A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Idasanutlin Monotherapy in Participants With Hydroxyurea-Resistant/Intolerant Polycythemia Vera

Official Title

A Phase II, Single-Arm, Open-Label Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Idasanutlin Monotherapy in Patients With Hydroxyurea-Resistant/Intolerant Polycythemia Vera

Summary:

This is an open-label, single-arm study of idasanutlin monotherapy in participants with hydroxyurea (HU)-resistant/intolerant Polycythemia vera (PV). The study will include two phases: initial phase and expansion phase. The initial phase will assess the safety and efficacy of idasanutlin monotherapy in ruxolitinib naïve and ruxolitinib-resistant or intolerant patients, respectively. If the initial phase shows promising results for ruxolitinib-resistant or intolerant patients, an expansion phase will be opened to further characterize the efficacy of idasanutlin.

Trial Description

Primary Outcome:

  • Percentage of Ruxolitinib-Naïve Participants With Splenomegaly at Baseline who Achieved Composite Response at Week 32
  • Percentage of Ruxolitinib-Naïve Participants Without Splenomegaly at Baseline who Achieved Hematocrit (Hct) Control Without Phlebotomy at Week 32
  • Percentage of All Ruxolitinib-Naïve Participants (Irrespective of Spleen Size) who Achieved Hct Control Without Phlebotomy at Week 32
  • Percentage of All Ruxolitinib-Resistant or Intolerant Participants who Achieved Hct Control Without Phlebotomy at Week 32
Secondary Outcome:
  • Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants who Achieved Complete Hematologic Response at Week 32
  • Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants who Achieved Complete Hematologic Remission at Cycle 11 Day 28
  • Duration of Complete Hematologic Remission, with a Durable Responder Defined as a Participant in Remission at Week 32 and Cycle 11 Day 28
  • Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly at Baseline by Response per Modified European Leukemia Net (ELN) Criteria
  • Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly at Baseline by Response per Modified ELN Criteria
  • Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants (Irrespective of Spleen Size) by Response per Modified ELN Criteria
  • Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks from Week 32
  • Duration of Response, in Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly at Baseline with Durable Response Lasting at Least 12 Weeks From Week 32
  • Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks from Week 32
  • Duration of Response, in Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly at Baseline with Durable Response Lasting at Least 12 Weeks From Week 32
  • Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants (Irrespective of Spleen Size) With Durable Response Lasting at Least 12 Weeks from Week 32
  • Duration of Response, in All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants (Irrespective of Spleen Size) with Durable Response Lasting at Least 12 Weeks From Week 32
  • Total Number of Participants With Adverse Events by Severity, Graded According to NCI CTCAE v4.0
  • Percentage of Participants With Clinical Laboratory Abnormalities: Hematology Parameters
  • Percentage of Participants With Clinical Laboratory Abnormalities: Clinical Chemistry Parameters
  • Percentage of Participants With Clinical Laboratory Abnormalities: Urinalysis Parameters
  • Change from Baseline in Electrocardiogram Parameters: PQ(PR), QRS, QT, QTcB, QTcF, and RR Durations
  • Change from Baseline in Heart Rate, as Measured by Electrocardiogram
  • Change from Baseline in Oral Temperature
  • Change from Baseline in Pulse Rate
  • Change from Baseline in Respiratory Rate
  • Change from Baseline in Systolic Blood Pressure
  • Change from Baseline in Diastolic Blood Pressure
  • Eastern Cooperative Oncology Group (ECOG) Performance Status Over Time
  • Percentage of Participants With Concomitant Medications
  • Maximum Serum Concentration Observed (Cmax) of Idasanutlin
  • Trough Concentration (Ctrough) of Idasanutlin
  • Time of Maximum Concentration Observed (tmax) of Idasanutlin
  • Clearance (CL) of Idasanutlin
  • Apparent Clearance (CL/F) of Idasanutlin
  • Volume or Apparent Volume of Distribution (Vdss/F) of Idasanutlin
  • Area Under the Concentration-Time Curve (AUC) of Idasanutlin
  • Half-life (t1/2) of Idasanutlin
  • Baseline and Mean Change from Baseline Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) Over Time
  • Baseline and Mean Change from Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores Over Time
  • Frequency Count of Participant Responses to the Patient Global Impression of Change (PGIC) Question Over Time

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

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