Trial Outcomes & Findings for CC-4047 in Treating Patients With Myelofibrosis (NCT NCT00669578)

Last Updated: 2019-12-30

Results Overview

Starting at a dose level of 2.5 mg/d on days 1-21 in every 28 day cycle, participants were accrued in cohorts of three to assess dose limiting toxicities (DLT) and determine the maximum tolerated dose (MTD). Dose escalation at increments of 0.5 mg/d was done if no subject had a DLT (a grade 4 or higher hematologic toxicity or a grade 3 or higher febrile neutropenia or a grade 3 or higher non-hematologic toxicity) in cycle 1. Subsequent cohorts were treated until the maximum tolerated dose (MTD) was reached (dose level before that which results in a DLT in \>1 of 6 subjects). Subsequent participants were treated at the MTD, those without response at the MTD after 3 cycles were lowered to the minimal efficacious dose (MED) of 0.5 mg daily. Here, we are reporting the percentage of participants in Phase I with a DLT at each dose level.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

77 participants

Primary outcome timeframe

The first 28-day cycle of treatment.

Results posted on

2019-12-30

Participant Flow

This study opened June 2008 and accrued 12 Phase I participants and 65 Phase II participants before being closed in January 2010.

Participants were accrued to the Phase I portion of this study in each of the 2.5, 3.0, and 3.5 mg dose cohorts. Dose Limiting Toxicities (DLT) were observed at the 3.5 mg level, and the 3 mg level was confirmed as the maximum tolerated dose. However, efficacy was not improved at higher doses and the most effective dose level was deemed 0.5 mg/day.

Participant milestones

Participant milestones
Measure	Phase I Participants were accrued to the Phase I portion of this study in each of the 2.5, 3.0, and 3.5 mg dose cohorts to determine the Maximum Tolerated Dose (MTD). Dose limiting Toxicities (DLT) were observed at the 3.5 mg level, and the 3 mg level was confirmed as the maximum tolerated dose. For this study a DLT was defined as a grade 4 hematologic toxicity, a grade 3 or higher febrile neutropenia, or a grade 3 or higher non-hematologic toxicity.	Phase II All patients enrolled to this phase II arm started treatment at 0.5mg/day with CC-4047 every day of each 28 day cycle.
Overall Study STARTED	12	65
Overall Study COMPLETED	12	65
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

CC-4047 in Treating Patients With Myelofibrosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase II n=65 Participants All patients enrolled to this Phase II arm started treatment at 0.5mg/day with CC-4047 every day of each 28 day cycle.	Phase I n=12 Participants Participants were accrued to the Phase I portion of this study in each of the 2.5, 3.0, and 3.5 mg dose cohorts to determine the Maximum Tolerated Dose (MTD). Dose limiting Toxicities (DLT) were observed at the 3.5 mg level, and the 3 mg level was confirmed as the maximum tolerated dose. For this study a DLT was defined as a grade 4 hematologic toxicity, a grade 3 or higher febrile neutropenia, or a grade 3 or higher non-hematologic toxicity.	Total n=77 Participants Total of all reporting groups
Age, Continuous	68 years FULL_RANGE 9.7 • n=5 Participants	66 years n=7 Participants	67 years n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	7 Participants n=7 Participants	25 Participants n=5 Participants
Sex: Female, Male Male	47 Participants n=5 Participants	5 Participants n=7 Participants	52 Participants n=5 Participants
Region of Enrollment United States	65 participants n=5 Participants	12 participants n=7 Participants	77 participants n=5 Participants

PRIMARY outcome

Timeframe: The first 28-day cycle of treatment.

Population: None of the Phase II participants were evaluable for this endpoint. For the Phase I portion of this study, three participants were accrued at a 2.5 mg/day dose level, six at the 3.0 mg/day dose level, and three at the 3.5 mg/day dose level.

Outcome measures

Outcome measures
Measure	Phase I n=12 Participants Participants were accrued to the Phase I portion of this study in each of the 2.5, 3.0, and 3.5 mg dose cohorts to determine the Maximum Tolerated Dose (MTD). Dose limiting Toxicities (DLT) were observed at the 3.5 mg level, and the 3 mg level was confirmed as the maximum tolerated dose. For this study a DLT was defined as a grade 4 hematologic toxicity, a grade 3 or higher febrile neutropenia, or a grade 3 or higher non-hematologic toxicity.	Phase II All patients enrolled to this phase II arm started treatment at 0.5mg/day with CC-4047 every day of each 28 day cycle.
Determine the Maximum Tolerated Dose of CC-4047 2.5 mg/day	0 percentage of participants with DLT	—
Determine the Maximum Tolerated Dose of CC-4047 3.0 mg/day	0 percentage of participants with DLT	—
Determine the Maximum Tolerated Dose of CC-4047 3.5 mg/day	66 percentage of participants with DLT	—

PRIMARY outcome

Timeframe: Every cycle of treatment for 6 cycles. Each cycle is 28 days.

Population: None of the participants from the Phase I cohort were analyzed for this endpoint. All 65 Phase II participants were evaluable for this endpoint and included in the analysis.

Response evaluation: Complete Remission (CR): Neutrophil count between 1 to 10 x 10\^9/L without peripheral blasts in blood or bone marrow. Partial Hematologic Response/Partial Remission (PR): Increase in neutrophil by 50% + above 10\^9/L for neutropenia) Clinical Improvement (CI): Increase in Neutrophil count, hemoglobin, platelet count or reduction in blood/marrow blasts.

Outcome measures

Outcome measures
Measure	Phase I n=65 Participants Participants were accrued to the Phase I portion of this study in each of the 2.5, 3.0, and 3.5 mg dose cohorts to determine the Maximum Tolerated Dose (MTD). Dose limiting Toxicities (DLT) were observed at the 3.5 mg level, and the 3 mg level was confirmed as the maximum tolerated dose. For this study a DLT was defined as a grade 4 hematologic toxicity, a grade 3 or higher febrile neutropenia, or a grade 3 or higher non-hematologic toxicity.	Phase II All patients enrolled to this phase II arm started treatment at 0.5mg/day with CC-4047 every day of each 28 day cycle.
Best Overall Response Over the First 6 Cycles of Treatment Complete Remission	0 participants	—
Best Overall Response Over the First 6 Cycles of Treatment Partial Remission	0 participants	—
Best Overall Response Over the First 6 Cycles of Treatment Clinical Improvement	9 participants	—

SECONDARY outcome

Timeframe: During treatment and every 6 months until 3 years from registration or progression.

Population: None of the Phase I participants were used for this primary endpoint. All 65 Phase II participants were evaluable for this endpoint.

Adverse events (AE) that are classified as either possibly, probably, or definitely related to study treatment according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE version 3.0). The maximum grade for each type of AE will be recorded for each patient. The number of participants with grade 3 or higher adverse events at least possibly related to study treatment are reported here.

Outcome measures

Outcome measures
Measure	Phase I n=65 Participants Participants were accrued to the Phase I portion of this study in each of the 2.5, 3.0, and 3.5 mg dose cohorts to determine the Maximum Tolerated Dose (MTD). Dose limiting Toxicities (DLT) were observed at the 3.5 mg level, and the 3 mg level was confirmed as the maximum tolerated dose. For this study a DLT was defined as a grade 4 hematologic toxicity, a grade 3 or higher febrile neutropenia, or a grade 3 or higher non-hematologic toxicity.	Phase II All patients enrolled to this phase II arm started treatment at 0.5mg/day with CC-4047 every day of each 28 day cycle.
Number of Participants With Treatment Related Adverse Events. Grade 3 or Higher	6 participants	—
Number of Participants With Treatment Related Adverse Events. Grade 4 or Higher	3 participants	—
Number of Participants With Treatment Related Adverse Events. Grade 5	0 participants	—

SECONDARY outcome

Timeframe: Time from response to disease progression, intolerance of study drug, or death.

Population: None of the Phase I participants were evaluable for this endpoint. Sixty-five (65) participants were recruited for the Phase II portion. Results presented here are on the 9 Phase II patients who responded to treatment.

Duration of response is defined as the date at which the patient's objective status is first noted to be a CR, PR or CI to the date progression is documented (if one has occurred) or to the date of last follow-up(for those patients who have not progressed).

Outcome measures

Outcome measures
Measure	Phase I n=9 Participants Participants were accrued to the Phase I portion of this study in each of the 2.5, 3.0, and 3.5 mg dose cohorts to determine the Maximum Tolerated Dose (MTD). Dose limiting Toxicities (DLT) were observed at the 3.5 mg level, and the 3 mg level was confirmed as the maximum tolerated dose. For this study a DLT was defined as a grade 4 hematologic toxicity, a grade 3 or higher febrile neutropenia, or a grade 3 or higher non-hematologic toxicity.	Phase II All patients enrolled to this phase II arm started treatment at 0.5mg/day with CC-4047 every day of each 28 day cycle.
Duration of Response Time	5.6 Months Interval 1.9 to 13.8	—

SECONDARY outcome

Timeframe: Time from registration to the first date of response within twelve 28-day cycles of treatment.

Population: None of the Phase I participants were evaluable for this endpoint. Sixty-five (65) patients were recruited for the Phase II portion. Only 9 of the 65 patients achieved a response. Thus, the median of time to response and the upper limit of 95% confidence interval are not attainable.

The time to response is defined as the time from study registration to the first date at which the patient's objective status was classified as a response (CR, PR or CI). In patients who do not achieve a response, time to response will be censored at the patient's last evaluation date. The distribution for each of these event-time variables (duration of response and time to response) will be estimated by Kaplan-Meier curves.

Outcome measures

Outcome data not reported

Adverse Events

Phase II

Serious events: 19 serious events

Other events: 65 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Phase II n=65 participants at risk All patients enrolled to this Phase II arm started treatment at 0.5mg/day with CC-4047 every day of each 28 day cycle.
Blood and lymphatic system disorders Hemoglobin decreased	3.1% 2/65 • Number of events 2 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Cardiac disorders Myocardial ischemia	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Gastrointestinal disorders Diarrhea	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Gastrointestinal disorders Esophageal varices hemorrhage	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Gastrointestinal disorders Gastrointestinal disorder	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Gastrointestinal disorders Lower gastrointestinal hemorrhage	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
General disorders Edema limbs	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
General disorders Fatigue	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
General disorders Multi-organ failure	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Immune system disorders Hypersensitivity	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Infections and infestations Infectious meningitis	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Infections and infestations Pneumonia	6.2% 4/65 • Number of events 4 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Infections and infestations Upper respiratory infection	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Investigations Leukocyte count decreased	3.1% 2/65 • Number of events 2 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Investigations Neutrophil count decreased	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Investigations Platelet count decreased	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Metabolism and nutrition disorders Tumor lysis syndrome	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Respiratory, thoracic and mediastinal disorders Laryngeal edema	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Skin and subcutaneous tissue disorders Skin ulceration	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Vascular disorders Hematoma	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.

Other adverse events

Other adverse events
Measure	Phase II n=65 participants at risk All patients enrolled to this Phase II arm started treatment at 0.5mg/day with CC-4047 every day of each 28 day cycle.
Blood and lymphatic system disorders Hemoglobin decreased	81.5% 53/65 • Number of events 214 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Cardiac disorders Left ventricular dysfunction	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Endocrine disorders Hypothyroidism	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Gastrointestinal disorders Constipation	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Gastrointestinal disorders Diarrhea	15.4% 10/65 • Number of events 19 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Gastrointestinal disorders Nausea	13.8% 9/65 • Number of events 16 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Gastrointestinal disorders Vomiting	4.6% 3/65 • Number of events 4 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
General disorders Edema limbs	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
General disorders Fatigue	100.0% 65/65 • Number of events 477 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
General disorders Localized edema	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
General disorders Pain	3.1% 2/65 • Number of events 2 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Immune system disorders Hypersensitivity	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Infections and infestations Skin infection	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Investigations Alkaline phosphatase increased	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Investigations Leukocyte count decreased	23.1% 15/65 • Number of events 54 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Investigations Neutrophil count decreased	41.5% 27/65 • Number of events 196 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Investigations Platelet count decreased	66.2% 43/65 • Number of events 274 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Metabolism and nutrition disorders Blood uric acid increased	10.8% 7/65 • Number of events 11 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Metabolism and nutrition disorders Serum potassium increased	3.1% 2/65 • Number of events 3 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Metabolism and nutrition disorders Serum sodium decreased	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Musculoskeletal and connective tissue disorders Joint effusion	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Musculoskeletal and connective tissue disorders Pain in extremity	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Nervous system disorders Peripheral sensory neuropathy	27.7% 18/65 • Number of events 81 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Renal and urinary disorders Hemorrhage urinary tract	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Renal and urinary disorders Protein urine positive	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Renal and urinary disorders Renal failure	3.1% 2/65 • Number of events 2 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Skin and subcutaneous tissue disorders Pruritus	30.8% 20/65 • Number of events 36 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.
Skin and subcutaneous tissue disorders Skin ulceration	1.5% 1/65 • Number of events 1 • Every 28 day cycle while on treatment (up to 12 cycles). The primary endpoint for the Phase I cohort of participants was to determine the MTD based on the frequency of DLTs at increasing dose levels. The adverse events in the Phase I cohort were summarized as the Phase I primary endpoint. Here, we report adverse events of all 65 Phase II participants.

Additional Information

Ayalew Tefferi, M.D.

Mayo Clinic

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place