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

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ClinicalTrials.gov Identifier: NCT02158858
Recruitment Status : Recruiting
First Posted : June 9, 2014
Last Update Posted : October 12, 2018
Sponsor:
Collaborator:
The Leukemia and Lymphoma Society
Information provided by (Responsible Party):
Constellation Pharmaceuticals

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Myelofibrosis Leukemia, Myelocytic, Acute Myelodysplastic/Myeloproliferative Neoplasm Myelodysplastic Syndrome (MDS) Drug: CPI-0610 Drug: Ruxolitinib Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 169 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Study Start Date : June 2014
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : March 2020


Arm Intervention/treatment
Experimental: Arm 1: Prior JAKi (JAK inhibitor) Monotherapy Arm
  • Cohort 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)
Drug: CPI-0610
Experimental: Arm 2: Prior JAKi Combination Arm
  • Cohort 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)
Drug: CPI-0610
Drug: Ruxolitinib
Experimental: Arm 3: JAKi Naïve Combination Arm
• 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)
Drug: CPI-0610
Drug: Ruxolitinib



Primary Outcome Measures :
  1. Phase 2 Part: Evaluate spleen response [ Time Frame: By imaging after 24 weeks ]
  2. Phase 2 Part: Evaluate the RBC (Red Blood Cell) transfusion independence rate [ Time Frame: Absence of RBC transfusion and no hemoglobin level below 8 g/dL in the prior 12 weeks ]

Secondary Outcome Measures :
  1. Phase 2 Part: Evaluate the duration of spleen response by imaging [ Time Frame: By palpation and imaging after 24 weeks ]
  2. Phase 2 Part: Evaluate response category rate [ Time Frame: Rate of response by IWG-MRT after 24 weeks ]
  3. 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 ]
  4. 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 ]
  5. Phase 2 Part: Pharmacokinetic parameters of CPI-0610 and ruxolitinib: AUC and Cmax [ Time Frame: Assessed during cycle 1 (first 21 days on study) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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; see Appendix 3) 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
  • Anemic, defined as a hemoglobin < 10g/dL
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02158858


Contacts
Contact: Debbie Johnson 617-714-0555 debbie.johnson@constellationpharma.com

Locations
United States, California
UCLA Medical Center Recruiting
Los Angeles, California, United States, 90095
Contact: Farzam Hariri       FHariri@mednet.ucla.edu   
Principal Investigator: Gary Schiller, MD         
United States, Indiana
Horizon Oncology Center Recruiting
Lafayette, Indiana, United States, 47905
Contact: Wael Harb, MD    765-446-5111    info@horizonbioadvance.com   
Principal Investigator: Wael Harb, MD         
United States, Massachusetts
Massachusetts General Hospital Active, not recruiting
Boston, Massachusetts, United States, 02114
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Frank Fabris    212-241-8999    frank.fabris@mssm.edu   
Principal Investigator: Marina Kremyanskya, MD PhD         
Columbia University Medical Centre Recruiting
New York, New York, United States, 10032
Contact: Mackenzie Snead       mbs2173@cumc.columbia.edu   
Principal Investigator: Mark Heaney         
Memorial Sloan-Kettering Cancer Center Active, not recruiting
New York, New York, United States, 10065
United States, Ohio
Gabrail Cancer Center Recruiting
Canton, Ohio, United States, 44718
Contact: Carrie Smith, RN       CSmith@GabrailCancerCenter.com   
Principal Investigator: Nashat Gabrail, MD         
United States, Pennsylvania
University of Pennsylvania - Perelman Center for Advanced Medicine Active, not recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Kurt Schroeder, RN    713-563-2622    kdschroe@mdanderson.org   
Principal Investigator: Prithviraj Bose, MD         
Canada, Alberta
University of Alberta Hospital Recruiting
Edmonton, Alberta, Canada, T6G 2G3
Contact: Lori Rackel    780-407-1811    lori.rackel@albertahealthservices.ca   
Principal Investigator: Elena Liew, MD         
Canada, British Columbia
St. Paul's Hospital Recruiting
Vancouver, British Columbia, Canada, V6Z 2A5
Contact: Rachel Despotovic    604-875-5296    rachel.despotovic@vch.ca   
Principal Investigator: Lynda Foltz, MD         
Canada, Ontario
Juravinski Cancer Centre Recruiting
Hamilton, Ontario, Canada, L8V 5C2
Contact: Elisa Shore       elisa.shore@jcc.hhsc.ca   
Principal Investigator: Brian Leber         
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Sabina Naqvi    416-581-8619    sabina.naqvi@uhn.ca   
Principal Investigator: Vikas Gupta, MD         
Sponsors and Collaborators
Constellation Pharmaceuticals
The Leukemia and Lymphoma Society
Investigators
Study Director: Debbie Johnson Constellation Pharmaceuticals

Responsible Party: Constellation Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02158858     History of Changes
Other Study ID Numbers: 0610-02
First Posted: June 9, 2014    Key Record Dates
Last Update Posted: October 12, 2018
Last Verified: October 2018

Keywords provided by Constellation Pharmaceuticals:
Phase 1
Phase 2
Oncology
BET Inhibitor
Ruxolitinib

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Primary Myelofibrosis
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Leukemia
Neoplasms by Histologic Type