Dose Escalation and Proof-of-Concept Studies of Vactosertib (TEW-7197) Monotherapy in Patients With MDS

NCT03074006 | Completed Phase 1 FDA Drug

• 1 other identifier: MP-MDS-01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 3

Brief Summary

This is a prospective, open-label, multicenter, phase 1/2 study of TEW-7197 in patients with low and intermediate risk of myelodysplastic syndrome (MDS).

Conditions

Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) for dose escalation phase

  To define the MTD and determine RP2D

  4 weeks

• Hematologic improvement (HI)

  To evaluate the best hematologic improvement (HI) based on IWG 2006 criteria

  At 2, 4, 8, 12 and 16 weeks of treatment

Secondary Outcomes (8)

• Hematologic Improvement (HI)

  At 2, 4, 8, 12 and 16 weeks of treatment

• Red blood cell transfusion independency

  At 2, 4, 8, 12 and 16 weeks of treatment

• Bone marrow response and cytogenetic response

  At 2, 4, 8, 12 and 16 weeks of treatment

• Time to progression

  At 2, 4, 8, 12 and 16 weeks of treatment

• Relationship between mutations and response

  At 2, 4, 8, 12 and 16 weeks of treatment

Study Arms (2)

low dose

EXPERIMENTAL

Drug: TEW-7197

high dose

EXPERIMENTAL

Drug: TEW-7197

Interventions

TEW-7197 DRUG

50mg tablets (doses will be determined through dose-escalation part)

high dose; low dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects are eligible to be included in the study only if they meet all of the following criteria:
• Subjects who are males or females ≥ 18 years of age.
• Subjects who are able to give written informed consent.
• Subjects who have a documented diagnosis of MDS according to WHO criteria.
• Subjects who have Revised International Prognostic Scoring System (IPSS-R) categories of Very Low, Low- or Intermediate-risk disease. Subjects with cytogenetic failure and ≤ 10% marrow blasts will be eligible.
• Subjects who meet one of the following hematologic criteria within 8 weeks of registration (according to the IWG criteria) and as documented in prior transfusion logs or weekly hematology evaluations:
• Symptomatic anemia untransfused with hemoglobin ≤ 9.0 g/dL or with RBC transfusion-dependence (i.e., ≥ 2 units/month) confirmed for a minimum of 8 weeks before randomization.
• Platelet counts of \< 100 x109/L
• Absolute neutrophil count \< 1500
• Subjects with del(5q) who should have failed or not be a candidate for approved therapy (Lenalidomide) prior to enrolling on this study.
• Subjects must meet accepted standard criteria for treatment and have failed or not be candidates for standard, accepted treatments.
• Subjects who have sufficient hepatic function, defined as bilirubin 2 times the upper limit of normal (ULN) and alanine transaminase (ALT) and aspartate transaminase (AST) levels 2.5 times ULN.
• Subjects who have sufficient renal function, defined as serum creatinine levels 1.5 ULN.
• Subjects who have a performance status of 2 on the Eastern Cooperative Oncology Group (ECOG) scale (refer to Appendix 2).
• Subjects who have discontinued all previous therapies for MDS or other investigational therapy for at least 28 days prior to study enrollment and recovered to less than grade 2 toxicity from prior therapy.

You may not qualify if:

• Subjects will be excluded from the study if they meet any of the following criteria:
• Subjects who have received treatment within the last 28 days with a drug that has not received regulatory approval for any indication at the time of study entry.
• Subjects who have moderate or severe cardiac disease:
• Subjects who have the presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association (NYHA) Class III/IV congestive heart failure, or uncontrolled hypertension.
• Subjects who have documented major electrocardiogram (ECG) abnormalities at the investigator's discretion (for example, symptomatic or sustained atrial or ventricular arrhythmias, second- or third-degree atrioventricular block, bundle branch blocks, ventricular hypertrophy, or recent myocardial infarction).
• Subjects who have major abnormalities documented by echocardiography with Doppler (for example, moderate or severe heart valve function defect and/or left ventricular ejection fraction (LVEF) \<50%, evaluation based on the institutional lower limit of normal).
• Subjects who have predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan-Syndrome, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by CT scan with contrast).
• Subjects who have documented iron, B12, folate deficiency as determined by the investigator.
• Female subjects who are breastfeeding, or intend to breastfeed during the duration of the study and for 30 days following the last dose of study drug.
• Subjects with any other serious medical condition which in the Investigator's opinion would preclude safe participation in the study.
• Subjects, in the opinion of the Investigator, who are unsuitable to participate in the study.
• Subjects with elevated Troponin 1 levels at screening or known to have persistently elevated brain natriuretic peptide (BNP).
• Subjects with serious pre-existing medical conditions as follows:
• History of cardiac or aortic surgery,
• Hypertension that is not controlled by standard medication (to 150/90 mmHg or below),

Sponsors & Collaborators

• MedPacto, Inc.: lead

Study Sites (3)

Site 03

Tampa, Florida, 33612, United States

Location

Site 02

Baltimore, Maryland, 21201, United States

Location

Site 01

The Bronx, New York, 10461, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Sunjin Hwang, MD

  MedPacto, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2017
• First Posted: March 8, 2017
• Study Start: January 4, 2018
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: September 28, 2021

Record last verified: 2021-06

Locations

US (3)