Trial Outcomes & Findings for Vosaroxin for Intermediate 2 or High-risk MDS After Failure With Hypomethylating Agent-based Therapy (NCT NCT01980056)

NCT ID: NCT01980056

Last Updated: 2019-02-19

Results Overview

Maximum tolerated dose of vosaroxin for short IV infusion in INT-2 or high-risk MDS

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 10 participants
• Primary outcome timeframe: 1 year
• Results posted on: 2019-02-19

Participant Flow

Participant milestones

Measure	Vosaroxin: All Patients Receiving Dose Level 1: Vosaroxin 50 m All patients will receive vosaroxin according to the dose cohort in which they are enrolled. Vosaroxin: Dose level 1: Vosaroxin 50 mg/m\^2 IV on Days 1 and 4 of 28 day cycle	Dose Level 2: Vosaroxin 72 mg/m^2 IV on Days 1 and 4 of 28 Day All patient receiving Dose level 2: Vosaroxin 72 mg/m\^2 IV on Days 1 and 4 of 28 day cycle	Dose Level 3: Vosaroxin 50 mg/m^2 IV on Days 1, 4, 8 and 11 of All patient receiving Dose level 3: Vosaroxin 50 mg/m\^2 IV on Days 1, 4, 8 and 11 of 28 day cycle
Overall Study STARTED	4	4	2
Overall Study COMPLETED	3	3	2
Overall Study NOT COMPLETED	1	1	0

Reasons for withdrawal

Measure	Vosaroxin: All Patients Receiving Dose Level 1: Vosaroxin 50 m All patients will receive vosaroxin according to the dose cohort in which they are enrolled. Vosaroxin: Dose level 1: Vosaroxin 50 mg/m\^2 IV on Days 1 and 4 of 28 day cycle	Dose Level 2: Vosaroxin 72 mg/m^2 IV on Days 1 and 4 of 28 Day All patient receiving Dose level 2: Vosaroxin 72 mg/m\^2 IV on Days 1 and 4 of 28 day cycle	Dose Level 3: Vosaroxin 50 mg/m^2 IV on Days 1, 4, 8 and 11 of All patient receiving Dose level 3: Vosaroxin 50 mg/m\^2 IV on Days 1, 4, 8 and 11 of 28 day cycle
Overall Study Death	1	1	0

Baseline Characteristics

Vosaroxin for Intermediate 2 or High-risk MDS After Failure With Hypomethylating Agent-based Therapy

Baseline characteristics by cohort

Measure	Dose Level 1: Vosaroxin 50 mg/m^2 IV on Days 1 and 4 of 28 Day n=4 Participants All patients will receive vosaroxin according to the dose cohort in which they are enrolled. Vosaroxin: Dose level 1: Vosaroxin 50 mg\^m2 IV on Days 1 and 4 of 28 day cycle	Dose Level 2: Vosaroxin 72 mg/m^2 IV on Days 1 and 4 of 28 Day n=4 Participants All patients will receive vosaroxin according to the dose cohort in which they are enrolled. Dose level 2: Vosaroxin 72 mg\^m2 IV on Days 1 and 4 of 28 day cycle	Dose Level 3: Vosaroxin 50mg/m^2 IV on Days 1, 4, 8 and 11 of n=2 Participants All patients will receive vosaroxin according to the dose cohort in which they are enrolled. Dose level 3: Vosaroxin 50 mg\^m2 IV on Days 1, 4, 8 and 11 of 28 day cycle	Total n=10 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	10 Participants n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized White	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Unknown or not reported	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Region of Enrollment United States	4 participants n=5 Participants	4 participants n=7 Participants	2 participants n=5 Participants	10 participants n=4 Participants

PRIMARY outcome

Timeframe: 1 year

Population: All participants who received at least one dose of Vosaroxin were assessed for DLT in the first cycle of therapy. For this study. MTD is defined as the highest dose level at which no more than 33% of the patients observed at a given dose level experience a DLT.

Maximum tolerated dose of vosaroxin for short IV infusion in INT-2 or high-risk MDS

Outcome measures

Measure	All Study Participants n=10 Participants All patients will receive vosaroxin according to the dose cohort in which they are enrolled. Dose level 1: Vosaroxin 50 mg/m\^2 IV on Days 1 and 4 of 28 day cycle Dose level 2: Vosaroxin 72 mg/m\^2 IV on Days 1 and 4 of 28 day cycle Dose level 3: Vosaroxin 50 mg/m\^2 IV on Days 1, 4, 8 and 11 of 28 day cycle	Dose Level 2: Vosaroxin 72 mg/m^2 IV on Days 1 and 4 of 28 Day Dose level 2: Vosaroxin 72 mg/m\^2 IV on Days 1 and 4 of 28 day cycle	Dose Level 3: Vosaroxin 50 mg/m^2 IV on Days 1, 4, 8 and 11 of Dose level 3: Vosaroxin 50 mg/m\^2 IV on Days 1, 4, 8 and 11 of 28 day cycle
Dosage Determination for IV-infusion of Vosaroxin in Int-2 or High-risk Mds	200 mg/m^2	—	—

SECONDARY outcome

Timeframe: 15 months

Evaluate the clinical activity of vosaroxin in MDS subjects by observing number of patients who achieve complete remission.

Outcome measures

Measure	All Study Participants n=4 Participants All patients will receive vosaroxin according to the dose cohort in which they are enrolled. Dose level 1: Vosaroxin 50 mg/m\^2 IV on Days 1 and 4 of 28 day cycle Dose level 2: Vosaroxin 72 mg/m\^2 IV on Days 1 and 4 of 28 day cycle Dose level 3: Vosaroxin 50 mg/m\^2 IV on Days 1, 4, 8 and 11 of 28 day cycle	Dose Level 2: Vosaroxin 72 mg/m^2 IV on Days 1 and 4 of 28 Day n=4 Participants Dose level 2: Vosaroxin 72 mg/m\^2 IV on Days 1 and 4 of 28 day cycle	Dose Level 3: Vosaroxin 50 mg/m^2 IV on Days 1, 4, 8 and 11 of n=2 Participants Dose level 3: Vosaroxin 50 mg/m\^2 IV on Days 1, 4, 8 and 11 of 28 day cycle
Number of Subjects Who Experience a Response	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 15 months

Characterize the blood product transfusion requirements in this patient population when treated with vosaroxin

Outcome measures

Measure	All Study Participants n=4 Participants All patients will receive vosaroxin according to the dose cohort in which they are enrolled. Dose level 1: Vosaroxin 50 mg/m\^2 IV on Days 1 and 4 of 28 day cycle Dose level 2: Vosaroxin 72 mg/m\^2 IV on Days 1 and 4 of 28 day cycle Dose level 3: Vosaroxin 50 mg/m\^2 IV on Days 1, 4, 8 and 11 of 28 day cycle	Dose Level 2: Vosaroxin 72 mg/m^2 IV on Days 1 and 4 of 28 Day n=4 Participants Dose level 2: Vosaroxin 72 mg/m\^2 IV on Days 1 and 4 of 28 day cycle	Dose Level 3: Vosaroxin 50 mg/m^2 IV on Days 1, 4, 8 and 11 of n=2 Participants Dose level 3: Vosaroxin 50 mg/m\^2 IV on Days 1, 4, 8 and 11 of 28 day cycle
Number of Transfusions Required During Treatment With Vosaroxin	19.8 Transfusions Interval 2.0 to 44.0	22.5 Transfusions Interval 12.0 to 33.0	22 Transfusions Interval 17.0 to 27.0

Adverse Events

Dose Level 1: Vosaroxin 50 mg/m2 IV on Days 1 and 4 of 28 Day

Serious events: 3 serious events

Other events: 3 other events

Deaths: 1 deaths

Dose Level 2: Vosaroxin 72 mg/m2 IV on Days 1 and 4 of 28 Day

Serious events: 1 serious events

Other events: 3 other events

Deaths: 1 deaths

Dose Level 3: Vosaroxin 50 mg/m2 IV on Days 1, 4, 8 and 11 of

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Dose Level 1: Vosaroxin 50 mg/m2 IV on Days 1 and 4 of 28 Day n=4 participants at risk Vosaroxin: Dose level 1: Vosaroxin 50 mg/m2 IV on Days 1 and 4 of 28 day cycle	Dose Level 2: Vosaroxin 72 mg/m2 IV on Days 1 and 4 of 28 Day n=4 participants at risk Dose level 2: Vosaroxin 72 mg/m2 IV on Days 1 and 4 of 28 day cycle	Dose Level 3: Vosaroxin 50 mg/m2 IV on Days 1, 4, 8 and 11 of n=2 participants at risk Dose level 3: Vosaroxin 50 mg/m2 IV on Days 1, 4, 8 and 11 of 28 day cycle
Blood and lymphatic system disorders Febrile Neutropenia	75.0% 3/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	0.00% 0/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	50.0% 1/2 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.
General disorders Non- Cardiogenic Shock	0.00% 0/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	25.0% 1/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	0.00% 0/2 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.
General disorders Sudden Death	25.0% 1/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	0.00% 0/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	0.00% 0/2 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.
Respiratory, thoracic and mediastinal disorders Respiratory Distress	25.0% 1/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	0.00% 0/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	0.00% 0/2 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.
Blood and lymphatic system disorders Disease Progression	0.00% 0/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	0.00% 0/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	50.0% 1/2 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.

Other adverse events

Measure	Dose Level 1: Vosaroxin 50 mg/m2 IV on Days 1 and 4 of 28 Day n=4 participants at risk Vosaroxin: Dose level 1: Vosaroxin 50 mg/m2 IV on Days 1 and 4 of 28 day cycle	Dose Level 2: Vosaroxin 72 mg/m2 IV on Days 1 and 4 of 28 Day n=4 participants at risk Dose level 2: Vosaroxin 72 mg/m2 IV on Days 1 and 4 of 28 day cycle	Dose Level 3: Vosaroxin 50 mg/m2 IV on Days 1, 4, 8 and 11 of n=2 participants at risk Dose level 3: Vosaroxin 50 mg/m2 IV on Days 1, 4, 8 and 11 of 28 day cycle
Gastrointestinal disorders Diarrhea	50.0% 2/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	50.0% 2/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	100.0% 2/2 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.
General disorders Fatigue	75.0% 3/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	25.0% 1/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	50.0% 1/2 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.
Blood and lymphatic system disorders Febrile Neutropenia	75.0% 3/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	25.0% 1/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	50.0% 1/2 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.
Gastrointestinal disorders Constipation	75.0% 3/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	25.0% 1/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	0.00% 0/2 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.
Infections and infestations Oral Thrush	25.0% 1/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	25.0% 1/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	0.00% 0/2 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.
General disorders Epistaxis	50.0% 2/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	25.0% 1/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	50.0% 1/2 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.
Gastrointestinal disorders Nausea	50.0% 2/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	75.0% 3/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	50.0% 1/2 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.
Gastrointestinal disorders Vomiting	25.0% 1/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	50.0% 2/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	0.00% 0/2 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.
Gastrointestinal disorders Mucositis	25.0% 1/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	25.0% 1/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	100.0% 2/2 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.
Infections and infestations Bacterimia	0.00% 0/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	25.0% 1/4 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.	100.0% 2/2 • Adverse events were collected over a period of 15 months. The adverse events and SAEs were assessed and graded by the principal investigator throughout the study.

Additional Information

Clinical Trials Administrator

Weill Cornell Medicine

Phone: 212-746-0284

Email: ray2013@med.cornell.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place