Ruxolitinib Phosphate and Decitabine in Treating Patients With Relapsed or Refractory or Post Myeloproliferative Acute Myeloid Leukemia

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02257138
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 30
• Location: 1
• Arms: 2
• Actual Duration (Months): 73.2
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This phase I/II trial studies the side effects and best dose of ruxolitinib phosphate when given together with decitabine and to see how well they work in treating patients with acute myeloid leukemia that has come back or is not responding to treatment, or has developed from a type of bone marrow diseases called myeloproliferative neoplasms. Ruxolitinib phosphate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ruxolitinib phosphate together with decitabine may be an effective treatment for acute myeloid leukemia.

Condition or Disease	Intervention/Treatment	Phase
Blasts More Than 20 Percent of Bone Marrow Nucleated Cells; Blasts More Than 20 Percent of Peripheral Blood White Cells; Myelodysplastic/Myeloproliferative Neoplasm; Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia	Drug: Decitabine; Other: Laboratory Biomarker Analysis; Drug: Ruxolitinib Phosphate	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the tolerability of the combination of decitabine and ruxolitinib phosphate (ruxolitinib [DI]) in patients with leukemia. (Phase I) II. To determine the efficacy of ruxolitinib in increasing and prolonging response induced by decitabine alone in patients with post myeloproliferative neoplasm acute myeloid leukemia (AML) (post MPN-AML) alternatively referred to as (myeloproliferative neoplasm - blast phase; MPN-BP). (Compared to historical response rate with decitabine alone) (Phase II)

SECONDARY OBJECTIVES:

1. To compare whether there is a difference in response rate patients with post-MPN AML with janus kinase 2 (JAK2) mutations and patients without JAK2 mutations.

OUTLINE: This is a phase I, dose-escalation study of ruxolitinib phosphate followed by a phase II study.

Patients receive ruxolitinib phosphate orally (PO) twice daily (BID) on days 1-28 and decitabine intravenously (IV) over 1-2 hours on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Study of Ruxolitinib Plus Decitabine in Patients With Post Myeloproliferative Neoplasm - Acute Myeloid Leukemia (AML)
• Actual Study Start Date: Feb 12, 2015
• Actual Primary Completion Date: Mar 19, 2021
• Actual Study Completion Date: Mar 19, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (ruxolitinib phosphate, decitabine) Ph1 Patients receive ruxolitinib phosphate PO BID on days 1-28 and decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity.	Drug: Decitabine; Given IV; Other Names: 5-Aza-2'-deoxycytidine Aza-TdC Dacogen Decitabine for Injection Deoxyazacytidine Dezocitidine ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Ruxolitinib Phosphate; Given PO; Other Names: INCB-18424 Phosphate Jakafi
Experimental: Treatment (ruxolitinib phosphate, decitabine) Ph2 Patients receive 50mg ruxolitinib phosphate PO BID on days 1-28 and decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity.	Drug: Decitabine; Given IV; Other Names: 5-Aza-2'-deoxycytidine Aza-TdC Dacogen Decitabine for Injection Deoxyazacytidine Dezocitidine ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Ruxolitinib Phosphate; Given PO; Other Names: INCB-18424 Phosphate Jakafi

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose of Ruxolitinib Phosphate (Phase I) [Up to 6 weeks]

   Maximum tolerated dose (MTD) is defined as the highest dose studied for which the incidence of dose-limiting toxicity (DLT) is less than or equal to 17% (1 out of 6).

2. Number of Participants With a Response (Complete Response [CR] + CR With Incomplete Blood Count Recovery) (Phase 2) [Up to 6 years]

   Complete Response (CR) is defined as - The participant must be free of all symptoms related to leukemia and have an absolute neutrophil count >/= 1 z 10^9/L, no need for red blood cell transfusion, platelet count>/+ 100 x 10^9/L, and normal marrow differential (</= 5 % blasts) in a normo- or hypercellular marrow. Complete Response with incomplete blood count recovery (CRi) is defined as - Same as CR but incomplete count recovery.

3. Number of Participants With Post-MPN Acute Myeloid Leukemia (AML) With JAK2 Mutations (Phase 2) [Baseline]

   JAK2 mutations were assessed with the baseline Bone Marrow or Peripheral Blood.

Secondary Outcome Measures

1. Number of JAK2 Positive+ and JAK2 Negative- Participants With a Response (Phase 2) [up to 6 years]

   JAK2 mutations were assessed with the baseline Bone Marrow or Peripheral Blood. Complete Response (CR) is defined as - The participant must be free of all symptoms related to leukemia and have an absolute neutrophil count >/= 1 z 10^9/L, no need for red blood cell transfusion, platelet count>/+ 100 x 10^9/L, and normal marrow differential (</= 5 % blasts) in a normo- or hypercellular marrow. Complete Response with incomplete blood count recovery (CRi) is defined as - Same as CR but incomplete count recovery.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of AML (World Health Organization [WHO] classification definition of >= to 20% blasts)

• In the phase I portion of the study all patients with relapsed or refractory AML are eligible; for the Phase II portion of the study, patients must have AML progressing from prior MPN (MPN-BP) or have myelodysplastic syndrome (MDS)/MPN with more than 20% blasts; temporary prior measures to control blood counts, such as apheresis or Hydrea are allowed; patients with newly diagnosed or previously treated disease are eligible as long as prior therapy does not include hypomethylating agents; prior therapy for ruxolitinib for MPN is allowed

• Serum biochemical values with the following limits unless considered due to leukemia:

• Creatinine =< 1.5 mg/dl

• Total bilirubin =< 1.5 mg/dL, unless increase is due to hemolysis or congenital disorder

• Transaminases (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x upper limit of normal (ULN)

• Ability to take oral medication

• Ability to understand and provide signed informed consent

• Performance status =< 3, unless directly related to disease process as determined by the principal investigator

Exclusion Criteria:

• Any coexisting medical condition that in the judgment of the treating physician is likely to interfere with study procedures or results including uncontrolled severe infections, as well as uncontrolled cardiac disease, or other organ dysfunction; patients with history of tuberculosis, human immunodeficiency virus (HIV) or hepatitis B and C are excluded

• Nursing women, women of childbearing potential with positive blood pregnancy test within 30 days of study start, or women of childbearing potential who are not willing to maintain adequate contraception (such as birth control pills, intrauterine device [IUD], diaphragm, abstinence, or condoms by their partner) over the entire course of the study

• Incomplete recovery from any prior surgical procedures or had surgery within 4 weeks prior to study entry, excluding the placement of vascular access

• Active clinically serious and uncontrolled infection

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Farhad Ravandi-Kashani, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 16, 2015

More Information

Additional Information:

• MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT02257138
• Other Study ID Numbers: 2014-0344; NCI-2014-02299; 2014-0344
• First Posted: Oct 6, 2014
• Last Update Posted: Aug 15, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Leukemia; Neoplasms; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Decitabine

Study Results

Participant Flow

Recruitment Details	Treatment Period: February 2015 to March 2021

Arm/Group Title	Ph1 (MTD) 10mg	Ph1 (MTD) 15mg	Ph1 (MTD) 25mg	Ph1 (MTD) 50mg	Ph2 Treatment (Ruxolitinib Phosphate, Decitabine)
Arm/Group Description	Patients receive ruxolitinib phosphate PO BID on days 1-28 and decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Decitabine: Given IV Laboratory Biomarker Analysis: Correlative studies Ruxolitinib Phosphate: Given PO	Patients receive ruxolitinib phosphate PO BID on days 1-28 and decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Decitabine: Given IV Laboratory Biomarker Analysis: Correlative studies Ruxolitinib Phosphate: Given PO	Patients receive ruxolitinib phosphate PO BID on days 1-28 and decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Decitabine: Given IV Laboratory Biomarker Analysis: Correlative studies Ruxolitinib Phosphate: Given PO	Patients receive ruxolitinib phosphate PO BID on days 1-28 and decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Decitabine: Given IV Laboratory Biomarker Analysis: Correlative studies Ruxolitinib Phosphate: Given PO	Patients receive ruxolitinib phosphate PO BID on days 1-28 and decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Decitabine: Given IV Laboratory Biomarker Analysis: Correlative studies Ruxolitinib Phosphate: Given PO
Period Title: Overall Study
STARTED	5	3	3	3	16
COMPLETED	5	3	3	3	16
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Ph1 (MTD) 10mg	Ph1 (MTD) 15mg	Ph1 (MTD) 25mg	Ph1 (MTD) 50mg	Ph2 Treatment (Ruxolitinib Phosphate, Decitabine)	Total
Arm/Group Description	Patients receive ruxolitinib phosphate PO BID on days 1-28 and decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Decitabine: Given IV Laboratory Biomarker Analysis: Correlative studies Ruxolitinib Phosphate: Given PO	Patients receive ruxolitinib phosphate PO BID on days 1-28 and decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Decitabine: Given IV Laboratory Biomarker Analysis: Correlative studies Ruxolitinib Phosphate: Given PO	Patients receive ruxolitinib phosphate PO BID on days 1-28 and decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Decitabine: Given IV Laboratory Biomarker Analysis: Correlative studies Ruxolitinib Phosphate: Given PO	Patients receive ruxolitinib phosphate PO BID on days 1-28 and decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Decitabine: Given IV Laboratory Biomarker Analysis: Correlative studies Ruxolitinib Phosphate: Given PO	Patients receive 50mg ruxolitinib phosphate PO BID on days 1-28 and 20mg/m^2 decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Decitabine: Given IV Laboratory Biomarker Analysis: Correlative studies Ruxolitinib Phosphate: Given PO	Total of all reporting groups
Overall Participants	5	3	3	3	16	30
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	1 20%	0 0%	1 33.3%	2 66.7%	7 43.8%	11 36.7%
>=65 years	4 80%	3 100%	2 66.7%	1 33.3%	9 56.3%	19 63.3%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	84	69	77	61	69	69
Sex: Female, Male (Count of Participants)
Female	3 60%	1 33.3%	1 33.3%	0 0%	6 37.5%	11 36.7%
Male	2 40%	2 66.7%	2 66.7%	3 100%	10 62.5%	19 63.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	1 33.3%	0 0%	3 18.8%	4 13.3%
White	5 100%	3 100%	2 66.7%	3 100%	10 62.5%	23 76.7%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	3 18.8%	3 10%
Region of Enrollment (participants) [Number]
United States	5 100%	3 100%	3 100%	3 100%	16 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose of Ruxolitinib Phosphate (Phase I)
Description	Maximum tolerated dose (MTD) is defined as the highest dose studied for which the incidence of dose-limiting toxicity (DLT) is less than or equal to 17% (1 out of 6).
Time Frame	Up to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ph1 (MTD) Treatment (Ruxolitinib Phosphate, Decitabine)
Arm/Group Description	Patients receive ruxolitinib phosphate PO BID on days 1-28 and decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Decitabine: Given IV Laboratory Biomarker Analysis: Correlative studies Ruxolitinib Phosphate: Given PO
Measure Participants	14
Number [Dose in Milligrams]	NA

2. Primary Outcome

Title	Number of Participants With a Response (Complete Response [CR] + CR With Incomplete Blood Count Recovery) (Phase 2)
Description	Complete Response (CR) is defined as - The participant must be free of all symptoms related to leukemia and have an absolute neutrophil count >/= 1 z 10^9/L, no need for red blood cell transfusion, platelet count>/+ 100 x 10^9/L, and normal marrow differential (</= 5 % blasts) in a normo- or hypercellular marrow. Complete Response with incomplete blood count recovery (CRi) is defined as - Same as CR but incomplete count recovery.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ph2 Treatment (Ruxolitinib Phosphate, Decitabine)
Arm/Group Description	Patients receive 50mg ruxolitinib phosphate PO BID on days 1-28 and 20mg/m^2 decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Decitabine: Given IV Laboratory Biomarker Analysis: Correlative studies Ruxolitinib Phosphate: Given PO
Measure Participants	16
Count of Participants [Participants]	8 160%

3. Primary Outcome

Title	Number of Participants With Post-MPN Acute Myeloid Leukemia (AML) With JAK2 Mutations (Phase 2)
Description	JAK2 mutations were assessed with the baseline Bone Marrow or Peripheral Blood.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ph2 Treatment (Ruxolitinib Phosphate, Decitabine)
Arm/Group Description	Patients receive 50mg ruxolitinib phosphate PO BID on days 1-28 and 20mg/m^2 decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Decitabine: Given IV Laboratory Biomarker Analysis: Correlative studies Ruxolitinib Phosphate: Given PO
Measure Participants	16
Count of Participants [Participants]	11 220%

4. Secondary Outcome

Title	Number of JAK2 Positive+ and JAK2 Negative- Participants With a Response (Phase 2)
Description	JAK2 mutations were assessed with the baseline Bone Marrow or Peripheral Blood. Complete Response (CR) is defined as - The participant must be free of all symptoms related to leukemia and have an absolute neutrophil count >/= 1 z 10^9/L, no need for red blood cell transfusion, platelet count>/+ 100 x 10^9/L, and normal marrow differential (</= 5 % blasts) in a normo- or hypercellular marrow. Complete Response with incomplete blood count recovery (CRi) is defined as - Same as CR but incomplete count recovery.
Time Frame	up to 6 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ph2 Treatment (Ruxolitinib Phosphate, Decitabine)
Arm/Group Description	Patients receive 50mg ruxolitinib phosphate PO BID on days 1-28 and 20mg/m^2 decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Decitabine: Given IV Laboratory Biomarker Analysis: Correlative studies Ruxolitinib Phosphate: Given PO
Measure Participants	8
JAK 2+ Positive	5 100%
JAK 2- negative	3 60%

Adverse Events

Time Frame	Up to 6 years
Arm/Group Title	Ph1 (MTD) 10mg		Ph1 (MTD) 15mg		Ph1 (MTD) 25mg		Ph1 (MTD) 50mg		Ph2 Treatment (Ruxolitinib Phosphate, Decitabine)
Arm/Group Description	Patients receive ruxolitinib phosphate PO BID on days 1-28 and decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Decitabine: Given IV Laboratory Biomarker Analysis: Correlative studies Ruxolitinib Phosphate: Given PO		Patients receive ruxolitinib phosphate PO BID on days 1-28 and decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Decitabine: Given IV Laboratory Biomarker Analysis: Correlative studies Ruxolitinib Phosphate: Given PO		Patients receive ruxolitinib phosphate PO BID on days 1-28 and decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Decitabine: Given IV Laboratory Biomarker Analysis: Correlative studies Ruxolitinib Phosphate: Given PO		Patients receive ruxolitinib phosphate PO BID on days 1-28 and decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Decitabine: Given IV Laboratory Biomarker Analysis: Correlative studies Ruxolitinib Phosphate: Given PO		Patients receive 50mg ruxolitinib phosphate PO BID on days 1-28 and 20mg/m^2 decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Decitabine: Given IV Laboratory Biomarker Analysis: Correlative studies Ruxolitinib Phosphate: Given PO
All Cause Mortality
	Ph1 (MTD) 10mg		Ph1 (MTD) 15mg		Ph1 (MTD) 25mg		Ph1 (MTD) 50mg		Ph2 Treatment (Ruxolitinib Phosphate, Decitabine)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40%)		3/3 (100%)		1/3 (33.3%)		2/3 (66.7%)		2/16 (12.5%)
Serious Adverse Events
	Ph1 (MTD) 10mg		Ph1 (MTD) 15mg		Ph1 (MTD) 25mg		Ph1 (MTD) 50mg		Ph2 Treatment (Ruxolitinib Phosphate, Decitabine)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/5 (60%)		3/3 (100%)		3/3 (100%)		3/3 (100%)		11/16 (68.8%)
Blood and lymphatic system disorders
Blood and Lymphatic System Disorders	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/16 (6.3%)	1
Febrile Neutropenia	1/5 (20%)	1	1/3 (33.3%)	1	0/3 (0%)	0	1/3 (33.3%)	1	3/16 (18.8%)	5
Cardiac disorders
Atrial fibrillation	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/16 (6.3%)	1
Supraventricular and nodal arrhythmia	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/16 (6.3%)	1
Gastrointestinal disorders
Colitis	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	2/16 (12.5%)	2
Upper Gastrointestinal Hemorrhage	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/16 (6.3%)	2
General disorders
Fatigue	0/5 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/16 (0%)	0
Fever	0/5 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	1	1/3 (33.3%)	2	0/16 (0%)	0
Infections and infestations
Infection	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	2/16 (12.5%)	2
Lung Infection	2/5 (40%)	3	2/3 (66.7%)	4	3/3 (100%)	3	0/3 (0%)	0	5/16 (31.3%)	9
Sepsis	0/5 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	1/3 (33.3%)	1	1/16 (6.3%)	1
Soft Tissue Infection	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	2/16 (12.5%)	2
Injury, poisoning and procedural complications
Fracture	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/16 (0%)	0
Spinal Fracture	0/5 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/16 (0%)	0
Metabolism and nutrition disorders
Hypercalcemia	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/16 (6.3%)	1
Musculoskeletal and connective tissue disorders
Muscle Weakness	0/5 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/16 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung Adenocarcinoma	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/16 (6.3%)	1
Nervous system disorders
Intracranial Hemorrhage	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/16 (6.3%)	1
Renal and urinary disorders
Acute Kidney Injury	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/16 (0%)	0
Skin and subcutaneous tissue disorders
Lower Extremity Rash	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/16 (6.3%)	1
Vascular disorders
Hypotension	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/16 (0%)	0
Other (Not Including Serious) Adverse Events
	Ph1 (MTD) 10mg		Ph1 (MTD) 15mg		Ph1 (MTD) 25mg		Ph1 (MTD) 50mg		Ph2 Treatment (Ruxolitinib Phosphate, Decitabine)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		3/3 (100%)		3/3 (100%)		3/3 (100%)		11/16 (68.8%)
Blood and lymphatic system disorders
Febrile Neutropenia	0/5 (0%)	0	2/3 (66.7%)	2	0/3 (0%)	0	0/3 (0%)	0	1/16 (6.3%)	2
Cardiac disorders
Cardiac Arrythmia	0/5 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/16 (0%)	0
Gastrointestinal disorders
Anorexia	0/5 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	1	1/3 (33.3%)	1	0/16 (0%)	0
Constipation	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	4/16 (25%)	4
Diarrhea	2/5 (40%)	2	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/16 (6.3%)	1
Dry Mouth	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/16 (0%)	0
Hemorrhage Gastrointestial	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/16 (6.3%)	1
Mucositis	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/16 (6.3%)	1
Nausea	2/5 (40%)	2	1/3 (33.3%)	1	1/3 (33.3%)	1	0/3 (0%)	0	2/16 (12.5%)	2
General disorders
Bruising	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/16 (0%)	0
Edema Limbs	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	1	1/16 (6.3%)	1
Fatigue	2/5 (40%)	2	2/3 (66.7%)	2	0/3 (0%)	0	0/3 (0%)	0	0/16 (0%)	0
Hemorrhage Other	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/16 (0%)	0
Pain	1/5 (20%)	1	2/3 (66.7%)	2	0/3 (0%)	0	1/3 (33.3%)	3	2/16 (12.5%)	2
Petechiae	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/16 (0%)	0
Weight loss	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/16 (0%)	0
Infections and infestations
Infection	3/5 (60%)	3	2/3 (66.7%)	4	0/3 (0%)	0	0/3 (0%)	0	1/16 (6.3%)	1
Investigations
Alkaline Phosphatase	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/16 (0%)	0
Elevated Bilirubin	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	2/16 (12.5%)	2
Elevated Creatinine	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/16 (0%)	0
Metabolism and nutrition disorders
Hypercalcemia	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/16 (6.3%)	1
Hyperglycemia	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/16 (0%)	0
Hyperkalemia	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/16 (0%)	0
Hyponatremia	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/16 (0%)	0
Nervous system disorders
Dizziness	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/16 (0%)	0
Renal and urinary disorders
Renal Failure	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/16 (6.3%)	1
Renal/Genitourinary Other	0/5 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/16 (0%)	0
Skin and subcutaneous tissue disorders
Pruritis/itching	1/5 (20%)	1	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/16 (0%)	0
Vascular disorders
Hypotension	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/16 (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.