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

Overview

About this study

The purpose of trhis study is to evaluate CPI-0610 in patients who have both received JAK inhibitors, such as ruxolitinib (Arms 1 and 2), and in patients who have never been treated with a JAK inhibitor (Arm 3).  Patients who participate in Arm 1 will be treated with CPI-0610 alone (monotherapy arm), patients who participate in Arm 2 will be treated with CPI-0610 in combination with ruxolitinib (combination arm), and patients who have never been treated with a JAK inhibitor who participate in Arm 3, will also be treated with CPI-0610 and ruxolitinib, a JAK inhibitor (JAKi naïve arm).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria - Prior JAKi Arm 1 and Add-on to JAKi Arm 2:

Patients with confirmed diagnosis of MF who meet all of the following criteria:

  • Dynamic International Prognostic Scoring System (DIPSS) risk category of intermediate-2 or higher.
  • Platelet count ≥ 75 x 10^9/L without the assistance of thrombopoietic factors or transfusions.
  • ANC ≥ 1 x 10^9/L without the assistance of granulocyte growth factors.
  • Spleen volume of ≥ 450 cm3 by CT or MRI for Cohorts 1B and 2B OR RBC TD (defined as an average of ≥ 2 units of RBC transfusions per month over the 12 weeks prior to enrollment) for Cohorts 1A and 2A.
  • Peripheral blood blast count < 10%.
  • At least 2 symptoms measurable (score ≥ 1) using the MFSAF v4.0.
  • Monotherapy Arm (Arm 1) patients only: Previously treated with a JAKi and be intolerant, resistant, refractory or lost response to the JAKi; have not received the JAKi within 2 weeks prior to start of study drug, or are ineligible to be treated with a JAKi
  • Combination Arm (Arm 2) patients only: Must have received ruxolitinib for at least 6 months and be on a stable ruxolitinib dose for a minimum 8 weeks (prior to start of study drug).
  • ECOG performance status ≤ 2.
  • Serum direct bilirubin ≤ 1.5 x upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN. The AST and /or ALT may be elevated up to 5 x ULN if the elevation can be reasonably ascribed to liver involvement.
  • Calculated or measured creatinine clearance (CrCl) ≥ 45 ml/min.
  • No prior treatment with any bromodomain and extra-terminal domain (BET) inhibitor.

Inclusion Criteria - JAKi Naïve Arm 3:

  • Patients with confirmed diagnosis of MF who meet all of the following criteria:
    • DIPSS risk category of intermediate-2 or higher;
    • Platelet count ≥ 100 x 10^9/L without the assistance of thrombopoietic factors or transfusions;
    • ANC ≥ 1 x 10^9/L without the assistance of granulocyte growth factors;
    • Spleen volume of ≥ 450 cm^3 by CT/MR;
    • Peripheral blood blast count < 10%;
    • At least 2 symptoms measurable (score ≥ 3) or a total score of ≥ 10 using the MFSAF v4.0;
    • No prior treatment with JAKi allowed.
  • ECOG performance status ≤ 2.
  • Life expectancy of > 24 weeks.
  • Serum direct bilirubin < 2.0 x ULN; AST and ALT ≤ 2.5 x ULN. The AST and /or ALT may be elevated up to 5 x ULN if the elevation can be reasonably ascribed to liver involvement.
  • Calculated or measured CrCl ≥ 45 ml/min.
  • No prior treatment with any BET inhibitor.

Phase 2 Arm 1 (MF Expansion – Prior JAKi) and Arm 2 (Add-on to JAKi) Exclusion Criteria:

  • Patients in Cohorts 1B and 2B only: Patients who have had prior splenectomy.
  • Patients in Cohorts 1B and 2B only: Patients who have had splenic irradiation within 3 months of starting study drug.
  • Current known active or chronic infection with human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C. Screening of patients with serologic testing for these viruses is not required. However, patients who have a past history of viral hepatitis or in whom there is a current suspicion of viral hepatitis should have serologic testing for Hepatitis B and Hepatitis C performed to determine whether there is any current evidence for ongoing infection with these viruses. Patients considered to be at risk for HIV infection should have HIV testing performed. Testing for COVID-19 is not mandatory during the screening for this study. However, based on the local epidemiologic situation and each patient’s individual COVID-19 exposure risk and/or vaccination status, investigators should consider testing and in the case of COVID-19 positivity consider delaying the start of the study treatment until the infection is resolved.
  • Patients with active clinically significant infection will not be eligible for enrollment until recovery for at least 2 weeks prior to the first dose of study drug.
  • Patients with anemia deemed clinically significant by the investigator from iron deficiency, B12 and folate deficiencies, or hemolytic anemia.
  • Patient with a major bleeding event causing a decrease in Hgb of ≥ 2g/dL or leading to transfusion of ≥ 2 units of packed red cells in the last 6 months prior to enrollment.
  • Patients with liver cirrhosis Child-Pugh Class B or C.
  • Impairment of GI function or GI disease that could significantly alter the absorption of CPI-0610 and/or ruxolitinib, including any unresolved nausea, vomiting, or diarrhea > CTCAE Grade 1.
  • Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
    • Acute myocardial infarction or unstable angina pectoris ≤ 6 months prior to starting study drug;
    • QTcF > 500 msec on the screening ECG;
    • Uncontrolled clinically significant cardiac arrhythmia (patients with rate-controlled atrial fibrillation are not excluded).
    • Note that patients with a history of coronary artery disease and revascularization are not excluded.
  • Ongoing uncontrolled hypertension despite maximal antihypertensive treatment.
  • Any other concurrent severe and/or uncontrolled concomitant medical condition that in the opinion of the investigator could compromise participation in the study or analysis of study data. This includes but is not limited to clinically significant pulmonary disease or neurological disorders, or active or uncontrolled infections.
  • Systemic anticancer treatment (other than ruxolitinib for the Combination Arm [Arm 2]; other than HU and ANA less than 2 weeks (or 5 half-lives, whichever is longer) before the first dose of CPI-0610.
    • NOTE: HU and ANA are permitted to be used up to 24 hours prior to start of study drug.
  • Any investigational agent (whether as cancer treatment or not) less than 2 weeks (or 5 halflives, whichever is longer) before the first dose of CPI-0610.
  • Prior treatment with a BET inhibitor.
  • Hematopoietic growth factor (granulocyte growth factor, erythropoiesis stimulating agent, thrombopoietin mimetic) or androgenic steroids less than 4 weeks before the first dose of study drug.
  • Patients in the Combination Arm (Arm 2) who are receiving treatment with fluconazole.
    • NOTE: Patients in the Combination Arm who, at the time of screening, are already on a strong CYP3A4 inducer or inhibitor may be eligible, provided they meet all the other eligibility criteria. Initiation of treatment of a strong CYP3A4 inhibitor or inducer during study treatment in Combination Arm patients is prohibited.
  • Systemic corticosteroids at daily doses ≥ 10 mg of oral prednisone or equivalent within 4 weeks before the first dose of study drug.
    • NOTE: Patients who received daily doses of > 5 and < 10 mg oral prednisone or equivalent for ≤ 10 days within 2 weeks before the first dose of study drug may be eligible after consultation with the Sponsor Medical Monitor or designee. Topical, intra-articular injection, nasal and inhaled corticosteroids or daily doses of ≤ 5 mg oral prednisone or equivalent are allowed.
  • Have a history of a concurrent or second malignancy except for adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostatespecific antigen for ≥ 1 year prior to randomization, adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 3 years.
  • Females who are breastfeeding or pregnant as documented by a serum beta-human chorionic gonadotropin (β-hCG) pregnancy test consistent with pregnancy, obtained within 72 hours prior to the first dose of CPI-0610. Females of non-childbearing potential (postmenopausal for more than 1 year; underwent a hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) do not require a serum pregnancy test.
  • Patients unwilling or unable to comply with this study protocol.

Eligibility last updated 8/12/21.  Questions regarding updates should be directed to the study team contact.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Jeanne Palmer, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Candido Rivera Linares, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available
.
CLS-20493137

Mayo Clinic Footer