Pacritinib Combined With Decitabine or Cytarabine in Older Patients With AML

• Sponsor: Weill Medical College of Cornell University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02532010
• Collaborator: (none)
• Enrollment: 13
• Location: 1
• Arms: 2
• Actual Duration (Months): 28.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to see if a medicine called pacritinib is both safe and effective as a study intervention for patients with AML in combination with either decitabine or cytarabine. Pacritinib is an experimental drug that is being studied to treat acute myeloid leukemia (AML). Decitabine and cytarabine are both FDA approved drugs that are used in treatment of AML. Pacritinib is being tested in clinical trials and has not been submitted to the U.S. Food and Drug Administration (FDA) for approval for any indications. Pacritinib is a drug that is designed to slow down the growth of leukemic cells.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia (AML)	Drug: Pacritinib; Drug: Decitabine; Drug: Cytarabine	Phase 2

Detailed Description

This is a single-center, open label, two-arm phase II study of clinical activity of pacritinib in older patients newly diagnosed with AML combined with either decitabine or cytarabine. In this study, approximately 61 patients will be enrolled at the Weill Cornell Medical College. Arm A consists of pacritinib and decitabine and will enroll 31 subjects, and Arm B consists of pacritinib and cytarabine and will enroll 30 subjects. Arm A and B will enroll sequentially. The dose of pacritinib will be 200mg twice a day continuously.

Arm A: Each cycle: Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily.

Arm B: Each cycle: Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily.

Treatment may be given on an outpatient basis if hospitalization is not otherwise required. Every effort should be made to give decitabine or cytarabine consecutively for 10 days; however if interruption is needed, discussion will be held with the medical monitor and the investigator.

The first day of a cycle will be defined as the day on which decitabine or cytarabine is started. First treatment will take place on Cycle 1, day 1. Hydroxyurea may be used at the investigator's discretion for the first 28 days on Cycle 1 to maintain white blood cell count (WBC) <30,000/µl. Bone marrow biopsy and aspiration will be performed between days 22-56 of each cycle and the subsequent treatment cycle will be started between days 22-56, at the investigator's discretion. Ideally, cycles will be administered at 28-day intervals, but treatment delays of decitabine or cytarabine up to 56 days will be permitted to allow resolution of non-hematologic and non-disease-related hematologic toxicities. Granulocyte-stimulating cytokine support will be permitted at the investigator's discretion in the event of neutropenic fever/sepsis as per American Society of Clinical Oncology (ASCO) guidelines.16 Bone marrow aspiration and biopsy will be performed within 5 days of peripheral blood count recovery to an absolute neutrophil count (ANC) ≥ 1000/µL and platelets ≥ 100,000/µL without transfusions, or day 28 whichever comes first. If the peripheral blood absolute blast count is ≥ 5000/µL on day 21 of the first cycle, the second cycle may be administered immediately after bone marrow aspiration and biopsy.

Each arm will enroll in a Simon's two-stage design as described in Section 8. In Arm A, 16 subjects will initially be entered into the study, and if 6 or fewer respond, then Arm A will be terminated early and study will proceed to Arm B. In Arm B, 15 subjects will initially be entered into the study, and if 2 or fewer respond, the study will be terminated early.

Duration of study therapy Patients will receive a minimum of 4 cycles of treatment unless there is evidence of unacceptable regimen-related toxicity or unequivocal disease progression for which the investigator is specifically recommending alternative therapy. Pacritinib will continue throughout the study.

Arm A:

Patients who achieve Complete Remission (CR), Complete Remission with incomplete platelet recovery (CRp), or complete remission with incomplete blood count recovery (CRi) will receive subsequent cycles of decitabine on a monthly basis with decitabine 20mg/m2 IV daily for 5 days with pacritinib. Patients who do not achieve complete remission, but who are responding to treatment (partial response, hematologic response, or clinical benefit as determined by the investigator) will receive four 10-day cycles of decitabine with pacritinib as indicated in the study design, followed by monthly maintenance cycles of decitabine 20mg/m2 IV daily for 5 days + daily pacritinib. The maintenance cycles will continue indefinitely until relapse or toxicity. Patients may be taken off study for allogeneic stem cell transplantation at the discretion of the investigator.

Arm B:

Patients will continue cytarabine 20mg subcutaneous twice daily for 10 days combined with pacritinib for up to 4 cycles to achieve CR, CRp, or CRi. Those patients who achieve CR, CRp, or CRi after 4 cycles may continue to receive monthly maintenance of cytarabine 20mg subcutaneous twice daily for 10 days with pacritinib. The maintenance cycles will continue indefinitely until relapse or toxicity. Patients may be taken off study for allogeneic stem cell transplantation at the discretion of the investigator.

Screening (Study Day -14 to Day 1) Initiate and complete screening activities within 14 days before Cycle 1, Day 1 treatment.

Treatment (Cycle 1, Day 1 through End-of-Treatment Visit) This period begins on the day the patient first receives treatment and ends at the End-of-Treatment Visit.

Follow-up After completion of the End-of-Treatment Visit, all patients are followed up for 30 days and followed every three months for survival and disease status.

Clinical Study Endpoints The Primary objective of the study is to evaluate the safety and efficacy of pacritinib combined with decitabine or cytarabine in newly diagnosed older (≥65 years old) patients with AML. The primary endpoint of this study will be complete remission according to the International Working Group (IWG) criteria.

The following secondary endpoints will be evaluated:

• Overall Survival (OS)

• Overall remission (OS) rate, defined as CR + CRp + Cri + Partial Remission (PR) based on IWG response criteria

• Relapse-free Survival (RFS)

• Event-free Survival (EFS)

• Time to Complete Response (TTCR)

• Remission Duration

DISCUSSION OF STUDY DESIGN

Prognosis for older patients with AML is poor, with median survival of only 9-12 months. Older patients are often not candidates for intensive chemotherapy or allogeneic stem cell transplantation. Decitabine and low-dose cytarabine are frequently used for upfront treatment of older AML patients, however CR rates are 40-50% with decitabine and 18% with cytarabine. Pacritinib is a potent tyrosine kinase inhibitor of FLT3 and Janus Kinase 3 (JAK3) tyrosine kinases. The objective of the proposed clinical trial is to evaluate the efficacy, safety, and feasibility of pacritinib combined with decitabine or cytarabine in newly diagnosed older AML patients. The primary endpoint will be increase in complete remission.

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Induction Therapy With Pacritinib Combined With Decitabine or Cytarabine in Older Patients With Acute Myeloid Leukemia (AML)
• Actual Study Start Date: Jun 15, 2015
• Actual Primary Completion Date: Feb 9, 2016
• Actual Study Completion Date: Oct 24, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm A: Pacritinib and Decitabine Arm A: Each cycle: Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily.	Drug: Pacritinib; Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nanomolar (nM)and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit Janus kinase 1 (JAK1).; Other Names: SB1518 ; Drug: Decitabine; Commercial drug: For each cycle Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily.; Other Names: Dacogen
Active Comparator: Arm B: Pacritinib and Cytarabine Arm B: Each cycle: Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily.	Drug: Pacritinib; Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nanomolar (nM)and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit Janus kinase 1 (JAK1).; Other Names: SB1518 ; Drug: Cytarabine; Commercial drug: For each cycle Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily.; Other Names: Cytosar-U, Tarabine PFS, Cytosar

Outcome Measures

Primary Outcome Measures

1. Complete Remission Rate [6 months]

   Complete remission rate is defined as number of subjects with complete remission according to the IWG criteria, which is defined by presence of <5 percent of blasts in the bone marrow, absence of blasts with Auer rods, absence of extramedullary disease, absolute neutrophil count >1.0 x 109/L (1000/µL); platelet count >100 x 109/L (100,000/µL); independence of red cell transfusions.

Secondary Outcome Measures

1. Overall Survival [2 years]

   Survival following treatment to the date of death

2. Overall Remission Rate [6 months]

   Overall remission rate is defined as number of subjects with complete remission (CR), Complete Remission with incomplete platelet recovery (CRp), Complete Remission with Incomplete Blood Count Recovery (CRi), Partial Remission (PR) according to the IWG criteria. CRi is defined as All CR criteria except for residual neutropenia (<1.0 x 109/L (1000/µL)) or thrombocytopenia (<100 x 109/L (100,000/µL)), PR is defined as relevant in the setting of phase I and II clinical trials only; all hematologic criteria of CR; decrease of bone marrow blast percentage to 5 to 25 percent; and decrease of pretreatment bone marrow blast percentage by at least 50 percent.

3. Relapse-free Survival [From date of complete remission until either AML relapse or death from any cause, whichever came first, assessed throughout the study period up to 2 years]

   Time from complete remission documentation to either AML relapse or death from any cause.

4. Event-free Survival [Time from entry on study until time at which there is treatment failure, AML relapse, or death from any cause, assessed throughout the study period up to 2 years]

   Time from entry on study until time at which there is treatment failure, AML relapse, or death from any cause

5. Time to Complete Response [From entry on study until complete remission, assessed throughout the study period up to 2 years]

   Time from entry on study until documentation of complete remission (CR)

6. Remission Duration [time from complete remission to AML relapse, assessed throughout the study period up to 2 years.]

   Time from CR documentation to AML relapse

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patient has unequivocal pathologic diagnosis of AML (≥ 20% blasts in the bone marrow based on World Health Organization (WHO) criteria), excluding acute promyelocytic leukemia t(15;17)(q22;q12); Promyelocytic leukemia gene (PML)- retinoic acid receptor alpha (RARA)

2. Age ≥ 65 years old

3. No prior treatment for AML except:

• Emergency leukapheresis

• Emergency treatment for hyperleukocytosis with hydroxyurea

• Cranial radiotherapy (RT) for Central Nervous System (CNS) leukostasis (one dose only)

• Growth factor/cytokine support

1. AML patients with therapy-related myeloid neoplasms are eligible if they have not received radiation therapy or chemotherapy (not including hormonal therapy) for their primary malignancy or disorder for ≥ 6 months. Hydroxyurea may be used at the investigator's discretion up to the first 28 days on Cycle 1 to maintain WBC <30,000/µl.

2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

3. Subjects must have adequate hepatic and renal function

4. Female subject of child-bearing potential and male subjects with female partners of reproductive potential must use acceptable contraceptive methods

5. Able to understand and to provide written informed consent

6. Able to comply with all study procedures during the study including all visits and tests

7. Willing to adhere to the prohibitions and restrictions specified in this protocol

8. Patient must sign an informed consent form (ICF)

Exclusion Criteria:

1. Prior treatment with decitabine

2. Prior treatment with cytarabine

3. Prior treatment with pacritinib

4. Presence of serious illness, medical condition, or other medical history, involving the heart, kidney, liver, or other organ system, including abnormal laboratory parameters, which, in the opinion of the Investigator, would be likely to interfere with a subject's participation in the study or with the interpretation of the results.

5. Active, uncontrolled, clinically significant infection(s)

6. Have other active malignancies (excluding other myeloid hematologic malignancies) or other malignancies within 12 months before enrollment, except curatively treated non-melanoma skin cancer, cervical intraepithelial neoplasia, organ-confined or treated non-metastatic prostate cancer with negative prostate-specific antigen, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma

7. Are receiving any other investigational therapy or protocol-prohibited therapy

8. Any prior or co-existing medical condition that in the Investigator's judgment will substantially increase the risk associated with the subject's participation in the study

9. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures

10. Any gastrointestinal (GI) or metabolic condition that could interfere with absorption of oral medication

11. Inflammatory or chronic functional bowel disorder, such as Crohn's disease, inflammatory bowel disease, chronic diarrhea

12. Clinically symptomatic and uncontrolled cardiovascular disease

13. History of any of the following within 6 months: myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure

14. New York Heart Association Class III or IV congestive heart failure

15. Patients with National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) grade 2 cardiac arrhythmias may be considered for inclusion with the approval of the investigator if the arrhythmias are stable, asymptomatic and unlikely to affect patient safety. Patients will be excluded if they have ongoing cardiac dysrhythmias of CTCAE grade 3, corrected QT interval (QTc) prolongation >450 ms by Fridericia method, or other factors that increase the risk for QT prolongation (eg, heart failure, hypokalemia [defined as serum potassium < 3.0 milliequivalent (mEq/L) that is persistent and refractory to correction], or family history of long QT interval syndrome).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Weill Cornell Medical College	New York	New York	United States	10021

Sponsors and Collaborators

• Weill Medical College of Cornell University

Investigators

• Principal Investigator: SangMin Lee, MD, Weill Medical College of Cornell University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT02532010
• Other Study ID Numbers: 1403014921
• First Posted: Aug 25, 2015
• Last Update Posted: Jun 15, 2018
• Last Verified: Jun 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Cytarabine; Decitabine

Study Results

Participant Flow

Arm/Group Title	Arm A: Pacritinib and Decitiabine	Arm B: Pacritinib and Cytarabine
Arm/Group Description	Arm A: Each cycle: Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily. Pacritinib: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nM and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit JAK1. Decitabine: Commercial drug: For each cycle Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily.	Arm B: Each cycle: Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily. Pacritinib: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nM and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit JAK1. Cytarabine: Commercial drug: For each cycle Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily.
Period Title: Overall Study
STARTED	9	4
COMPLETED	0	0
NOT COMPLETED	9	4

Baseline Characteristics

Arm/Group Title	Arm A: Pacritinib and Decitiabine	Arm B: Pacritinib and Cytarabine	Total
Arm/Group Description	Arm A: Each cycle: Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily. Pacritinib: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nM and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit JAK1. Decitabine: Commercial drug: For each cycle Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily.	Arm B: Each cycle: Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily. Pacritinib: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nM and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit JAK1. Cytarabine: Commercial drug: For each cycle Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily.	Total of all reporting groups
Overall Participants	9	4	13
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	9 100%	4 100%	13 100%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	76	73	75
Sex: Female, Male (Count of Participants)
Female	5 55.6%	2 50%	7 53.8%
Male	4 44.4%	2 50%	6 46.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 11.1%	0 0%	1 7.7%
White	8 88.9%	2 50%	10 76.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	2 50%	2 15.4%
Region of Enrollment (Count of Participants)
United States	9 100%	4 100%	13 100%

Outcome Measures

1. Primary Outcome

Title	Complete Remission Rate
Description	Complete remission rate is defined as number of subjects with complete remission according to the IWG criteria, which is defined by presence of <5 percent of blasts in the bone marrow, absence of blasts with Auer rods, absence of extramedullary disease, absolute neutrophil count >1.0 x 109/L (1000/µL); platelet count >100 x 109/L (100,000/µL); independence of red cell transfusions.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A: Pacritinib and Decitiabine	Arm B: Pacritinib and Cytarabine
Arm/Group Description	Arm A: Each cycle: Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily. Pacritinib: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nM and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit JAK1. Decitabine: Commercial drug: For each cycle Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily.	Arm B: Each cycle: Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily. Pacritinib: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nM and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit JAK1. Cytarabine: Commercial drug: For each cycle Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily.
Measure Participants	9	4
Count of Participants [Participants]	0 0%	0 0%

2. Secondary Outcome

Title	Overall Survival
Description	Survival following treatment to the date of death
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A: Pacritinib and Decitiabine	Arm B: Pacritinib and Cytarabine
Arm/Group Description	Arm A: Each cycle: Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily. Pacritinib: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nM and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit JAK1. Decitabine: Commercial drug: For each cycle Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily.	Arm B: Each cycle: Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily. Pacritinib: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nM and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit JAK1. Cytarabine: Commercial drug: For each cycle Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily.
Measure Participants	9	4
Count of Participants [Participants]	3 33.3%	3 75%

3. Secondary Outcome

Title	Overall Remission Rate
Description	Overall remission rate is defined as number of subjects with complete remission (CR), Complete Remission with incomplete platelet recovery (CRp), Complete Remission with Incomplete Blood Count Recovery (CRi), Partial Remission (PR) according to the IWG criteria. CRi is defined as All CR criteria except for residual neutropenia (<1.0 x 109/L (1000/µL)) or thrombocytopenia (<100 x 109/L (100,000/µL)), PR is defined as relevant in the setting of phase I and II clinical trials only; all hematologic criteria of CR; decrease of bone marrow blast percentage to 5 to 25 percent; and decrease of pretreatment bone marrow blast percentage by at least 50 percent.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A: Pacritinib and Decitiabine	Arm B: Pacritinib and Cytarabine
Arm/Group Description	Arm A: Each cycle: Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily. Pacritinib: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nM and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit JAK1. Decitabine: Commercial drug: For each cycle Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily.	Arm B: Each cycle: Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily. Pacritinib: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nM and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit JAK1. Cytarabine: Commercial drug: For each cycle Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily.
Measure Participants	9	4
Count of Participants [Participants]	0 0%	0 0%

4. Secondary Outcome

Title	Relapse-free Survival
Description	Time from complete remission documentation to either AML relapse or death from any cause.
Time Frame	From date of complete remission until either AML relapse or death from any cause, whichever came first, assessed throughout the study period up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A: Pacritinib and Decitiabine	Arm B: Pacritinib and Cytarabine
Arm/Group Description	Arm A: Each cycle: Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily. Pacritinib: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nM and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit JAK1. Decitabine: Commercial drug: For each cycle Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily.	Arm B: Each cycle: Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily. Pacritinib: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nM and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit JAK1. Cytarabine: Commercial drug: For each cycle Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily.
Measure Participants	9	4
Median (Full Range) [months]	NA	NA

5. Secondary Outcome

Title	Event-free Survival
Description	Time from entry on study until time at which there is treatment failure, AML relapse, or death from any cause
Time Frame	Time from entry on study until time at which there is treatment failure, AML relapse, or death from any cause, assessed throughout the study period up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A: Pacritinib and Decitiabine	Arm B: Pacritinib and Cytarabine
Arm/Group Description	Arm A: Each cycle: Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily. Pacritinib: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nM and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit JAK1. Decitabine: Commercial drug: For each cycle Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily.	Arm B: Each cycle: Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily. Pacritinib: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nM and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit JAK1. Cytarabine: Commercial drug: For each cycle Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily.
Measure Participants	9	4
Median (Full Range) [months]	2.5	3

6. Secondary Outcome

Title	Time to Complete Response
Description	Time from entry on study until documentation of complete remission (CR)
Time Frame	From entry on study until complete remission, assessed throughout the study period up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A: Pacritinib and Decitiabine	Arm B: Pacritinib and Cytarabine
Arm/Group Description	Arm A: Each cycle: Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily. Pacritinib: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nM and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit JAK1. Decitabine: Commercial drug: For each cycle Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily.	Arm B: Each cycle: Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily. Pacritinib: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nM and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit JAK1. Cytarabine: Commercial drug: For each cycle Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily.
Measure Participants	9	4
Median (Full Range) [months]	NA	NA

7. Secondary Outcome

Title	Remission Duration
Description	Time from CR documentation to AML relapse
Time Frame	time from complete remission to AML relapse, assessed throughout the study period up to 2 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A: Pacritinib and Decitiabine	Arm B: Pacritinib and Cytarabine
Arm/Group Description	Arm A: Each cycle: Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily. Pacritinib: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nM and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit JAK1. Decitabine: Commercial drug: For each cycle Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily.	Arm B: Each cycle: Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily. Pacritinib: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nM and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit JAK1. Cytarabine: Commercial drug: For each cycle Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily.
Measure Participants	9	4
Median (Full Range) [months]	NA	NA

Adverse Events

Time Frame	2 years, 4 months
Arm/Group Title	Arm A: Pacritinib and Decitiabine		Arm B: Pacritinib and Cytarabine
Arm/Group Description	Arm A: Each cycle: Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily. Pacritinib: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nM and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit JAK1. Decitabine: Commercial drug: For each cycle Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily.		Arm B: Each cycle: Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily. Pacritinib: Pacritinib is a novel Janus kinase 2-fms-like receptor tyrosine kinase 3 (JAK2-FLT3) inhibitor that has shown promising antitumor activity. Pacritinib is a potent inhibitor of JAK2 and FLT3 kinase activities (50% inhibitory concentration (IC50) = 23 nM and 22 nM, respectively). The drug also inhibits cellular proliferation in human leukemia and lymphoma cell lines selected for their dependence on either of the target kinases. Consistent with these activities, exposure to pacritinib resulted in the reduction of phos-JAK2, phos-STAT3 or phos-STAT5 in the relevant cell lines. Unlike some JAK2 inhibitors, pacritinib does not inhibit JAK1. Cytarabine: Commercial drug: For each cycle Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily.
All Cause Mortality
	Arm A: Pacritinib and Decitiabine		Arm B: Pacritinib and Cytarabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/9 (100%)		4/4 (100%)
Serious Adverse Events
	Arm A: Pacritinib and Decitiabine		Arm B: Pacritinib and Cytarabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/9 (100%)		4/4 (100%)
Blood and lymphatic system disorders
neutropenic fever	2/9 (22.2%)	3	2/4 (50%)	4
Cardiac disorders
congestive heart failure	1/9 (11.1%)	1	0/4 (0%)	0
cardiopulmonary arrest	1/9 (11.1%)	1	0/4 (0%)	0
chest pain	1/9 (11.1%)	1	0/4 (0%)	0
Gastrointestinal disorders
dehydration/diarrhea	1/9 (11.1%)	1	0/4 (0%)	0
General disorders
fever	0/9 (0%)	0	1/4 (25%)	1
failure to thrive	1/9 (11.1%)	1	1/4 (25%)	1
fall	1/9 (11.1%)	1	1/4 (25%)	1
oral ulceration	1/9 (11.1%)	1	0/4 (0%)	0
Nervous system disorders
Dizziness and right shoulder pain	0/9 (0%)	0	1/4 (25%)	1
presyncope	0/9 (0%)	0	1/4 (25%)	1
dizziness	2/9 (22.2%)	2	0/4 (0%)	0
Psychiatric disorders
anxiety	1/9 (11.1%)	1	0/4 (0%)	0
Renal and urinary disorders
hematuria	1/9 (11.1%)	1	0/4 (0%)	0
Respiratory, thoracic and mediastinal disorders
acute respiratory failure	0/9 (0%)	0	1/4 (25%)	1
Other (Not Including Serious) Adverse Events
	Arm A: Pacritinib and Decitiabine		Arm B: Pacritinib and Cytarabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/9 (100%)		4/4 (100%)
Blood and lymphatic system disorders
Febrile Neutropenia	4/9 (44.4%)	8	3/4 (75%)	4
hypovolemia	1/9 (11.1%)	1	0/4 (0%)	0
coagulpathy	2/9 (22.2%)	2	0/4 (0%)	0
Cardiac disorders
chest pain	4/9 (44.4%)	4	2/4 (50%)	2
tachycardia	2/9 (22.2%)	2	0/4 (0%)	0
sinus tachycardia	2/9 (22.2%)	2	1/4 (25%)	1
congestive heart failure	1/9 (11.1%)	1	0/4 (0%)	0
NSVT	1/9 (11.1%)	1	0/4 (0%)	0
sinus bradycardia	1/9 (11.1%)	1	0/4 (0%)	0
cardiopulmonary arrest	1/9 (11.1%)	1	0/4 (0%)	0
bradycardia	2/9 (22.2%)	2	0/4 (0%)	0
prolonged QTc interval	1/9 (11.1%)	1	0/4 (0%)	0
intermittent chest palpitations	1/9 (11.1%)	1	0/4 (0%)	0
Eye disorders
right eye conjunctivitis	1/9 (11.1%)	1	0/4 (0%)	0
L eye ecchymoses	1/9 (11.1%)	1	0/4 (0%)	0
eye floaters	0/9 (0%)	0	1/4 (25%)	1
Gastrointestinal disorders
vomiting	4/9 (44.4%)	4	2/4 (50%)	5
constipation	7/9 (77.8%)	7	2/4 (50%)	2
mucositis	3/9 (33.3%)	3	3/4 (75%)	3
abdominal pain	1/9 (11.1%)	1	0/4 (0%)	0
Diarrhea	2/9 (22.2%)	2	0/4 (0%)	0
dysphagia	3/9 (33.3%)	3	1/4 (25%)	1
hemorrhoidal hemorrhage	1/9 (11.1%)	1	0/4 (0%)	0
internal hemorrhoids	1/9 (11.1%)	1	0/4 (0%)	0
loose stool	1/9 (11.1%)	1	2/4 (50%)	2
stomach burning	1/9 (11.1%)	1	0/4 (0%)	0
abdominal distension	2/9 (22.2%)	2	0/4 (0%)	0
decreased appetite	2/9 (22.2%)	2	0/4 (0%)	0
C. diff colitis	2/9 (22.2%)	2	0/4 (0%)	0
gas pain	1/9 (11.1%)	1	0/4 (0%)	0
stomach ache	1/9 (11.1%)	1	0/4 (0%)	0
rectal bleeding	1/9 (11.1%)	1	0/4 (0%)	0
R sided dental pain	1/9 (11.1%)	1	0/4 (0%)	0
General disorders
anorexia	3/9 (33.3%)	3	2/4 (50%)	4
fatigue	8/9 (88.9%)	8	2/4 (50%)	3
bleeding gums	1/9 (11.1%)	1	1/4 (25%)	1
dry mouth	4/9 (44.4%)	4	1/4 (25%)	1
fall	6/9 (66.7%)	6	4/4 (100%)	4
Chills	4/9 (44.4%)	4	3/4 (75%)	3
Fever	1/9 (11.1%)	1	1/4 (25%)	1
LE edema	5/9 (55.6%)	5	3/4 (75%)	3
loss of appetite	2/9 (22.2%)	2	2/4 (50%)	2
oral sore	1/9 (11.1%)	1	0/4 (0%)	0
rigors	2/9 (22.2%)	2	1/4 (25%)	1
non-specific body pain	1/9 (11.1%)	1	0/4 (0%)	0
great toe pain	1/9 (11.1%)	1	0/4 (0%)	0
right chest pain	1/9 (11.1%)	1	0/4 (0%)	0
left chest pain	1/9 (11.1%)	1	0/4 (0%)	0
pitting edema	1/9 (11.1%)	1	1/4 (25%)	1
intermittent swelling in feet	1/9 (11.1%)	1	0/4 (0%)	0
edema	0/9 (0%)	0	1/4 (25%)	1
fatigue upon exertion	0/9 (0%)	0	1/4 (25%)	1
sweats	0/9 (0%)	0	1/4 (25%)	1
hives following platelet transfusion	0/9 (0%)	0	1/4 (25%)	1
malaise	1/9 (11.1%)	1	0/4 (0%)	0
night sweats	2/9 (22.2%)	2	0/4 (0%)	0
Hepatobiliary disorders
gallstones	1/9 (11.1%)	1	0/4 (0%)	0
Infections and infestations
bacteremia	1/9 (11.1%)	1	2/4 (50%)	2
oral fungal infection	1/9 (11.1%)	1	0/4 (0%)	0
pruitic groin	1/9 (11.1%)	1	0/4 (0%)	0
pyuria	1/9 (11.1%)	1	0/4 (0%)	0
oral thrush	1/9 (11.1%)	1	0/4 (0%)	0
dysuria	1/9 (11.1%)	1	0/4 (0%)	0
mucocutaneous pain	1/9 (11.1%)	1	0/4 (0%)	0
genital herpes simplex	1/9 (11.1%)	1	0/4 (0%)	0
sepsis	1/9 (11.1%)	1	0/4 (0%)	0
VRE bacteremia	2/9 (22.2%)	2	0/4 (0%)	0
septic shock	0/9 (0%)	0	1/4 (25%)	1
polymicrobial sepsis	1/9 (11.1%)	1	0/4 (0%)	0
lung infection	0/9 (0%)	0	1/4 (25%)	1
Investigations
creatinine increased	2/9 (22.2%)	2	1/4 (25%)	1
Ejection fraction decreased	2/9 (22.2%)	2	1/4 (25%)	1
alkaline phosphatase increased	1/9 (11.1%)	1	0/4 (0%)	0
drug rash	2/9 (22.2%)	2	0/4 (0%)	0
hypernatremia	2/9 (22.2%)	2	0/4 (0%)	0
troponin I increased	1/9 (11.1%)	1	0/4 (0%)	0
hypophosphatemia	3/9 (33.3%)	3	1/4 (25%)	1
elevated lactate	0/9 (0%)	0	1/4 (25%)	1
Alanine aminotransferase increased	2/9 (22.2%)	2	0/4 (0%)	0
Aspartate aminotransferase increased	2/9 (22.2%)	2	0/4 (0%)	0
Blood bilirubin increased	1/9 (11.1%)	2	0/4 (0%)	0
hypoalbuminemia	2/9 (22.2%)	3	0/4 (0%)	0
hypocalcemia	1/9 (11.1%)	1	1/4 (25%)	1
hyperglycemia	1/9 (11.1%)	1	0/4 (0%)	0
increased LDH	1/9 (11.1%)	1	0/4 (0%)	0
Metabolism and nutrition disorders
hypomagnesemia	2/9 (22.2%)	2	1/4 (25%)	3
hypokalemia	2/9 (22.2%)	2	1/4 (25%)	2
Hyponatremia	2/9 (22.2%)	2	3/4 (75%)	4
hypomagnesemia	3/9 (33.3%)	3	2/4 (50%)	2
hyperphosphatemia	2/9 (22.2%)	2	0/4 (0%)	0
dehydration	2/9 (22.2%)	2	0/4 (0%)	0
Musculoskeletal and connective tissue disorders
bilateral leg cramps	1/9 (11.1%)	1	0/4 (0%)	0
back pain	1/9 (11.1%)	1	0/4 (0%)	0
trochanteric bursitis	1/9 (11.1%)	1	0/4 (0%)	0
generalized weakness	2/9 (22.2%)	3	1/4 (25%)	1
R shoulder pain	1/9 (11.1%)	1	0/4 (0%)	0
lower back pain	1/9 (11.1%)	1	1/4 (25%)	1
b/l LE weakness	0/9 (0%)	0	1/4 (25%)	1
R hip pain	1/9 (11.1%)	1	0/4 (0%)	0
body aches	2/9 (22.2%)	2	0/4 (0%)	0
Nervous system disorders
nausea	7/9 (77.8%)	7	4/4 (100%)	6
dizziness	4/9 (44.4%)	4	3/4 (75%)	4
presyncope	0/9 (0%)	0	1/4 (25%)	1
anxiety	3/9 (33.3%)	3	0/4 (0%)	0
hallucinations	2/9 (22.2%)	2	0/4 (0%)	0
tremors	1/9 (11.1%)	1	0/4 (0%)	0
numbness in feet	2/9 (22.2%)	2	0/4 (0%)	0
headache	0/9 (0%)	0	1/4 (25%)	1
lightheadedness	1/9 (11.1%)	3	1/4 (25%)	1
numbness in fingers	1/9 (11.1%)	1	0/4 (0%)	0
Psychiatric disorders
insomnia	6/9 (66.7%)	6	1/4 (25%)	1
confusion	1/9 (11.1%)	1	0/4 (0%)	0
depression	2/9 (22.2%)	2	0/4 (0%)	0
delirium	1/9 (11.1%)	1	0/4 (0%)	0
altered mental status	1/9 (11.1%)	1	0/4 (0%)	0
Renal and urinary disorders
non-obstructing renal calculi/hematuria	0/9 (0%)	0	1/4 (25%)	1
acute kidney injury	1/9 (11.1%)	1	2/4 (50%)	2
nocturia	1/9 (11.1%)	1	1/4 (25%)	1
hematuria	1/9 (11.1%)	1	1/4 (25%)	1
urinary retention	2/9 (22.2%)	2	0/4 (0%)	0
external hemorrhoids	2/9 (22.2%)	2	0/4 (0%)	0
increased urinary frequency	1/9 (11.1%)	1	0/4 (0%)	0
urinary distention	1/9 (11.1%)	1	0/4 (0%)	0
polyuria	1/9 (11.1%)	1	0/4 (0%)	0
oliguyric AKI	1/9 (11.1%)	1	0/4 (0%)	0
forceful urination	1/9 (11.1%)	1	0/4 (0%)	0
Respiratory, thoracic and mediastinal disorders
pneumonia	3/9 (33.3%)	3	2/4 (50%)	2
cough	5/9 (55.6%)	5	2/4 (50%)	2
epistaxis	3/9 (33.3%)	3	3/4 (75%)	3
pleuritic pain	2/9 (22.2%)	2	0/4 (0%)	0
sore throat	3/9 (33.3%)	3	1/4 (25%)	1
postnasal drip	4/9 (44.4%)	5	0/4 (0%)	0
pulmonary nodule	1/9 (11.1%)	1	0/4 (0%)	0
dyspnea on exertion	2/9 (22.2%)	2	0/4 (0%)	0
tachypnea	2/9 (22.2%)	2	0/4 (0%)	0
nasal congestion	2/9 (22.2%)	2	0/4 (0%)	0
wheezing	1/9 (11.1%)	1	1/4 (25%)	1
hypoxia	4/9 (44.4%)	4	1/4 (25%)	1
respiratory failure	1/9 (11.1%)	1	0/4 (0%)	0
pulmonary edema	1/9 (11.1%)	1	0/4 (0%)	0
rhinorrhea	2/9 (22.2%)	2	0/4 (0%)	0
acute respiratory failure	1/9 (11.1%)	1	1/4 (25%)	1
productive cough	1/9 (11.1%)	1	0/4 (0%)	0
dry nasal passages	1/9 (11.1%)	1	0/4 (0%)	0
dyspnea	1/9 (11.1%)	1	1/4 (25%)	1
hemoptysis	0/9 (0%)	0	1/4 (25%)	1
pleural effusions	0/9 (0%)	0	1/4 (25%)	1
pulmonary hemorrhage	0/9 (0%)	0	1/4 (25%)	1
pulmonary hypertension	0/9 (0%)	0	1/4 (25%)	1
atypical pneumonia	0/9 (0%)	0	1/4 (25%)	1
Skin and subcutaneous tissue disorders
ecchymosis on buttocks	0/9 (0%)	0	1/4 (25%)	1
maculo-papular rash	3/9 (33.3%)	3	0/4 (0%)	0
pruitis	1/9 (11.1%)	1	0/4 (0%)	0
hemorraghic bullae	1/9 (11.1%)	1	1/4 (25%)	1
Asteatotic eczema and xerosis lower legs and elbows	1/9 (11.1%)	1	0/4 (0%)	0
rash on trunk/legs	1/9 (11.1%)	1	0/4 (0%)	0
sacral pressure ulcer	1/9 (11.1%)	1	0/4 (0%)	0
dry skin	2/9 (22.2%)	2	0/4 (0%)	0
temporal wasting	1/9 (11.1%)	1	0/4 (0%)	0
nare lesion	1/9 (11.1%)	1	0/4 (0%)	0
intertrigo	1/9 (11.1%)	1	0/4 (0%)	0
toenail discoloration	1/9 (11.1%)	1	0/4 (0%)	0
bruising	1/9 (11.1%)	1	1/4 (25%)	1
oral herpes sore	1/9 (11.1%)	1	0/4 (0%)	0
petechiae on extremities	1/9 (11.1%)	1	2/4 (50%)	2
b/l feet purpura	0/9 (0%)	0	0/4 (0%)	0
blanching erythmatous rash on arm and back	0/9 (0%)	0	1/4 (25%)	1
rash on arms/legs	1/9 (11.1%)	1	0/4 (0%)	0
oral ulceration	1/9 (11.1%)	2	0/4 (0%)	0
sore on tongue	1/9 (11.1%)	1	0/4 (0%)	0
avulsed toenail	1/9 (11.1%)	1	0/4 (0%)	0
dry right sole of foot	1/9 (11.1%)	1	0/4 (0%)	0
diffuse rash on trunk	0/9 (0%)	0	1/4 (25%)	1
erythematous lesion on L forearm	0/9 (0%)	0	1/4 (25%)	1
b/l rash on groin	1/9 (11.1%)	1	0/4 (0%)	0
RLQ papular rash	1/9 (11.1%)	1	0/4 (0%)	0
Vascular disorders
orthostatic hypotension	1/9 (11.1%)	1	1/4 (25%)	1
hypertension	0/9 (0%)	0	1/4 (25%)	1
Phlebitis	1/9 (11.1%)	1	0/4 (0%)	0
hypotension	5/9 (55.6%)	5	1/4 (25%)	1
R wrist hematoma	0/9 (0%)	0	1/4 (25%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.