Clinical Trials /

A Phase 2 Study of CPI-0610 With and Without Ruxolitinib in Patients With Myelofibrosis

NCT02158858

Description:

Phase 1 Part (Complete): Open-label, sequential dose escalation study of CPI-0610 in patients with previously treated Acute Leukemia, Myelodysplastic Syndrome, Myelodysplastic/Myeloproliferative Neoplasms, and Myelofibrosis. Phase 2 Part: Open-label study of CPI-0610 with and without Ruxolitinib in patients with Myelofibrosis. CPI-0610 is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.

Related Conditions:
  • Myelofibrosis
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase 2 Study of CPI-0610 With and Without Ruxolitinib in Patients With Myelofibrosis
  • Official Title: A Phase 1/2 Study of CPI-0610, a Small Molecule Inhibitor of BET Proteins: Phase 1 (in Patients With Hematological Malignancies) and Phase 2 (Dose Expansion of CPI-0610 With and Without Ruxolitinib in Patients With Myelofibrosis)

Clinical Trial IDs

  • ORG STUDY ID: 0610-02
  • NCT ID: NCT02158858

Conditions

  • Myelofibrosis
  • Leukemia, Myelocytic, Acute
  • Myelodysplastic/Myeloproliferative Neoplasm
  • Myelodysplastic Syndrome (MDS)

Interventions

DrugSynonymsArms
CPI-0610Arm 1: Prior JAKi (JAK inhibitor) Monotherapy Arm
RuxolitinibArm 2: Prior JAKi Combination Arm

Purpose

Phase 1 Part (Complete): Open-label, sequential dose escalation study of CPI-0610 in patients with previously treated Acute Leukemia, Myelodysplastic Syndrome, Myelodysplastic/Myeloproliferative Neoplasms, and Myelofibrosis. Phase 2 Part: Open-label study of CPI-0610 with and without Ruxolitinib in patients with Myelofibrosis. CPI-0610 is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.

Trial Arms

NameTypeDescriptionInterventions
Arm 1: Prior JAKi (JAK inhibitor) Monotherapy ArmExperimentalCohort 1A: Open to patients with MF who are Transfusion Dependent (TD) and who have previously been treated with a JAKi and are intolerant, resistant, refractory or lost response to the JAKi, or are ineligible to be treated with a JAKi.(CPI-0610 alone) Cohort 1B: Open to patients with MF who are not TD and who have previously been treated with a JAKi and are intolerant, resistant, refractory or lost response to the JAKi, or are ineligible to be treated with a JAKi. (CPI-0610 alone)
  • CPI-0610
Arm 2: Prior JAKi Combination ArmExperimentalCohort 2A: Open to patients with MF who are Transfusion Dependent (TD) and are currently taking ruxolitinib but have disease that is not being adequately controlled by ruxolitinib. (CPI-0610 + Ruxolitinib) Cohort 2B: Open to patients with MF who are not TD and are currently taking ruxolitinib but have disease that is not being adequately controlled by ruxolitinib. (CPI-0610 + Ruxolitinib)
  • CPI-0610
  • Ruxolitinib
Arm 3: JAKi Naïve Combination ArmExperimental• Open to patients with MF who are anemic (i.e., Hemoglobin (Hgb) <10g/dL) and who have not previously received a JAKi. (CPI-0610 + Ruxolitinib)
  • CPI-0610
  • Ruxolitinib

Eligibility Criteria

        Inclusion Criteria

          -  Adult (aged ≥ 18 years)

          -  Phase 2 part: Patients with confirmed diagnosis of MF who meet all of the following
             criteria:

               -  Dynamic International Prognostic Scoring System (DIPSS) risk category of
                  intermediate-1 or higher.

               -  ANC ≥ 1 x 10^9/L without the assistance of granulocyte growth factors

               -  Peripheral blood blast count <10%

          -  ECOG performance status ≤ 2.

          -  Adequate hematological, renal, hepatic, and coagulation laboratory assessments

          -  Patients must give written informed consent to participate in this study before the
             performance of any study-related procedure.

        For Arm 1 and 2 the following criteria should be considered:

          -  Palpable spleen ≥ 5 cm that is below the costal margin on physical examination OR RBC
             transfusion dependent (defined as an average of ≥2 units of RBC transfusions per month
             over the 12 weeks prior to enrollment)

          -  At least 2 symptoms measurable (score ≥ 1) using the Myelofibrosis Symptom Assessment
             Form Version 4.0 (MFSAF v4.0)

          -  Platelet count ≥ 75 x 10^9/L without the assistance of thrombopoietic factors or
             transfusions for at least 14 days

          -  Monotherapy Arm (Arm 1): Previously treated with a JAK inhibitor and be intolerant,
             resistant, refractory or lost response to the JAK inhibitor

          -  Combination Arm (Arm 2): Must have received single agent ruxolitinib and be on a
             stable dose for a minimum 8 weeks

        For Arm 3 (JAK inhibitors naïve) the following criteria should be considered:

          -  Platelet count ≥ 100 x 10^9/L without the assistance of thrombopoietic factors or
             transfusions

          -  Palpable spleen ≥ 5 cm that is below the costal margin on physical examination

          -  At least 2 symptoms measurable (score ≥ 3) or a total score of ≥ 10 using the MFSAF
             v4.0

          -  No prior treatment with JAKi allowed

        Exclusion Criteria

          -  Current known active or chronic infection with human immunodeficiency virus (HIV),
             Hepatitis B or Hepatitis C.

          -  Impaired cardiac function or clinically significant cardiac diseases

          -  Patients with Child-Pugh Class B or C

          -  Impairment of gastrointestinal (GI) function or GI disease that could significantly
             alter the absorption of CPI-0610 and/or ruxolitinib, including any unresolved nausea,
             vomiting, or diarrhea that is CTCAE grade >1

          -  Prior treatment with a BET inhibitor.

          -  Pregnant or lactating women

          -  Any other concurrent severe and/or uncontrolled concomitant medical condition that
             could compromise participation in the study

          -  Patients unwilling or unable to comply with this study protocol.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 2 Part: Evaluate spleen response
Time Frame:By imaging after 24 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Phase 2 Part: Evaluate the duration of spleen response by imaging
Time Frame:By palpation and imaging after 24 weeks
Safety Issue:
Description:
Measure:Phase 2 Part: Evaluate response category rate
Time Frame:Rate of response by IWG-MRT after 24 weeks
Safety Issue:
Description:
Measure:Phase 2 Part: Evaluate the change in patient reported outcomes
Time Frame:Changes from baseline in the total symptom score (MFSAF v4.0) and PGIC after 24 weeks
Safety Issue:
Description:
Measure:Phase 2 Part: Evaluate the rate of RBC transfusion and the RBC transfusion dependence rate
Time Frame:Average number of RBC units per subject-month
Safety Issue:
Description:
Measure:Phase 2 Part: Pharmacokinetic parameters of CPI-0610 and ruxolitinib: AUC and Cmax
Time Frame:Assessed during cycle 1 (first 21 days on study)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Constellation Pharmaceuticals

Trial Keywords

  • Phase 1
  • Phase 2
  • Oncology
  • BET Inhibitor
  • Ruxolitinib

Last Updated

October 28, 2019