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Myelodysplastic SyndromesPhase 1NCT03074006

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

A Phase 1 study testing TEW-7197 in people with Myelodysplastic Syndromes, run by MedPacto, Inc. at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelodysplastic Syndromes
What is being tested?
TEW-7197
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
3 sitesUnited States
Study dates
4 Jan 2018to 31 Dec 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.
  • Subjects who are able to swallow tablets.
  • Subject who are willing and able to comply with scheduled visits, treatment plans, laboratory tests and procedures.
  • Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days of the first administration of study drug. For the purpose of this study, female subjects of childbearing potential are defined as all female subjects after puberty unless they are postmenopausal for at least 1 year, or are surgically sterile (hysterectomy or bilateral oophorectomy or tubal ligation).
  • Female subjects of child bearing potential who are willing to avoid the pregnancy during the duration of the study and for 30 days following the last dose of study drug. The effects of TEW-7197 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Subjects with QTc interval calculated according to Fridericia's formula (QTcF = QT/RR0.33; RR = RR interval) of ≤ 470 ms for males and 450 ms for females on screening electrocardiogram (ECG).
  • Subjects must have ejection fraction more than 50% and no clinically significant valvular dysfunction.
  • Subjects must have discontinued radiotherapy at least 14 days with resolution of any toxicity to Grade 1 or better prior to the start of treatment.

Who cannot join

  • 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).
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  • 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),
  • Cirrhosis of the liver, Child-Pugh Stage B or C, or history of liver transplant,
  • Severe diabetes that is not currently controlled,
  • Current or history of interstitial pneumonitis,
  • Presence of aneurisms of the ascending aorta or aortic stress.
  • Subjects with known history of difficulty swallowing, malabsorption or other conditions that may reduce absorption of the product.
  • Subjects with major abnormalities identified by ECG or echocardiogram (ECHO), at the Investigator's discretion.
  • Subjects with active infection with human immunodeficiency virus, hepatitis B virus or hepatitis C virus.
  • Subjects with active infection requiring systemic antibiotic therapy.
  • Subjects who are currently using or planning to use:
  • Drugs which are exclusively or primarily eliminated by cytochrome P-450 isozyme 3A4

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Site 02

    Baltimore, Maryland, 21201

  • Site 03

    Tampa, Florida, 33612

  • Site 01

    The Bronx, New York, 10461

Other trials in United States

About this study

Official title: Phase 1/2 Study of Vactosertib (TEW-7197) Monotherapy in Patients With Low or Intermediate Myelodysplastic Syndromes

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).

Being tested
TEW-7197
Medical subject headings
Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TEW-7197Drug

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

Study groups in NCT03074006
Study groupRoleWhat they receive
low doseExperimentalNot described
Receives: Drug: TEW-7197
high doseExperimentalNot described
Receives: Drug: TEW-7197

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) for dose escalation phase

    To define the MTD and determine RP2D

    Measured: 4 weeks

  2. Hematologic improvement (HI)

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

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

Secondary outcomes (8)

  1. Hematologic Improvement (HI)

    To evaluate the duration of HI

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

  2. Red blood cell transfusion independency

    To evaluate rate and duration of Red blood cell transfusion independency

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

  3. Bone marrow response and cytogenetic response

    To evaluate the frequency of bone marrow response (CP+PR) and cytogenetic response

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

  4. Time to progression

    Time to progression to higher risk or acute myeloid leukemia

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

  5. Relationship between mutations and response

    To evaluate the relationship between mutations and response

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

  6. Relationship between various stem and progenitor alterations and response

    To evaluate the relation ship between various stem and progenitor alterations and response

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

  7. Quality of life with MDS

    To evaluate the quality of life parameters experienced by patients with MDS

    Measured: At 4, 8, 12 and 16 weeks of treatment

  8. Biomarker

    Determine pharmacodynamic markers in bone marrow

    Measured: At 4, 8, 12 and 16 weeks of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Mar 2017
  2. Study start4 Jan 2018
  3. Primary completion31 Dec 2019
  4. Study completion31 Dec 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03074006
Sponsor's protocol ID
MP-MDS-01
Status last verified
Jun 2021
First submitted
27 Feb 2017
Last updated
28 Sep 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TEW-7197 in people with Myelodysplastic Syndromes, run by MedPacto, Inc. at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) for dose escalation phase (time frame: 4 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03074006.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2021.

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