Myelodysplastic SyndromesPhase 1NCT03057990
Pyrimethamine for Intermediate/High-risk Myelodysplastic Syndromes (MDS)
A Phase 1 study testing Pyrimethamine in people with Myelodysplastic Syndromes, run by Montefiore Medical Center at 1 site in United States.
Trial summary
This is a phase I study designed to assess the maximum tolerated dose (MTD) of pyrimethamine and provide the recommended Phase 2 dose (RP2D) for the treatment of intermediate/high-risk MDS that is refractory to or relapsed after treatment with azanucleosides. 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?
- Pyrimethamine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Sep 2019to 29 Jun 2021
- 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
- Participants at or above the age of 18 years
- Diagnosis of MDS confirmed within 6 months, by review of patient chart, prior to study entry according to WHO (World Health Organization) criteria or FAB (French-American-British) classification
- MDS classified as intermediate-1, intermediate-2 or high risk as per the International Prognostic Scoring System-Revised (IPSS-R) score with a confirmed diagnosis of MDS with cytogenetic abnormalities at diagnosis and bone marrow blast percentage between 10 and 30 percent (for patients with cytogenetic failure or dry tap)
- Potential participants must meet ONE of the following:
- Progression (according to 2006 International Working Group (IWG) criteria) at any time after initiation of azacitidine or decitabine treatment during the past 3 years; OR
- Failure to achieve complete or partial response or hematological improvement (according to 2006 IWG) after at least four cycles of azacitidine or decitabine administered during the past 3 years OR
Show all 14Show fewer
- Relapse after initial complete or partial response or hematological improvement (according to 2006 IWG criteria) observed after at least four cycles of azacitidine or decitabine administered during the past 3 years OR
- Intolerance to azacitidine or decitabine defined by drug-related more than or equal to Grade 3 liver or renal toxicity leading to treatment discontinuation during the past 3 years
- Off all other treatments for MDS for at least 3 weeks. Filgrastim (G-CSF) and erythropoietin are allowed before and during the study as clinically indicated
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- Willing to adhere to the prohibitions and restrictions specified in this protocol
- Patient (or patient's legally authorized representative) must signed an informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study
- Adequate organ and marrow function as defined in the protocol.
- Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy.
Who cannot join
- Current or anticipated use of other investigational agents
- Participants who have had chemotherapy or radiotherapy within 3 weeks prior to entering the study or those who have not recovered from clinically significant adverse events due to agents administered more than 3 weeks earlier.
- History of allergic reactions or sensitivity to pyrimethamine
- Patients with a history of folic acid deficiency, currently on folic acid replacement therapy or a previous history of megaloblastic anemia thought related to folic acid deficiency
- Current use or anticipated need for treatment with any medications or substances that are inhibitors or inducers of CYP2C9.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant or nursing women
Trial locations and contacts
1 site in 1 country.
United States1 site
Montefiore Medical Center
The Bronx, New York, 10467
About this study
Official title: A Phase 1 Study of Pyrimethamine, a STAT3 Inhibitor, for the Treatment of Intermediate/ High-risk Myelodysplastic Syndromes (MDS) That Has Relapsed or is Refractory to Azanucleosides
This is a phase I study designed to assess the maximum tolerated dose (MTD) of pyrimethamine and provide the recommended Phase 2 dose (RP2D) for the treatment of intermediate/high-risk MDS that is refractory to or relapsed after treatment with azanucleosides.
Read the detailed description
The objective of this study is to determine the safety, dose tolerance, pharmacokinetics and pharmacodynamics of pyrimethamine in intermediate / high-risk / relapsed or azanucleoside-refractory MDS within the confines of a phase I study.
Pyrimethamine self-administered by participants orally once per day in morning with food. Phase 1 study will start at dose of 50 mg once per day. (NOTE: For participants at dose level of 50mg, the dose reduction, if needed is 25 mg.)
Intra-patient dose escalation is permitted (not beyond the highest dose allowed) if Complete Remission/Response (CR) is not reached in week 1 of Cycle 3 and there is no significant toxicity. (NOTE: In this study, the term "intra-patient" indicates within each participant and not between different participants; i.e., dose escalation will be done within each individual participant.) The decision to escalate intra-patient doses will be based on safety and dose tolerance assessments made at the end of one treatment cycle (28 days of continuous drug administration) for all 6 participants. Dose-limiting toxicity (DLT) is defined as the occurrence of two consecutive grade 2 or 3 serious adverse events (SAEs) not recovered within 24 hours at a given dose. MTD will be defined as the dose where no DLT is observed among three consecutive participants, or no more than one DLT among six participants. Participants will be treated initially for one 28-day cycle followed by a toxicity evaluation - Toxicity and adverse effect assessments will be made on Day 1 and Day 28 of every cycle of therapy.
- Conditions
- Myelodysplastic Syndromes
- Being tested
- Pyrimethamine
- Keywords
- Pyrimethamine, Myelodysplastic Syndromes (MDS), Refractory, Relapsed
- Medical subject headings
- Myelodysplastic Syndromes, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PyrimethamineDrug
Also called Daraprim
Pyrimethamine will be administered 50mg/100mg/150mg once daily on days 1-28 of each 28-day cycle. Administered using intra-patient dose escalation, starting at 50 mg and up to 150 mg.
| Study group | Role | What they receive |
|---|---|---|
| Pyrimethamine Treatment (Intra-patient) | Experimental | 50mg/100mg/150mg once daily on days 1-28 of each 28-day cycle. Administered using intra-patient dose escalation, starting at 50 mg and up to 150 mg. Receives: Drug: Pyrimethamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity (DLT)
Determination of DLT to be made at the completion of each cohort.
Measured: Day 28
Maximum tolerated dose (MTD)
The dose where no DLT is observed among 3 consecutive participants, or no more than one DLT among 6 participants.
Measured: up to 28 days
Recommended Phase II Dose (RPTD, RP2D)
Pyrimethamine will be dose-escalated until the largest dose is reached that is determined to be safe based on adverse event reporting and dose-limiting toxicity information from all participants.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2017
- Study start11 Sep 2019
- Primary completion29 Jun 2021
- Study completion29 Jun 2021
Why it stopped: Study never opened; closed on 06/29/2021 due to no enrllment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by Montefiore Medical CenterThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Montefiore Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Albert Einstein College of Medicine
- Responsible party
- Sponsor
- Investigators
- Aditi Shastri, MD, Principal investigator, Montefiore Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03057990
- Sponsor's protocol ID
- 2019-10346
- Other IDs
- 2019
- Status last verified
- Sep 2021
- First submitted
- 30 Nov 2016
- Last updated
- 22 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of Pyrimethamine, a STAT3 Inhibitor, for the Treatment of Intermediate/ High-risk Myelodysplastic Syndromes (MDS) That Has Relapsed or is Refractory to Azanucleosides
- ClinicalTrials.gov ID
- NCT03057990
- Acronym / sponsor ID
- 2019-10346
- Conditions
- Myelodysplastic Syndromes
- Keywords
- Pyrimethamine, Myelodysplastic Syndromes (MDS), Refractory, Relapsed
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study never opened; closed on 06/29/2021 due to no enrllment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Montefiore Medical CenterUniversity, hospital or other
- Collaborators
- Albert Einstein College of Medicine
- Study start
- 11 Sep 2019 (actual)
- Primary completion
- 29 Jun 2021 (actual)
- Study completion
- 29 Jun 2021 (actual)
- First posted
- 20 Feb 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase I study designed to assess the maximum tolerated dose (MTD) of pyrimethamine and provide the recommended Phase 2 dose (RP2D) for the treatment of intermediate/high-risk MDS that is refractory to or relapsed after treatment with azanucleosides.
Detailed description
The objective of this study is to determine the safety, dose tolerance, pharmacokinetics and pharmacodynamics of pyrimethamine in intermediate / high-risk / relapsed or azanucleoside-refractory MDS within the confines of a phase I study.
Pyrimethamine self-administered by participants orally once per day in morning with food. Phase 1 study will start at dose of 50 mg once per day. (NOTE: For participants at dose level of 50mg, the dose reduction, if needed is 25 mg.)
Intra-patient dose escalation is permitted (not beyond the highest dose allowed) if Complete Remission/Response (CR) is not reached in week 1 of Cycle 3 and there is no significant toxicity. (NOTE: In this study, the term "intra-patient" indicates within each participant and not between different participants; i.e., dose escalation will be done within each individual participant.) The decision to escalate intra-patient doses will be based on safety and dose tolerance assessments made at the end of one treatment cycle (28 days of continuous drug administration) for all 6 participants. Dose-limiting toxicity (DLT) is defined as the occurrence of two consecutive grade 2 or 3 serious adverse events (SAEs) not recovered within 24 hours at a given dose. MTD will be defined as the dose where no DLT is observed among three consecutive participants, or no more than one DLT among six participants. Participants will be treated initially for one 28-day cycle followed by a toxicity evaluation - Toxicity and adverse effect assessments will be made on Day 1 and Day 28 of every cycle of therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pyrimethamine Treatment (Intra-patient) | Experimental | Drug: Pyrimethamine50mg/100mg/150mg once daily on days 1-28 of each 28-day cycle. Administered using intra-patient dose escalation, starting at 50 mg and up to 150 mg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Participants at or above the age of 18 years
- Diagnosis of MDS confirmed within 6 months, by review of patient chart, prior to study entry according to WHO (World Health Organization) criteria or FAB (French-American-British) classification
- MDS classified as intermediate-1, intermediate-2 or high risk as per the International Prognostic Scoring System-Revised (IPSS-R) score with a confirmed diagnosis of MDS with cytogenetic abnormalities at diagnosis and bone marrow blast percentage between 10 and 30 percent (for patients with cytogenetic failure or dry tap)
- Potential participants must meet ONE of the following:
- Off all other treatments for MDS for at least 3 weeks. Filgrastim (G-CSF) and erythropoietin are allowed before and during the study as clinically indicated
Key exclusion criteria (7 listed)
- Current or anticipated use of other investigational agents
- Participants who have had chemotherapy or radiotherapy within 3 weeks prior to entering the study or those who have not recovered from clinically significant adverse events due to agents administered more than 3 weeks earlier.
- History of allergic reactions or sensitivity to pyrimethamine
- Patients with a history of folic acid deficiency, currently on folic acid replacement therapy or a previous history of megaloblastic anemia thought related to folic acid deficiency
- Current use or anticipated need for treatment with any medications or substances that are inhibitors or inducers of CYP2C9.
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 |
|---|---|---|
| PyrimethamineAlso: DaraprimPyrimethamine will be administered 50mg/100mg/150mg once daily on days 1-28 of each 28-day cycle. Administered using intra-patient dose escalation, starting at 50 mg and up to 150 mg. | Drug | Pyrimethamine Treatment (Intra-patient) |
Primary outcome
Dose-limiting toxicity (DLT)
Time frame: Day 28
Determination of DLT to be made at the completion of each cohort.
Maximum tolerated dose (MTD)
Time frame: up to 28 days
The dose where no DLT is observed among 3 consecutive participants, or no more than one DLT among 6 participants.
Recommended Phase II Dose (RPTD, RP2D)
Time frame: 12 months
Pyrimethamine will be dose-escalated until the largest dose is reached that is determined to be safe based on adverse event reporting and dose-limiting toxicity information from all participants.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2021.
- 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.
Aditi Shastri, MD principal investigator
Montefiore Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pyrimethamine in people with Myelodysplastic Syndromes, run by Montefiore Medical Center 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 14 inclusion and 7 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: withdrawn, as of the sponsor's last update on 22 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 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 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 was withdrawn before enrolling participants, so there are no results.
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?
Dose-limiting toxicity (DLT) (time frame: Day 28). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Sep 2021.