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

  • STATUS
    Recruiting
  • End date
    Sep 28, 2023
  • participants needed
    37
  • sponsor
    Weill Medical College of Cornell University
Updated on 28 January 2021
anemia
hydroxyurea
ruxolitinib
myelodysplastic/myeloproliferative neoplasm

Summary

This study assesses the potential of using a TGF receptor inhibitor for the treatment of anemic patients with myeloproliferetive neoplasms. TGF signaling is known to be abnormally high in patients with myeloproliferative neoplasms and it is thought that abnormal TGF 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.

Description

This is a two-tiered single arm Phase 2 trial of vactosertib (TEW-7197) for the treatment of anemia in Ph-neg MPNs. Both tiers use a rule-based, accelerated dose escalation scheme to efficiently assess the potential of vactosertib to safely and effectively treat anemic patients with Ph-neg MPNs. The first tier of this trial (Tier 1) is an intra-patient dose finding study in 12 patients that uses a low starting dose of vactosertib for all patients. For each patent, the treatment dose is escalated according to prospectively-defined rules, and a toxicity and treatment effect algorithm during the period of 16 weeks (4 treatment cycles). If pre-established efficacy and safety endpoints are met (section 5.4, section 9.1, section 11.1), then Tier 1 of the study will be followed by a Tier 2 expansion study with an additional 25 patients for a period of 24 weeks (6 treatment cycles).

Vactosertib will be administered as monotherapy and therefore patients must be off cytoreductive therapies such as interferon, ruxolitinib, hydroxyurea, DNA hypomethylating agents or other cytotoxic chemotherapy prior to enrollment for a period of at least 14 days or 5 half-lives, whichever is longer. 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).

Details
Condition MYELOPROLIFERATIVE DISORDER, Myeloproliferative Neoplasms, myeloproliferative neoplasm, myeloproliferative disorders
Treatment Vactosertib
Clinical Study IdentifierNCT04103645
SponsorWeill Medical College of Cornell University
Last Modified on28 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: myeloproliferative neoplasm or MYELOPROLIFERATIVE DISORDER or myeloproliferative disorders or Myeloproliferative Neoplasms?
Do you have any of these conditions: myeloproliferative neoplasm or myeloproliferative disorders or Myeloproliferative Neoplasms or MYELOPROLIFERATIVE DISORDER?
Do you have any of these conditions: myeloproliferative disorders or MYELOPROLIFERATIVE DISORDER or Myeloproliferative Neoplasms or myeloproliferative neoplasm?
Patients who meet the WHO 2016 criteria for a Ph-neg MPN (including PV, ET
MF, MDS/MPN, MPN-U)
Patients with DIPSS Int-2 or High-risk MF (primary of post-PV/ET) must have had inadequate response to ruxolitinib
Patients with PV or ET should be refractory or unresponsive to hydroxyurea, anagrelide or other available therapy
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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