Myelodysplastic SyndromePhase 2IST-CTI-MDSNCT02452346
Study of Clinical Efficacy and Safety of Tosedostat in MDS
A Phase 2 study testing Tosedostat in people with Myelodysplastic Syndrome, run by Weill Medical College of Cornell University at 1 site in United States.
Trial summary
Study WCMC IST-CTI-MDS evaluates the safety and tolerability of tosedostat in adult patients with pathologically confirmed MDS (< 20% blasts in bone marrow, peripheral blood, or both) by World Health Organization (WHO) classification after failure of hypomethylating agent-based therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome
- What is being tested?
- Tosedostat
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Mar 2015to 25 Oct 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Able to understand and to provide written informed consent
- At least 18 years of age with pathologically confirmed MDS (<20% blasts in bone marrow, peripheral blood, or both) within 6 weeks prior to screening by WHO classification
- Must have received at least 4 cycles of decitabine-based or 6 cycles of azacitidine-based therapy and are either refractory to, relapsed after or intolerant to prior therapy with either agent.
- Primary failure/refractory: Stable or worsening disease after a minimum of 4 cycles of decitabine-based or 6 cycles of azacitidine-based therapy
- Secondary failure/relapse: Bone marrow blast count increase or loss of hematologic response after initial treatment response with hypomethylating agent-based therapy
- Intolerance: Intolerance of hypomethylating agent-based therapy regardless of number of cycles completed and clinical response
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- Progression (according to 2006 IWG criteria) at any time after initiation of subcutaneous or intravenous azacitidine or decitabine treatment per labeling during the past 2 years, defined as follows:
- For patients with <5% BMBL, ≥ 50% increase in BMBL to >5% BMBL
- For patients with 5-10% BMBL, ≥ 50% increase in BMBL to >10% BMBL
- For patients with 10-20% BMBL, ≥ 50% increase in BMBL to >20% BMBL
- For patients with 20-30% BMBL, ≥ 50% increase in BMBL to >30% BMBL
- Any of the following:
- ≥ 50% decrease from maximum remission/response levels in granulocytes or PLT
- Decrease in Hgb concentration by ≥2 g/dL
- Transfusion dependence, defined as administration of at least 4 RBC units in the past 8 weeks before Screening (patients must have Hgb values < 9 g/dL prior to transfusion to be considered), in the absence of another explanation.
- Has failed to respond to, relapsed following, not eligible, or opted not to participate in BM transplantation
- Patients with very low, low or intermediate risk MDS by the IPSS-R must be transfusion-dependent, with a packed red blood cell requirement of ≥ 2 units/month
- Off azacitidine or decitabine for at least 2 weeks, off all other treatments for MDS for at least 4 weeks. Filgrastim (G-CSF) and EPO are allowed before and during the study as clinically indicated
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
- Subjects must have adequate hepatic and renal function including the following:
- Total bilirubin ≤ 1.5 x upper limit of normal (in the absence of Gilbert's syndrome)
- AST and ALT ≤ 2.5 x upper limit of normal
- Serum creatinine ≤ 1.5 x upper limit of normal
- Must have acceptable recovery from clinically significant non-hematologic toxicity after prior therapy.
- Must have a life expectancy of at least 2 months
- Screening left ventricular ejection fraction (LVEF) greater than 50% as documented by transthoracic echocardiogram (TTE)
- Female subject of child-bearing potential and male subjects with female partners of reproductive potential must use acceptable contraceptive methods (hormonal or barrier method of birth control; abstinence) for the duration of time on study and continue to do so for a further 3 months after the end of tosedostat treatment. Should a female subject become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Able to comply with all study procedures during the study including all visits and tests
- Willing to adhere to the prohibitions and restrictions specified in this protocol
- Patient must sign an informed consent form (ICF) indicating that s/he understands the purpose of and procedures required for the study and is willing to participate.
Who cannot join
- Presence of AML (≥20% blasts in bone marrow, peripheral blood, or both)
- Presence of serious illness, medical condition, or other medical history, involving the heart, kidney, liver, or other organ system, including abnormal laboratory parameters, which, in the opinion of the Investigator, would be likely to interfere with a subject's participation in the study or with the interpretation of the results.
- Have known active central nervous system disease or active, uncontrolled, clinically significant infection(s)
- Have other active malignancies (including other hematologic malignancies) or other malignancies within 12 months before enrollment, except non-melanoma skin cancer or cervical intraepithelial neoplasia
- Are receiving any other investigational therapy or protocol-prohibited therapy
- Have received previous treatment with tosedostat
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- Pregnant or breastfeeding females
- Any prior or co-existing medical condition that in the Investigator's judgment will substantially increase the risk associated with the subject's participation in the study
- Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
- Significant* cardiovascular disease defined as:
- Active heart disease including myocardial infarction within 6 months prior to study entry
- Symptomatic coronary artery disease
- Uncontrolled or clinically significant arrhythmia, angina, congestive heart failure
- Presence of clinically significant valvular heart disease
- Presence of clinically significant conduction defect on screening ECG
- Uncontrolled hypertension (i.e., systolic BP >160mmHg, diastolic >90 mmHg in repeated measurements) despite adequate therapy
- Clinically significant atrial fibrillation * Grade 3/4 in the CTCAE v4.0 grading would generally be considered clinically significant, although this remains a judgment for the Investigator to make.
- LVEF ≤ 50%
- Baseline troponin I and b-type natriuretic peptide > Grade I
- Prior exposure cardiotoxic agent, such as anthracycline, within 3 months of enrollment
- Concomitant use of drugs that prolong QT/QTc interval except antibiotics, antifungals, and other antimicrobials used as standard of care for the treatment and prevention of infection and/or other such drugs clinically indicated for patient care. When use of concomitant medications with QT-prolonging potential is necessary, ECG must be repeated 4 hours post-dose on Day 1, on Day 3, and on Day 7, and as clinically indicated, relative to start of agent with QT-prolonging potential.
- Gastrointestinal disorders that may interfere with absorption of drug
- Active serious infection or sepsis
- Clinically significant interstitial lung disease
Trial locations and contacts
1 site in 1 country.
United States1 site
Weill Cornell Medical College
New York, New York, 10065
About this study
Official title: Phase II Clinical Study of the Clinical Efficacy and Safety of Tosedostat in Atients With Myelodysplastic Syndromes (MDS) After Failure of Hypomethylating Agent-Based Therapy
Study WCMC IST-CTI-MDS evaluates the safety and tolerability of tosedostat in adult patients with pathologically confirmed MDS (< 20% blasts in bone marrow, peripheral blood, or both) by World Health Organization (WHO) classification after failure of hypomethylating agent-based therapy.
Read the detailed description
This is a single-center, open label, two-arm phase II study of clinical activity of tosedostat in adult patients with MDS who have failed prior hypomethylating agent-based therapy. Arm A is defined as Revised International Prognostic Scoring Systems (IPSS-R) very low, low, and intermediate disease. Arm B is defined as IPSS-R high or very high risk disease. The two arms are separate and will enroll simultaneously. The dose of tosedostat will be 120 mg once a day continuously for each 28 day treatment cycle. Patients will be assessed for disease response, on average, every two cycles as defined in the protocol. If patient has no response as defined by the protocol after two cycles, azacitidine 75 mg/m2 SC or IV for 5 days may be combined with tosedostat, at the investigator's discretion.The primary endpoint the study is to evaluate the safety and efficacy of tosedostat in two groups of patients with myelodysplastic syndrome who have relapsed after or are refractory or intolerant to azacitidine or decitabine. The primary endpoint for patients with IPSS-R very low, low and intermediate disease is transfusion independence and the primary endpoint for patients with high or very high risk disease is overall survival.
- Conditions
- Myelodysplastic Syndrome
- Being tested
- Tosedostat
- Keywords
- MDS
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TosedostatDrug
Also called CHR-2797
120 mg PO once daily continuously for each 28 day treatment cycle
| Study group | Role | What they receive |
|---|---|---|
| All Patients | Experimental | Tosedostat 120 mg PO once daily will be administered. Receives: Drug: Tosedostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Over All Survival
Survival following treatment to the date of death, assessed up to a period of 3-4 years.
Measured: from start of treatment until death, assessed up to a period of 3-4 years.
Secondary outcomes (2)
Overall Response
Overall response according to IWG 2006 criteira
Measured: Approximately 3 years
One Year and Two Year Survival
Measured: from start of treatment to 1 year and 2 years post treatment initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2015 (estimated)
- Study start20 Mar 2015
- Primary completion25 Oct 2017
- Study completion25 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- CTI BioPharma
- Responsible party
- Sponsor
- Investigators
- Gail Roboz, MD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02452346
- Sponsor's protocol ID
- 1409015482
- Acronym
- IST-CTI-MDS
- Status last verified
- Jun 2018
- First submitted
- 28 Jan 2015
- Last updated
- 12 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Lee S, Desai P, Edirisinghe B, Pianello S, Curcio T, Samuel M, Ritchie EK, Roboz GJ. Phase II study of the clinical efficacy and safety of tosedostat in patients with myelodysplastic syndromes (MDS) after failure of hypomethylating agent-based therapy. Leuk Lymphoma. 2021 Feb;62(2):498-500. doi: 10.1080/10428194.2020.1832674. Epub 2020 Oct 10. No abstract available.
PubMed 33043735
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Clinical Study of the Clinical Efficacy and Safety of Tosedostat in Atients With Myelodysplastic Syndromes (MDS) After Failure of Hypomethylating Agent-Based Therapy
- ClinicalTrials.gov ID
- NCT02452346
- Acronym / sponsor ID
- IST-CTI-MDS / 1409015482
- Conditions
- Myelodysplastic Syndrome
- Keywords
- MDS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- CTI BioPharma
- Study start
- 20 Mar 2015 (actual)
- Primary completion
- 25 Oct 2017 (actual)
- Study completion
- 25 Oct 2017 (actual)
- First posted
- 22 May 2015 (estimated)
- Results
- Posted 12 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study WCMC IST-CTI-MDS evaluates the safety and tolerability of tosedostat in adult patients with pathologically confirmed MDS (< 20% blasts in bone marrow, peripheral blood, or both) by World Health Organization (WHO) classification after failure of hypomethylating agent-based therapy.
Detailed description
This is a single-center, open label, two-arm phase II study of clinical activity of tosedostat in adult patients with MDS who have failed prior hypomethylating agent-based therapy. Arm A is defined as Revised International Prognostic Scoring Systems (IPSS-R) very low, low, and intermediate disease. Arm B is defined as IPSS-R high or very high risk disease. The two arms are separate and will enroll simultaneously. The dose of tosedostat will be 120 mg once a day continuously for each 28 day treatment cycle. Patients will be assessed for disease response, on average, every two cycles as defined in the protocol. If patient has no response as defined by the protocol after two cycles, azacitidine 75 mg/m2 SC or IV for 5 days may be combined with tosedostat, at the investigator's discretion.The primary endpoint the study is to evaluate the safety and efficacy of tosedostat in two groups of patients with myelodysplastic syndrome who have relapsed after or are refractory or intolerant to azacitidine or decitabine. The primary endpoint for patients with IPSS-R very low, low and intermediate disease is transfusion independence and the primary endpoint for patients with high or very high risk disease is overall survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All Patients | Experimental | Drug: TosedostatTosedostat 120 mg PO once daily will be administered. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- Able to understand and to provide written informed consent
- At least 18 years of age with pathologically confirmed MDS (<20% blasts in bone marrow, peripheral blood, or both) within 6 weeks prior to screening by WHO classification
- Must have received at least 4 cycles of decitabine-based or 6 cycles of azacitidine-based therapy and are either refractory to, relapsed after or intolerant to prior therapy with either agent.
- Progression (according to 2006 IWG criteria) at any time after initiation of subcutaneous or intravenous azacitidine or decitabine treatment per labeling during the past 2 years, defined as follows:
- Has failed to respond to, relapsed following, not eligible, or opted not to participate in BM transplantation
Key exclusion criteria (24 listed)
- Presence of AML (≥20% blasts in bone marrow, peripheral blood, or both)
- Presence of serious illness, medical condition, or other medical history, involving the heart, kidney, liver, or other organ system, including abnormal laboratory parameters, which, in the opinion of the Investigator, would be likely to interfere with a subject's participation in the study or with the interpretation of the results.
- Have known active central nervous system disease or active, uncontrolled, clinically significant infection(s)
- Have other active malignancies (including other hematologic malignancies) or other malignancies within 12 months before enrollment, except non-melanoma skin cancer or cervical intraepithelial neoplasia
- Are receiving any other investigational therapy or protocol-prohibited therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TosedostatAlso: CHR-2797120 mg PO once daily continuously for each 28 day treatment cycle | Drug | All Patients |
Primary outcome
Over All Survival
Time frame: from start of treatment until death, assessed up to a period of 3-4 years.
Survival following treatment to the date of death, assessed up to a period of 3-4 years.
2 secondary outcomes
Overall Response
Time frame: Approximately 3 years
One Year and Two Year Survival
Time frame: from start of treatment to 1 year and 2 years post treatment initiation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33043735Lee S, Desai P, Edirisinghe B, Pianello S, Curcio T, Samuel M, Ritchie EK, Roboz GJ. Phase II study of the clinical efficacy and safety of tosedostat in patients with myelodysplastic syndromes (MDS) after failure of hypomethylating agent-based therapy. Leuk Lymphoma. 2021 Feb;62(2):498-500. doi: 10.1080/10428194.2020.1832674. Epub 2020 Oct 10. No abstract available.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gail Roboz, MD principal investigator
Weill Medical College of Cornell University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tosedostat in people with Myelodysplastic Syndrome, run by Weill Medical College of Cornell University at 1 site 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 30 inclusion and 24 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 12 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Over All Survival (time frame: from start of treatment until death, assessed up to a period of 3-4 years.). 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 NCT02452346, which also lists 1 linked publication.
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 12 Jun 2018.