Intra-patient Dose Escalation Study to Investigate Safety and Feasibility of Vactosertib in Treating Anemic MPN Patients

This study assesses the potential of using a TGFβ receptor inhibitor for the treatment of anemic patients with myeloproliferative neoplasms. TGFβ signaling is known to be abnormally high in patients with myeloproliferative neoplasms and it is thought that abnormal TGFβ signals cause many of the problems with blood cell formation in these diseases. The study design allows all patients to receive the study drug, vactosertib. The dose of vactosertib is individualized within a pre-set range based upon its effectiveness and tolerability. A total of up to 37 patients will be treated.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

Patients who meet the WHO 2016 criteria for a Ph-neg MPN (including PV, ET, MF, MDS/MPN, MPN-U).

* 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:

* Any other serious medical condition which in the Investigator's opinion would preclude safe participation in the study.
* 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.

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