (0%)	0	0/5 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.