Ruxolitinib Prior to Transplant in Patients With Myelofibrosis

• Sponsor: John Mascarenhas (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01790295
• Collaborator: Myeloproliferative Disorders-Research Consortium (Other), National Cancer Institute (NCI) (NIH), Incyte Corporation (Industry), Novartis (Industry)
• Enrollment: 21
• Locations: 8
• Arm: 1
• Duration (Months): 47.8
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to find out if giving the study drug Ruxolitinib (INC424) prior to a combination of other chemotherapeutic drugs (Fludarabine and Busulfan) before infusing another person's hematopoietic stem cells (bone marrow transplantation) will be successful in people who have advanced primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET-MF), collectively known as myelofibrosis (MF). MF is a disorder in which bone marrow tissue develops in abnormal sites because the bone marrow itself undergoes fibrosis or scarring. This study plans to evaluate whether adding the drug Ruxolitinib will further aid in reducing pre-transplant spleen size, improve physical performance levels and reduce adverse events (side effects) related to the transplant. Ruxolitinib is a drug that is approved by the FDA for the treatment of patients with advanced forms of myelofibrosis. Using Ruxolitinib prior to stem cell transplantation is experimental.

Condition or Disease	Intervention/Treatment	Phase
Primary Myelofibrosis; Post Polycythemia Vera Myelofibrosis; Post Essential Thrombocythemia Myelofibrosis	Drug: Ruxolitinib Pre- Hematopoietic cell transplantation (HCT)	Phase 2

Detailed Description

A two- stage Simon Phase II study will be conducted in each of two groups of patients:

related and unrelated donor transplants. In each donor transplant group, the first stage of this design will include 11 patients evaluated for death or graft failure by 100 days post-transplant. In each stratum, we will enroll additional patients (up to 20%) of stratum total to take into account exclusions due to donor failure (such as donor deemed unsuitable for stem cell donation due to medical or other reasons) only. Those patients who have toxicities related to Ruxolitinib and not been able to reach HCT due to these toxicities will be included in the estimation of overall failure rates. Only those patients who are excluded based on donor related issues without any regimen related complications will be excluded from the estimation of failure rates. However, all data on these patients will be reported.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Exploring the Potential of Dual Kinase JAK 1/2 Inhibitor Ruxolitinib (INC424) With Reduced Intensity Allogeneic Hematopoietic Cell Transplantation in Patients With Myelofibrosis
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Oct 26, 2017
• Actual Study Completion Date: Oct 26, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) Ruxolitinib (INC424) tablets will be started 62 days (day -67) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib will be determined according to baseline platelet count and will be modified according to platelet count at follow-up. The drug will be given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and will be stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug will be supplied as 5 mg tablets.

Drug: Ruxolitinib Pre- Hematopoietic cell transplantation (HCT); Ruxolitinib (INC424) tablets will be started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib will be determined according to baseline platelet count and will be modified according to platelet count at follow-up. The drug will be given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and will be stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug will be supplied as 5 mg tablets.; Other Names: Ruxolitinib \Pre- Hematopoietic cell transplantation (HCT) INC424

Outcome Measures

Primary Outcome Measures

1. Percent of Participants With 100-day Survival Without Graft Failure [Day 100-post allogeneic stem cell transplantation]

   The feasibility of combining Ruxolitinib (INC424) with a Reduced intensity conditioning (RIC) regimen likely to produce success post transplantation, success being defined as patient being alive, and without graft failure at day 100-post allogeneic stem cell transplantation (in patients who receive (a) related donor transplant and in those who receive (b) an unrelated donor transplant.

Secondary Outcome Measures

1. Time to Neutrophil Recovery [up to 4 years]

   Neutrophil recovery will be defined as first of the three consecutive days with neutrophil count ≥0.5 x 109/l.

2. Platelet Recovery [up to 4 years]

   Platelet recovery will be defined as first of the 7 days with platelet count ≥20 x 109/l, without platelet transfusion support and both maintained for 30 days without transfusion support or myeloid cytokine support.

3. Percent of Participants With Non-relapse Mortality (NRM) [100 days]

   NRM will be defined as death in first 30 days due to any cause, and subsequently death due to any cause without the recurrence or progression of myelofibrosis. Cumulative incidence of NRM will be calculated taking relapse/progression as competing event.

4. Percent of Participants With Non-relapse Mortality (NRM) [1-year post transplant]

   NRM will be defined as death in first 30 days due to any cause, and subsequently death due to any cause without the recurrence or progression of myelofibrosis. Cumulative incidence of NRM will be calculated taking relapse/progression as competing event.

5. Percent of Participants With Graft Versus Host Disease (GvHD) [1-year post transplant]

   Acute and chronic GvHD. GvHD is a potentially serious complication of allogeneic stem cell transplantation. Stage Skin Liver (bilirubin) Gut (stool output/day) 0 No GVHD rash < 2 mg/dl < 500 ml/day or persistent nausea. Maculopapular rash< 25% body surface area (BSA) 2-3 mg/dl 500-999 ml/day Maculopapular rash 25 - 50% BSA 3.1-6 mg/dl 1000-1500 ml/day Maculopapular rash > 50% BSA 6.1-15 mg/dl Adult: >1500 ml/day Generalized erythroderma plus bullous formation >15 mg/dl Severe abdominal pain with or without ileus Grade I Stage 1-2 None None II Stage 3 or Stage 1 or Stage 1 III - Stage 2-3 or Stage 2-4 IV Stage 4 or Stage 4 -

6. Chimerism Studies [30 days post transplant]

   Will check percentage of donor versus recipient blood cells to determine efficacy of donor engraftment

7. Chimerism Studies [60 days post transplant]

   Will check percentage of donor versus recipient blood cells to determine efficacy of donor engraftment

8. Chimerism Studies [100 days post transplant]

   Will check percentage of donor versus recipient blood cells to determine efficacy of donor engraftment

9. Number of Participants With Remission Status According to IWG-MRT Criteria [Day 100 post transplant]

   Remission status according to International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria Remission defined as: Bone marrow:* Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF and Peripheral blood: Hemoglobin ≥100 g/L and <UNL; neutrophil count ≥ 1 × 109/L and <UNL; Platelet count ≥100 × 109/L and <UNL; <2% immature myeloid cells and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of extramedullary hematopoiesis (EMH)

10. Number of Participants With Remission Status at 6 Months Post Transplant [6 months post transplant]

    Remission defined as: Bone marrow:* Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF† and Peripheral blood: Hemoglobin ≥100 g/L and <UNL; neutrophil count ≥ 1 × 109/L and <UNL; Platelet count ≥100 × 109/L and <UNL; <2% immature myeloid cells‡ and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH

11. Number of Participants With Remission Status at 12 Months Post Transplant [12 months post transplant]

    Remission defined as: Bone marrow:* Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF† and Peripheral blood: Hemoglobin ≥100 g/L and <UNL; neutrophil count ≥ 1 × 109/L and <UNL; Platelet count ≥100 × 109/L and <UNL; <2% immature myeloid cells‡ and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH

12. Number of Participants With Relapse/Progression (Defined as Per IWG-MRT Criteria) [1-year post transplant]

    Relapse/progression defined as: Peripheral blood: Hemoglobin ≥100 g/L and <UNL; neutrophil count ≥1 × 109/L and <UNL; platelet count ≥100 × 109/L and <UNL; <2% immature myeloid cells‡ and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH or Bone marrow:* Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF†, and peripheral blood: Hemoglobin ≥85 but <100 g/L and <UNL; neutrophil count ≥1 × 109/L and <UNL; platelet count ≥50, but <100 × 109/L and <UNL; <2% immature myeloid cells‡ and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH

13. Number of Participants With Progression-free Survival [1-year post transplant]

    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

14. Number of Overall Survival [1-year post transplant]

15. Mean Change in the Brief Fatigue Inventory Score [baseline and 48 months]

    Mean change in the Brief Fatigue Inventory score (BFI) from baseline to 48 months to assess impact of allogeneic stem cell transplant on myelofibrosis associated symptoms and overall quality of life. The BFI is a 9 item scored from 0 (no fatigue) -10 (as bad as you can imagine), items are averaged with total score from 0-10, with higher score indicating more fatigue.

16. Expression Profiling and Measurements of Cytokines Prior to Start of Ruxolitinib, Prior to Start of Chemotherapy for Conditioning [30 days post transplant]

17. Expression Profiling and Measurements of Cytokines Prior to Start of Ruxolitinib, Prior to Start of Chemotherapy for Conditioning [100 days post transplant]

18. Association of Cytokines Levels With Acute and Chronic GvHD [30 days post transplant]

19. Association of Cytokines Levels With Acute and Chronic GvHD [100 days post transplant]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Documented diagnosis of primary myelofibrosis according to WHO criteria or post PV myelofibrosis or post ET myelofibrosis as per IWG-MRT criteria

• Age 18-70 years

• Intermediate-2/ high-risk disease as per Dynamic IPSS (DIPSS) criteria OR Intermediate-1 risk disease with one of the following additional unfavorable features known to impact the survival adversely

1. Red cell transfusion dependency

2. Unfavorable Karyotype

3. Platelet count <100 x 109/l

• Blasts in the PB and BM ≤10% prior to study enrollment

• Availability of a suitable matched related (6/6 or 5/6) or unrelated donor (10/10 or 9/10 antigen or allele matched).

• Able to give informed written consent

• ECOG Performance status of 0-2.

• Life expectancy >3 months

• Off all MF-directed therapy including investigational agents for at least 2 weeks prior to study enrollment and recovered from all toxicities*

• Adequate organ function

• Adequate renal function - creatinine <1.5 x IULN

• Adequate hepatic function - AST/ALT <2.5 x IULN, Total Bilirubin <1.5 x IULN

• Adequate hematopoietic function - Platelet ≥50 x 109/l and ANC ≥1.0 x 109/l

• LVEF >40% (MUGA or echocardiogram) Normal per Institutional standard

• Adequate pulmonary function with DLCO >50%

• A patient who has been on stable dose of Ruxolitinib and has received ruxolitinib ≤6 months prior to the study entry will be considered potentially eligible for the study with the caveat that there is no evidence of loss of response (>5cm increase in spleen size from the nadir).

Exclusion Criteria:

• Any previous JAK2 inhibitor treatment prior to study enrollment, with the exception of Ruxolitinib

• Hypersensitivity to JAK inhibitor

• Clinical or laboratory evidence of cirrhosis

• Prior allogeneic transplant for any hematopoietic disorder

• 20% blast in the PB or BM prior to HCT or had leukemic transformation (>20% blasts in PB or BM any time prior to HCT)

• Syngeneic donor

• Cord Blood transplant

• Active uncontrolled infection

• H/o another malignancy within 5-years of date of HCT except h/o basal cell or squamous cell carcinoma of skin or PV or ET

• Known HIV positive

• Pregnancy at the time of BMT

• Any other concurrent illness which in investigator's opinion puts the patient at excessive risk of treatment related toxicities

• Unable to give informed consent

• Active infection with hepatitis A,B or C virus

• Subjects who require therapy with a strong CYP3A4 inhibitor prior to enrollment to this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory Hospital	Atlanta	Georgia	United States	30322
2	Northwestern University, Robert h. Lurie Comprehensive Cancer Center	Chicago	Illinois	United States	60611
3	University of Kansas Cancer Center	Westwood	Kansas	United States	66205
4	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
5	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina	United States	27103
6	Ohio State University	Columbus	Ohio	United States	43210
7	Princess Margaret Cancer Centre, University of Toronto	Toronto		Canada	M5G 2M9
8	University of Oxford	Oxford		United Kingdom	OX3 9DS

Sponsors and Collaborators

• John Mascarenhas
• Myeloproliferative Disorders-Research Consortium
• National Cancer Institute (NCI)
• Incyte Corporation
• Novartis

Investigators

• Principal Investigator: John Mascarenhas, MD, Icahn School of Medicine at Mount Sinai
• Study Chair: Vikas Gupta, MD, FRCP, FRCPath, University of Toronto
• Study Chair: Adam Mead, MD, University of Oxford, John Radcliffe Hospital

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Aug 8, 2016

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: John Mascarenhas, Associate Professor, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT01790295
• Other Study ID Numbers: GCO 12-1809; MPD-RC 114
• First Posted: Feb 13, 2013
• Last Update Posted: Mar 20, 2019
• Last Verified: Feb 1, 2019

• Keywords provided by John Mascarenhas, Associate Professor, Icahn School of Medicine at Mount Sinai: Myelofibrosis; Stem cell transplant; Ruxolitinib
• Additional relevant MeSH terms: Polycythemia Vera; Primary Myelofibrosis; Polycythemia; Thrombocytosis; Thrombocythemia, Essential

Study Results

Participant Flow

Recruitment Details	Recruitment began in February 2013, with first enrollment in November 2013.

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis. Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Period Title: Overall Study
STARTED	21
COMPLETED	10
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Overall Participants	21
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59
Sex: Female, Male (Count of Participants)
Female	11 52.4%
Male	10 47.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 4.8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 4.8%
White	19 90.5%
More than one race	0 0%
Unknown or Not Reported	0 0%
Diagnosis (Count of Participants)
Primary myelofibrosis	10 47.6%
Post-PV myelofibrosis	3 14.3%
Post-ET myelofibrosis	8 38.1%
Donor type (Count of Participants)
Related donor	7 33.3%
Unrelated donor	14 66.7%
ECOG status (Count of Participants)
0	9 42.9%
1	12 57.1%

Outcome Measures

1. Primary Outcome

Title	Percent of Participants With 100-day Survival Without Graft Failure
Description	The feasibility of combining Ruxolitinib (INC424) with a Reduced intensity conditioning (RIC) regimen likely to produce success post transplantation, success being defined as patient being alive, and without graft failure at day 100-post allogeneic stem cell transplantation (in patients who receive (a) related donor transplant and in those who receive (b) an unrelated donor transplant.
Time Frame	Day 100-post allogeneic stem cell transplantation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Measure Participants	21
Number (95% Confidence Interval) [percentage of participants]	74 352.4%

2. Secondary Outcome

Title	Time to Neutrophil Recovery
Description	Neutrophil recovery will be defined as first of the three consecutive days with neutrophil count ≥0.5 x 109/l.
Time Frame	up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Measure Participants	21
Median (95% Confidence Interval) [days]	23

3. Secondary Outcome

Title	Platelet Recovery
Description	Platelet recovery will be defined as first of the 7 days with platelet count ≥20 x 109/l, without platelet transfusion support and both maintained for 30 days without transfusion support or myeloid cytokine support.
Time Frame	up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Measure Participants	21
Median (95% Confidence Interval) [days]	30

4. Secondary Outcome

Title	Percent of Participants With Non-relapse Mortality (NRM)
Description	NRM will be defined as death in first 30 days due to any cause, and subsequently death due to any cause without the recurrence or progression of myelofibrosis. Cumulative incidence of NRM will be calculated taking relapse/progression as competing event.
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Measure Participants	21
Number (95% Confidence Interval) [percentage of participants]	16 76.2%

5. Secondary Outcome

Title	Percent of Participants With Non-relapse Mortality (NRM)
Description	NRM will be defined as death in first 30 days due to any cause, and subsequently death due to any cause without the recurrence or progression of myelofibrosis. Cumulative incidence of NRM will be calculated taking relapse/progression as competing event.
Time Frame	1-year post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Measure Participants	21
Number (95% Confidence Interval) [percentage of participants]	28 133.3%

6. Secondary Outcome

Title	Percent of Participants With Graft Versus Host Disease (GvHD)
Description	Acute and chronic GvHD. GvHD is a potentially serious complication of allogeneic stem cell transplantation. Stage Skin Liver (bilirubin) Gut (stool output/day) 0 No GVHD rash < 2 mg/dl < 500 ml/day or persistent nausea. Maculopapular rash< 25% body surface area (BSA) 2-3 mg/dl 500-999 ml/day Maculopapular rash 25 - 50% BSA 3.1-6 mg/dl 1000-1500 ml/day Maculopapular rash > 50% BSA 6.1-15 mg/dl Adult: >1500 ml/day Generalized erythroderma plus bullous formation >15 mg/dl Severe abdominal pain with or without ileus Grade I Stage 1-2 None None II Stage 3 or Stage 1 or Stage 1 III - Stage 2-3 or Stage 2-4 IV Stage 4 or Stage 4 -
Time Frame	1-year post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Measure Participants	21
Acute GvHD (Grade 1/2)	48 228.6%
Acute GvHD (Grade 3)	16 76.2%
Chronic GvHD (Mild)	51 242.9%
Chronic (Moderate)	25 119%

7. Secondary Outcome

Title	Chimerism Studies
Description	Will check percentage of donor versus recipient blood cells to determine efficacy of donor engraftment
Time Frame	30 days post transplant

Outcome Measure Data

Analysis Population Description

This data was not collected because the study ended early.

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Measure Participants	0

8. Secondary Outcome

Title	Chimerism Studies
Description	Will check percentage of donor versus recipient blood cells to determine efficacy of donor engraftment
Time Frame	60 days post transplant

Outcome Measure Data

Analysis Population Description

This data was not collected because the study ended early.

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis
Measure Participants	0

9. Secondary Outcome

Title	Chimerism Studies
Description	Will check percentage of donor versus recipient blood cells to determine efficacy of donor engraftment
Time Frame	100 days post transplant

Outcome Measure Data

Analysis Population Description

This data was not collected because the study ended early.

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Measure Participants	0

10. Secondary Outcome

Title	Number of Participants With Remission Status According to IWG-MRT Criteria
Description	Remission status according to International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria Remission defined as: Bone marrow:* Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF and Peripheral blood: Hemoglobin ≥100 g/L and <UNL; neutrophil count ≥ 1 × 109/L and <UNL; Platelet count ≥100 × 109/L and <UNL; <2% immature myeloid cells and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of extramedullary hematopoiesis (EMH)
Time Frame	Day 100 post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Measure Participants	21
Count of Participants [Participants]	20 95.2%

11. Secondary Outcome

Title	Number of Participants With Remission Status at 6 Months Post Transplant
Description	Remission defined as: Bone marrow:* Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF† and Peripheral blood: Hemoglobin ≥100 g/L and <UNL; neutrophil count ≥ 1 × 109/L and <UNL; Platelet count ≥100 × 109/L and <UNL; <2% immature myeloid cells‡ and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH
Time Frame	6 months post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Measure Participants	21
Count of Participants [Participants]	17 81%

12. Secondary Outcome

Title	Number of Participants With Remission Status at 12 Months Post Transplant
Description	Remission defined as: Bone marrow:* Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF† and Peripheral blood: Hemoglobin ≥100 g/L and <UNL; neutrophil count ≥ 1 × 109/L and <UNL; Platelet count ≥100 × 109/L and <UNL; <2% immature myeloid cells‡ and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH
Time Frame	12 months post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Measure Participants	21
Count of Participants [Participants]	14 66.7%

13. Secondary Outcome

Title	Number of Participants With Relapse/Progression (Defined as Per IWG-MRT Criteria)
Description	Relapse/progression defined as: Peripheral blood: Hemoglobin ≥100 g/L and <UNL; neutrophil count ≥1 × 109/L and <UNL; platelet count ≥100 × 109/L and <UNL; <2% immature myeloid cells‡ and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH or Bone marrow:* Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF†, and peripheral blood: Hemoglobin ≥85 but <100 g/L and <UNL; neutrophil count ≥1 × 109/L and <UNL; platelet count ≥50, but <100 × 109/L and <UNL; <2% immature myeloid cells‡ and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH
Time Frame	1-year post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Measure Participants	21
Count of Participants [Participants]	7 33.3%

14. Secondary Outcome

Title	Number of Participants With Progression-free Survival
Description	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	1-year post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Measure Participants	21
Count of Participants [Participants]	11 52.4%

15. Secondary Outcome

Title	Number of Overall Survival
Time Frame	1-year post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Measure Participants	21
Count of Participants [Participants]	15 71.4%

16. Secondary Outcome

Title	Mean Change in the Brief Fatigue Inventory Score
Description	Mean change in the Brief Fatigue Inventory score (BFI) from baseline to 48 months to assess impact of allogeneic stem cell transplant on myelofibrosis associated symptoms and overall quality of life. The BFI is a 9 item scored from 0 (no fatigue) -10 (as bad as you can imagine), items are averaged with total score from 0-10, with higher score indicating more fatigue.
Time Frame	baseline and 48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Measure Participants	21
Mean (95% Confidence Interval) [score on a scale]	1.7

17. Secondary Outcome

Title	Expression Profiling and Measurements of Cytokines Prior to Start of Ruxolitinib, Prior to Start of Chemotherapy for Conditioning
Time Frame	30 days post transplant

Outcome Measure Data

Analysis Population Description

This data was not collected because the study ended early.

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Measure Participants	0

18. Secondary Outcome

Title	Expression Profiling and Measurements of Cytokines Prior to Start of Ruxolitinib, Prior to Start of Chemotherapy for Conditioning
Time Frame	100 days post transplant

Outcome Measure Data

Analysis Population Description

This data was not collected because the study ended early.

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Measure Participants	0

19. Secondary Outcome

Title	Association of Cytokines Levels With Acute and Chronic GvHD
Time Frame	30 days post transplant

Outcome Measure Data

Analysis Population Description

This data was not collected because the study ended early.

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Measure Participants	0

20. Secondary Outcome

Title	Association of Cytokines Levels With Acute and Chronic GvHD
Time Frame	100 days post transplant

Outcome Measure Data

Analysis Population Description

This data was not collected because the study ended early.

Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
Measure Participants	0

Adverse Events

Time Frame	up to 4 years
Arm/Group Title	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
Arm/Group Description	Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) in Patients With Myelofibrosis Ruxolitinib (INC424) tablets started 60 days (day -65) prior to start of conditioning chemotherapy. The starting dose of Ruxolitinib was determined according to baseline platelet count and modified according to platelet count at follow-up. The drug was given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion. The drug was supplied as 5 mg tablets.
All Cause Mortality
	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
	Affected / at Risk (%)	# Events
Total	4/21 (19%)
Serious Adverse Events
	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
	Affected / at Risk (%)	# Events
Total	13/21 (61.9%)
Endocrine disorders
Drug-induced hyperglycemia	1/21 (4.8%)
Gastrointestinal disorders
Diverticulitis NOS	1/21 (4.8%)
Nausea post chemotherapy	1/21 (4.8%)
General disorders
Death sudden	1/21 (4.8%)
Neutropenic fever	1/21 (4.8%)
Disease Progression	1/21 (4.8%)
Infections and infestations
Pneumonia	4/21 (19%)
Sepsis	3/21 (14.3%)
Injury, poisoning and procedural complications
Graft failure	4/21 (19%)
Investigations
Elevated liver enzyme levels	1/21 (4.8%)
Lymphocyte count decreased	1/21 (4.8%)
Metabolism and nutrition disorders
Hyponatremia	1/21 (4.8%)
Nervous system disorders
Intracranial hemorrhage	1/21 (4.8%)
Spinal epidural hematoma	1/21 (4.8%)
Renal and urinary disorders
Acute renal failure	1/21 (4.8%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/21 (4.8%)
Pneumonia	1/21 (4.8%)
Other (Not Including Serious) Adverse Events
	Ruxolitinib Pre- Hematopoietic Cell Transplantation (HCT)
	Affected / at Risk (%)	# Events
Total	20/21 (95.2%)
Blood and lymphatic system disorders
Acute myeloid leukemia	1/21 (4.8%)
Anemia	13/21 (61.9%)
Febrile neutropenia	6/21 (28.6%)
Hemolysis	1/21 (4.8%)
Iron deficiency anemia	1/21 (4.8%)
Leukopenia	1/21 (4.8%)
Petechiae	4/21 (19%)
Thrombocytopenia	4/21 (19%)
Autoimmune hemolytic anemia	1/21 (4.8%)
Cardiac disorders
Cardiomyopathy	1/21 (4.8%)
Chest pain - cardiac	1/21 (4.8%)
Palpitations	1/21 (4.8%)
Presyncope	1/21 (4.8%)
Sinus tachycardia	4/21 (19%)
Syncope	2/21 (9.5%)
Tachycardia	1/21 (4.8%)
Ear and labyrinth disorders
Ear pain	2/21 (9.5%)
Hearing impaired	1/21 (4.8%)
Middle ear inflammation	1/21 (4.8%)
Endocrine disorders
Insufficiency adrenal	1/21 (4.8%)
Eye disorders
Blurred vision	2/21 (9.5%)
Cataract	1/21 (4.8%)
Conjunctivitis	1/21 (4.8%)
Double vision	1/21 (4.8%)
Drug-induced liver disease	1/21 (4.8%)
Dry eye	1/21 (4.8%)
Night blindness	11/21 (52.4%)
Scleral hemorrhage	2/21 (9.5%)
Gastrointestinal disorders
Abdominal pain	9/21 (42.9%)
Anal hemorrhage	3/21 (14.3%)
Bloating	5/21 (23.8%)
C.difficile diarrhea	1/21 (4.8%)
Constipation	4/21 (19%)
Diarrhea	11/21 (52.4%)
Dry mouth	6/21 (28.6%)
Dysgeusia	1/21 (4.8%)
Dyspepsia	5/21 (23.8%)
Dysphagia	2/21 (9.5%)
Fecal incontinence	2/21 (9.5%)
Flatulence	2/21 (9.5%)
Hemorrhoidal hemorrhage	2/21 (9.5%)
Irritation lips	1/21 (4.8%)
Left lower quadrant pain	1/21 (4.8%)
Mucositis oral	8/21 (38.1%)
Nausea	14/21 (66.7%)
Nausea and vomiting	1/21 (4.8%)
Oral hemorrhage	1/21 (4.8%)
Perianal pain	1/21 (4.8%)
Sore throat	4/21 (19%)
Tooth pain	1/21 (4.8%)
Vomiting	7/21 (33.3%)
General disorders
Catheter site erythema	1/21 (4.8%)
Chills	6/21 (28.6%)
Diaphoresis	1/21 (4.8%)
Edema extremities	8/21 (38.1%)
Fatigue	8/21 (38.1%)
Fever	8/21 (38.1%)
Lethargy	1/21 (4.8%)
Malaise	2/21 (9.5%)
Night sweats	2/21 (9.5%)
Non-cardiac chest pain	1/21 (4.8%)
Pain	4/21 (19%)
Post procedural discomfort	1/21 (4.8%)
Rigors	1/21 (4.8%)
Weakness	1/21 (4.8%)
Edematous weight gain	1/21 (4.8%)
Hepatobiliary disorders
Hypoalbuminemia	8/21 (38.1%)
Immune system disorders
Alloimmunization	1/21 (4.8%)
Bronchospasm	1/21 (4.8%)
Cytokine release syndrome	2/21 (9.5%)
Polymyalgia rheumatica	1/21 (4.8%)
Urticaria	1/21 (4.8%)
Infections and infestations
CMV infection	1/21 (4.8%)
Clostridium difficile test positive	1/21 (4.8%)
HSV infection	1/21 (4.8%)
Infusion site cellulitis	1/21 (4.8%)
Respiratory syncytial virus infection	12/21 (57.1%)
Sepsis	1/21 (4.8%)
Skin infection	1/21 (4.8%)
Upper respiratory tract infection bacterial	3/21 (14.3%)
Urinary tract infection	2/21 (9.5%)
Injury, poisoning and procedural complications
Fall	2/21 (9.5%)
Foot injury	1/21 (4.8%)
Open wound of foot except toe(s) alone	1/21 (4.8%)
Investigations
Activated partial thromboplastin time	5/21 (23.8%)
Alanine aminotransferase increased	7/21 (33.3%)
Alkaline phosphatase increased	7/21 (33.3%)
Blood bilirubin increased	5/21 (23.8%)
Creatinine increased	4/21 (19%)
Fibrinogen decreased	1/21 (4.8%)
Hemoglobin decreased	1/21 (4.8%)
INR increased	5/21 (23.8%)
Increased TSH	1/21 (4.8%)
Laboratory test abnormal	1/21 (4.8%)
Lymphocyte count decreased	5/21 (23.8%)
Lymphocyte count increased	1/21 (4.8%)
Neutrophil count decreased	9/21 (42.9%)
Plasma creatinine increased	1/21 (4.8%)
Platelet count decreased	10/21 (47.6%)
Weight gain	1/21 (4.8%)
Weight loss	5/21 (23.8%)
White blood cell decreased	9/21 (42.9%)
Aspartate aminotransferase increased	8/21 (38.1%)
White blood cell count increased	1/21 (4.8%)
Metabolism and nutrition disorders
Anorexia	7/21 (33.3%)
Dehydration	1/21 (4.8%)
GGT Increased	1/21 (4.8%)
Gout	1/21 (4.8%)
Hyperglycemia	9/21 (42.9%)
Hyperkalemia	8/21 (38.1%)
Hypermagnesemia	1/21 (4.8%)
Hypertension	6/21 (28.6%)
Hypertriglyceridemia	1/21 (4.8%)
Hyperuricemia	4/21 (19%)
Hypoalbuminemia	8/21 (38.1%)
Hypocalcemia	3/21 (14.3%)
Hypokalemia	5/21 (23.8%)
Hypomagnesaemia	10/21 (47.6%)
Hyponatremia	6/21 (28.6%)
Hypophosphatemia	5/21 (23.8%)
Musculoskeletal and connective tissue disorders
Ankle edema	2/21 (9.5%)
Arthralgia	3/21 (14.3%)
Back pain (without radiation)	6/21 (28.6%)
Bone pain	2/21 (9.5%)
Generalized muscle weakness	5/21 (23.8%)
Muscle weakness lower limb	3/21 (14.3%)
Neck pain	1/21 (4.8%)
Pseudogout	1/21 (4.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cardiac neoplasm unspecified	1/21 (4.8%)
Nervous system disorders
Agitation	1/21 (4.8%)
Burning sensation	1/21 (4.8%)
Confusion	2/21 (9.5%)
Dizziness	8/21 (38.1%)
Headache	8/21 (38.1%)
Insomnia	2/21 (9.5%)
Paraplegia	1/21 (4.8%)
Peripheral motor neuropathy	1/21 (4.8%)
Peripheral sensory neuropathy	1/21 (4.8%)
Sleep apnea	1/21 (4.8%)
Somnolence	2/21 (9.5%)
Tremor	2/21 (9.5%)
Urinary incontinence	2/21 (9.5%)
Syncope	2/21 (9.5%)
Psychiatric disorders
Anxiety	2/21 (9.5%)
Confusion	2/21 (9.5%)
Delirium	1/21 (4.8%)
Depression	4/21 (19%)
Renal and urinary disorders
Acute kidney injury	4/21 (19%)
Acute renal failure	1/21 (4.8%)
Burning from urination	1/21 (4.8%)
Chronic kidney disease	1/21 (4.8%)
Hematuria	2/21 (9.5%)
Painful urination	1/21 (4.8%)
Renal calculi	1/21 (4.8%)
Urinary hesitancy	1/21 (4.8%)
Urinary incontinence	2/21 (9.5%)
Reproductive system and breast disorders
Gynecomastia	1/21 (4.8%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	3/21 (14.3%)
Chest congestion	1/21 (4.8%)
Cough	6/21 (28.6%)
Dyspnea	10/21 (47.6%)
Epistaxis	5/21 (23.8%)
Hiccups	2/21 (9.5%)
Hoarseness	1/21 (4.8%)
Hypoxia	1/21 (4.8%)
Lung infection	1/21 (4.8%)
Nasal congestion	3/21 (14.3%)
Pharyngitis	1/21 (4.8%)
Pleural effusion	1/21 (4.8%)
Pleuritic pain	1/21 (4.8%)
Postnasal drip	1/21 (4.8%)
Respiratory failure	1/21 (4.8%)
Sinusitis	1/21 (4.8%)
Sneezing	1/21 (4.8%)
Sore throat	4/21 (19%)
Wheezing	4/21 (19%)
Skin and subcutaneous tissue disorders
Allergic rash	1/21 (4.8%)
Bruising	5/21 (23.8%)
Dry skin	6/21 (28.6%)
Erythema	3/21 (14.3%)
Facial swelling	1/21 (4.8%)
Folliculitis	2/21 (9.5%)
Itching	1/21 (4.8%)
Maculopapular rash	3/21 (14.3%)
Periocular rash	1/21 (4.8%)
Pressure sore	1/21 (4.8%)
Pruritus	5/21 (23.8%)
Rash acneiform	1/21 (4.8%)
Skin desquamation	1/21 (4.8%)
Skin hyperpigmentation	1/21 (4.8%)
Skin lesion	1/21 (4.8%)
Skin ulcer	1/21 (4.8%)
Edema periorbital	1/21 (4.8%)
Macular Rash	1/21 (4.8%)
Petechiae	4/21 (19%)
Vascular disorders
Contusion	1/21 (4.8%)
Hematoma	1/21 (4.8%)
Hypotension	2/21 (9.5%)
Lightheadedness	1/21 (4.8%)
Orthostatic hypotension	1/21 (4.8%)

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.