Trial Outcomes & Findings for Ruxolitinib for Adult T-Cell Leukemia (NCT NCT01712659)

Last Updated: 2023-01-10

Results Overview

Best response is complete response (CR) plus partial response (PR). Response was measured by the Revised Response Criteria for Lymphoma by Cheson, et al, and the International Consensus Meeting Criteria for Adult T-Cell Lymphoma (ATL). Complete response is disappearance of all clinical, microscopic, and radiographic evidence of disease. Partial response is a ≥50% reduction in the sum of the products of the greatest diameters of measurable disease without the appearance of new lesion. Stable disease is failure to attain complete response, partial response, or progressive disease. Progressive disease in peripheral blood is defined by a 50% increase from nadir in the count of flower cells and an absolute lymphocyte count, including flower cells, of 4x10\^9/L; or the appearance of new lesions excluding skin.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

19 participants

Primary outcome timeframe

From the time of the start of treatment to approximately 3 years of 5

Results posted on

2023-01-10

Participant Flow

No participants were enrolled on dose level 3 or the expansion cohort for the phase I dose escalation version of the protocol because the adult T-cell leukemia (ATL) research program was terminated after the death of the T-cell malignancy group Lead investigator.

Participant milestones

Participant milestones
Measure	Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.
Dose Escalation STARTED	1	5	1
Dose Escalation COMPLETED	1	3	1
Dose Escalation NOT COMPLETED	0	2	0
Dose Expansion STARTED	12	0	0
Dose Expansion COMPLETED	10	0	0
Dose Expansion NOT COMPLETED	2	0	0
Participants Re-Enrolled and Treated STARTED	0	1	0
Participants Re-Enrolled and Treated COMPLETED	0	1	0
Participants Re-Enrolled and Treated NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.
Dose Escalation Physician Decision	0	1
Dose Escalation Unable to take study drug	0	1
Dose Expansion Early disease progression	1	0
Dose Expansion Physician Decision	1	0

Baseline Characteristics

Ruxolitinib for Adult T-Cell Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily n=12 Participants Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily n=6 Participants Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily n=1 Participants Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Total n=19 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants	6 Participants n=7 Participants	1 Participants n=5 Participants	17 Participants n=4 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Age, Continuous	44.5 years STANDARD_DEVIATION 14.5 • n=5 Participants	46.3 years STANDARD_DEVIATION 10.9 • n=7 Participants	65 years STANDARD_DEVIATION 0 • n=5 Participants	51.93 years STANDARD_DEVIATION 12.7 • n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	9 Participants n=4 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	10 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	6 Participants n=7 Participants	1 Participants n=5 Participants	19 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants	5 Participants n=7 Participants	1 Participants n=5 Participants	18 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	12 participants n=5 Participants	6 participants n=7 Participants	1 participants n=5 Participants	19 participants n=4 Participants
Adult T-Cell Leukemia Lymphoma Diagnosis	12 Participants n=5 Participants	6 Participants n=7 Participants	1 Participants n=5 Participants	19 Participants n=4 Participants
Performance Status 0	5 Participants n=5 Participants	4 Participants n=7 Participants	0 Participants n=5 Participants	9 Participants n=4 Participants
Performance Status 1	7 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	10 Participants n=4 Participants
Prior Therapy Surgery	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Prior Therapy Chemotherapy	5 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	9 Participants n=4 Participants
Prior Therapy Radiation Therapy	5 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	6 Participants n=4 Participants
Prior Therapy Molecular	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Prior Therapy Immunotherapy	5 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	6 Participants n=4 Participants
Prior Therapy Treatment Naive	4 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	7 Participants n=4 Participants

PRIMARY outcome

Timeframe: From the time of the start of treatment to approximately 3 years of 5

Outcome measures

Outcome measures
Measure	Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily n=12 Participants Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily n=6 Participants Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily n=1 Participants Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.	Grade 1 - 2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 2 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 3 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 1 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 2 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 3 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.
Phase II: Best Response Complete Response	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—
Phase II: Best Response Partial Response	1 Participants	1 Participants	0 Participants	—	—	—	—	—	—	—	—	—
Phase II: Best Response Stable Disease	6 Participants	3 Participants	0 Participants	—	—	—	—	—	—	—	—	—
Phase II: Best Response Progressive Disease	5 Participants	0 Participants	1 Participants	—	—	—	—	—	—	—	—	—
Phase II: Best Response Not Assessable	0 Participants	2 Participants	0 Participants	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: From the time of the start of treatment to approximately 1 year

Population: No participants were treated in an expansion cohort (50mg) before the protocol was closed.

MTD is defined as the dose level at which no more than 1 of up to 6 participants experience dose-limiting toxicity (DLT) during the first cycle (28 days) treatment, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of the drug. A DLT is any grade 3 or 4 toxicity, if deemed possibly, probably, or definitely related to the study drug by the principal investigator during the first cycle of treatment with some exceptions such as Grade 3 anemia without hemolysis. Grade 3 or 4 granulocytopenia or leukopenia without infection, Grade 3 thrombocytopenia without bleeding, and Grade 3 or 4 lymphopenia. Grade 3 is severe or medically significant. Grade 4 is life-threatening, urgent intervention indicated.

Outcome measures

Outcome measures
Measure	Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily n=6 Participants Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily n=1 Participants Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.	Grade 1 - 2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 2 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 3 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 1 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 2 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 3 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.
Phase I: Maximum Tolerated Dose (MTD)	NA mg MTD was not defined because the Adult T-Cell Leukemia (ATL) project was terminated.	NA mg MTD was not defined because the Adult T-Cell Leukemia (ATL) project was terminated.	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From the time of the start of treatment to approximately 3 years

TTP is defined as the date of protocol consent until date of progressive disease is documented. Progressive disease was assessed by the Revised Response Criteria for Lymphoma by Cheson, et al, and the International Consensus Meeting Criteria for Adult T-Cell Lymphoma (guideline (version 1.1). Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, and the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily n=12 Participants Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily n=5 Participants Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily n=1 Participants Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.	Grade 1 - 2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 2 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 3 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 1 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 2 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 3 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.
Phase II: Time to Progression (TTP)	5.25 Months Standard Deviation 7.62	3.36 Months Standard Deviation 3.34	1 Months Standard Deviation NA Standard deviation is NA because it is only one participant.	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From the time of the start of treatment to approximately 3 years

Survival time is defined as the date of protocol consent until the date of the subject's death for any cause.

Outcome measures

Outcome measures
Measure	Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily n=12 Participants Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily n=6 Participants Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily n=1 Participants Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.	Grade 1 - 2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 2 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 3 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 1 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 2 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 3 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.
Phase II: Survival Time	29.3 Months Interval 15.7 to 42.9	20.1 Months Interval 3.9 to 36.3	14.1 Months 95% confidence interval cannot be calculated for one participant.	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From the time of the start of treatment to approximately 1 year

Grade of serious adverse events (SAEs) related to the experimental treatment. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, and Grade 4 is life-threatening.

Outcome measures

Outcome measures
Measure	Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily n=12 Participants Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily n=12 Participants Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily n=12 Participants Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily n=12 Participants Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.	Grade 1 - 2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily n=6 Participants Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 2 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily n=6 Participants Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 3 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily n=6 Participants Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily n=6 Participants Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 1 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily n=1 Participants Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 2 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily n=1 Participants Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 3 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily n=1 Participants Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily n=1 Participants Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.
Phase I: Grade of Serious and/or Non-serious Adverse Events (SAEs) Related to the Experimental Treatment by Grade Bilirubin increased	1 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events
Phase I: Grade of Serious and/or Non-serious Adverse Events (SAEs) Related to the Experimental Treatment by Grade White blood cells decreased	1 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	1 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	1 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events
Phase I: Grade of Serious and/or Non-serious Adverse Events (SAEs) Related to the Experimental Treatment by Grade Fatigue	1 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	1 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events
Phase I: Grade of Serious and/or Non-serious Adverse Events (SAEs) Related to the Experimental Treatment by Grade Nausea	1 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events
Phase I: Grade of Serious and/or Non-serious Adverse Events (SAEs) Related to the Experimental Treatment by Grade Anemia	2 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	1 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events
Phase I: Grade of Serious and/or Non-serious Adverse Events (SAEs) Related to the Experimental Treatment by Grade Alanine aminotransferase increased	3 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	1 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events
Phase I: Grade of Serious and/or Non-serious Adverse Events (SAEs) Related to the Experimental Treatment by Grade Aspartate aminotransferase increased	2 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	1 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events
Phase I: Grade of Serious and/or Non-serious Adverse Events (SAEs) Related to the Experimental Treatment by Grade Lymphocyte count decreased	3 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	1 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events
Phase I: Grade of Serious and/or Non-serious Adverse Events (SAEs) Related to the Experimental Treatment by Grade Platelet count decreased	1 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	1 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events
Phase I: Grade of Serious and/or Non-serious Adverse Events (SAEs) Related to the Experimental Treatment by Grade Creatinine increased	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	2 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events
Phase I: Grade of Serious and/or Non-serious Adverse Events (SAEs) Related to the Experimental Treatment by Grade Hypernatremia	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	1 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events
Phase I: Grade of Serious and/or Non-serious Adverse Events (SAEs) Related to the Experimental Treatment by Grade Alkaline phosphatase increased	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	1 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events
Phase I: Grade of Serious and/or Non-serious Adverse Events (SAEs) Related to the Experimental Treatment by Grade Neutrophil count decreased	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	1 Adverse Events	0 Adverse Events	0 Adverse Events	1 Adverse Events	0 Adverse Events	0 Adverse Events

SECONDARY outcome

Timeframe: From the time of the start of treatment to approximately 1 year

Population: No participants were enrolled on the expansion cohort for the phase I dose escalation (50mg) version of the protocol.

TTP is defined as the date of protocol consent until date of progressive disease is documented. Progressive disease was assessed by the Revised Response Criteria for Lymphoma by Cheson, et al, and the International Consensus Meeting Criteria for Adult T-Cell Lymphoma guidelines (version 1.1). Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, and the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily n=12 Participants Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily n=6 Participants Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily n=1 Participants Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.	Grade 1 - 2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 2 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 3 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 1 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 2 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 3 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.
Phase I: Time to Progression When Ruxolitinib is Administered at Doses of 30, 40 or 50 mg Orally Twice Daily	5.2 Months Interval 0.89 to 9.51	4.1 Months Interval 0.77 to 7.43	1 Months 95% confidence interval cannot be calculated for one participant.	—	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: During the first cycle of treatment (28 days)

A DLT is any grade 3 or 4 toxicity, if deemed possibly, probably or definitely related to the study drug by the principal investigator during the first cycle of treatment with some exceptions such as Grade 3 anemia without hemolysis. Grade 3 or 4 granulocytopenia or leukopenia without infection, Grade 3 thrombocytopenia without bleeding, and Grade 3 or 4 lymphopenia. Grade 3 is severe or medically significant. Grade 4 is life-threatening, urgent intervention indicated.

Outcome measures

Outcome measures
Measure	Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily n=12 Participants Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily n=6 Participants Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily n=1 Participants Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.	Grade 1 - 2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 2 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 3 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 1 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 2 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 3 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.
Number of Participants With a Dose Limiting Toxicity (DLT)	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Date treatment consent signed to date off study, approximately 110 months and 27 days.

Here is the number of participants with non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence.

Outcome measures

Outcome measures
Measure	Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily n=12 Participants Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily n=6 Participants Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily n=1 Participants Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.	Grade 1 - 2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 2 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 3 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 1 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 2 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 3 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	Grade 4 - 2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.
Number of Participants With Non-Serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0).	12 Participants	6 Participants	1 Participants	—	—	—	—	—	—	—	—	—

Adverse Events

Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily

Serious events: 0 serious events

Other events: 12 other events

Deaths: 11 deaths

2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily

Serious events: 0 serious events

Other events: 6 other events

Deaths: 3 deaths

2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Kevin C. Conlon

National Cancer Institute

Phone: 240-858-3570

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Original Phase II Standard Ruxolitinib Dose Cohort - 20 mg Twice Daily n=12 participants at risk Ruxolitinib 20 mg orally twice daily for 28 days. Subject may continue to receive treatment until progressive disease (PD) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 1 - 30 mg Twice Daily n=6 participants at risk Dose level 1: Ruxolitinib 30 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.	2- Phase 1 Dose Escalation Cohorts Dose Level 2 - 40 mg Twice Daily n=1 participants at risk Dose level 2: Ruxolitinib: Ruxolitinib 40 mg orally twice daily for 28 days to determine the maximum tolerated dose (MTD). Subjects may continue to receive treatment until progressive disease (PD) or dose limiting toxicity (DLT) or unacceptable toxicity.
Gastrointestinal disorders Abdominal pain	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Investigations Activated partial thromboplastin time prolonged	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Investigations Alanine aminotransferase increased	25.0% 3/12 • Number of events 5 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	33.3% 2/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Investigations Alkaline phosphatase increased	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Blood and lymphatic system disorders Anemia	25.0% 3/12 • Number of events 7 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Investigations Aspartate aminotransferase increased	25.0% 3/12 • Number of events 5 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Investigations Blood bilirubin increased	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Investigations Creatinine increased	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Nervous system disorders Dizziness	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
General disorders Edema limbs	16.7% 2/12 • Number of events 2 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Eye disorders Eye pain	0.00% 0/12 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
General disorders Fatigue	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
General disorders Fever	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Nervous system disorders Headache	0.00% 0/12 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Respiratory, thoracic and mediastinal disorders Hoarseness	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Metabolism and nutrition disorders Hyperglycemia	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Metabolism and nutrition disorders Hyperkalemia	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Metabolism and nutrition disorders Hypernatremia	0.00% 0/12 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Metabolism and nutrition disorders Hypoalbuminemia	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Metabolism and nutrition disorders Hypokalemia	16.7% 2/12 • Number of events 2 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Metabolism and nutrition disorders Hyponatremia	8.3% 1/12 • Number of events 2 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Metabolism and nutrition disorders Hypophosphatemia	16.7% 2/12 • Number of events 4 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Infections and infestations Infections and infestations - Other, Chikungunya virus	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Infections and infestations Infections and infestations - Other, Haemophilus influenzae bacteremia	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Infections and infestations Infections and infestations - Other, Shingles	0.00% 0/12 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
General disorders Infusion site extravasation	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Investigations Investigations - Other, Blood lactate dehydrogenase increased	0.00% 0/12 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Investigations Lymphocyte count decreased	58.3% 7/12 • Number of events 10 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	33.3% 2/6 • Number of events 3 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Investigations Lymphocyte count increased	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	16.7% 1/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Musculoskeletal and connective tissue disorders Myalgia	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Gastrointestinal disorders Nausea	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Investigations Neutrophil count decreased	50.0% 6/12 • Number of events 9 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	50.0% 3/6 • Number of events 3 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	100.0% 1/1 • Number of events 6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
General disorders Pain	33.3% 4/12 • Number of events 4 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/12 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Nervous system disorders Paresthesia	0.00% 0/12 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Investigations Platelet count decreased	16.7% 2/12 • Number of events 2 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Skin and subcutaneous tissue disorders Rash maculo-papular	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Investigations Serum amylase increased	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, callous buildup on toes (unsure if related to ATL)	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	8.3% 1/12 • Number of events 1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 110 months and 27 days.
Investigations White blood cell decreased	58.3% 7/12 • Number of events 7 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 110 months and 27 days.	100.0% 1/1 • Number of events 3 • Date treatment consent signed to date off study, approximately 110 months and 27 days.