Intra-patient Dose Escalation Study to Investigate Safety and Feasibility of Vactosertib in Treating Anemic MPN Patients
NCT ID: NCT04103645
Last Updated: 2025-07-02
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE2
2 participants
INTERVENTIONAL
2019-11-22
2024-07-10
Brief Summary
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Detailed Description
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Vactosertib will be administered concurrently with the patient's current treatment (if any). Prior to enrollment, patients must be on a stable dose of their current therapy for 3 months prior to entering the study. Supportive care measures including packed red blood cell (PRBC) transfusions for HGB \<7g/dL, or symptomatic anemia, will be permitted. Administration of erythropoiesis stimulating agents (ESAs), however, will not be permitted on the trial (patients recruited would have serum EPO \>125 U/L above which the benefit of ESAs is not supported).
Conditions
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Tier 1: Vactosertib 50 mg BID
Vactosertib intra-patient dose finding cohort.
Vactosertib
50 mg BID This drug is a TGF-Beta receptor type 1 inhibitor, by inhibiting phosphorylation of the ALK5 substrates SMAD2 and SMAD3. This inhibition could promote regeneration of normal human stem cells and proliferation of erythroid progenitors to treat the underlying hypoproliferative anemia in advanced MPNs.
Tier 1: Vactosertib 100 mg BID
Vactosertib
100 mg BID This drug is a TGF-Beta receptor type 1 inhibitor, by inhibiting phosphorylation of the ALK5 substrates SMAD2 and SMAD3. This inhibition could promote regeneration of normal human stem cells and proliferation of erythroid progenitors to treat the underlying hypoproliferative anemia in advanced MPNs.
Tier 1: Vactosertib 150 mg BID
Vactosertib
150 mg BID This drug is a TGF-Beta receptor type 1 inhibitor, by inhibiting phosphorylation of the ALK5 substrates SMAD2 and SMAD3. This inhibition could promote regeneration of normal human stem cells and proliferation of erythroid progenitors to treat the underlying hypoproliferative anemia in advanced MPNs.
Tier 1: Vactosertib 200mg BID
Vactosertib
200 mg BID This drug is a TGF-Beta receptor type 1 inhibitor, by inhibiting phosphorylation of the ALK5 substrates SMAD2 and SMAD3. This inhibition could promote regeneration of normal human stem cells and proliferation of erythroid progenitors to treat the underlying hypoproliferative anemia in advanced MPNs.
Tier 2: Vactosertib
Vactosertib
The lowest dose level of vactosertib for which no DLT was observed in Tier 1 AND The lowest dose level for which at least one of the 12 subjects enrolled on Tier 1 met Criteria for Clinical Benefit. Or, if a single dose level does not fulfil both Criterion 1 and Criterion 2, the starting dose level for Tier 2 will lowest dose from Tier 1 for which no DLT was identified.
Interventions
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Vactosertib
50 mg BID This drug is a TGF-Beta receptor type 1 inhibitor, by inhibiting phosphorylation of the ALK5 substrates SMAD2 and SMAD3. This inhibition could promote regeneration of normal human stem cells and proliferation of erythroid progenitors to treat the underlying hypoproliferative anemia in advanced MPNs.
Vactosertib
100 mg BID This drug is a TGF-Beta receptor type 1 inhibitor, by inhibiting phosphorylation of the ALK5 substrates SMAD2 and SMAD3. This inhibition could promote regeneration of normal human stem cells and proliferation of erythroid progenitors to treat the underlying hypoproliferative anemia in advanced MPNs.
Vactosertib
150 mg BID This drug is a TGF-Beta receptor type 1 inhibitor, by inhibiting phosphorylation of the ALK5 substrates SMAD2 and SMAD3. This inhibition could promote regeneration of normal human stem cells and proliferation of erythroid progenitors to treat the underlying hypoproliferative anemia in advanced MPNs.
Vactosertib
200 mg BID This drug is a TGF-Beta receptor type 1 inhibitor, by inhibiting phosphorylation of the ALK5 substrates SMAD2 and SMAD3. This inhibition could promote regeneration of normal human stem cells and proliferation of erythroid progenitors to treat the underlying hypoproliferative anemia in advanced MPNs.
Vactosertib
The lowest dose level of vactosertib for which no DLT was observed in Tier 1 AND The lowest dose level for which at least one of the 12 subjects enrolled on Tier 1 met Criteria for Clinical Benefit. Or, if a single dose level does not fulfil both Criterion 1 and Criterion 2, the starting dose level for Tier 2 will lowest dose from Tier 1 for which no DLT was identified.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Patients with MF must have DIPSS+ Intermediate or High-risk MF (primary of post-PV/ET).
* For patients receiving cytoreductive therapy, they should be on a stable dose of current cytoreductive therapy for at least 3 months prior to C1D1.
* Anemia as defined by HGB \< 10 g/dL, or transfusion of ≥ 2 packed red blood cell (PRBC) unit within the past 4 weeks with HGB ≤8.5g/dL.
* Ineligible, unsuitable or refractoriness to ESA therapy defined as any of the following:
* Serum erythropoietin (EPO) \>125 U/L.
* Proven ESA unsuitability is defined by history of any of the following:
* Loss of erythroid hematologic improvement while receiving stable or increased ESA dose; or
* ESA-attributed toxicity that, in the treating physician's opinion, makes ESA therapy unsuitable for subject.
* ESA refractoriness defined by lack of erythroid hematologic improvement to ESA:27
* Less than 1.5 g/dL increase in hemoglobin after at least 6 weeks of ESA therapy; or
* Ongoing transfusion dependence that has not been reduced by \> 4U over an 8-week period compared to ESA pre-treatment 8 weeks.
* Acceptable Cardiovascular status
Exclusion Criteria
* Patients with history of TIA or stroke within the past 12 months are excluded.
* Female subjects who are breastfeeding, or intend to breastfeed, during the study or in the 30 days following the last dose of study drug are excluded.
18 Years
ALL
No
Sponsors
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Weill Medical College of Cornell University
OTHER
Responsible Party
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Principal Investigators
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Joseph M Scandura, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Weill Medical College of Cornell University
Locations
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Weill Medical College of Cornell University
New York, New York, United States
Countries
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References
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Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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19-06020285
Identifier Type: -
Identifier Source: org_study_id
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