Pyrimethamine for Intermediate/High-risk Myelodysplastic Syndromes (MDS) That Has Relapsed or Refractory to Azanucleosides
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|ClinicalTrials.gov Identifier: NCT03057990|
Recruitment Status : Recruiting
First Posted : February 20, 2017
Last Update Posted : September 26, 2019
|Condition or disease||Intervention/treatment||Phase|
|Myelodysplastic Syndromes||Drug: Pyrimethamine||Phase 1|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||September 11, 2019|
|Estimated Primary Completion Date :||August 2021|
|Estimated Study Completion Date :||August 2022|
Experimental: Pyrimethamine Treatment (Intra-patient)
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.
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.
Other Name: Daraprim
- 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03057990
|Contact: Karen Fehn, RNemail@example.com|
|United States, New York|
|Montefiore Medical Center||Recruiting|
|Bronx, New York, United States, 10467|
|Principal Investigator:||Aditi Shastri, MD||Montefiore Medical Center|