A Study Evaluating Tolerability and Efficacy of Navitoclax in Combination With Ruxolitinib in Subjects With Myelofibrosis

Overview

About this study

This is a Phase 2, single-arm, open-label, multicenter study evaluating efficacy, safety and tolerability of navitoclax added to ruxolitinib in participants with myelofibrosis.

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. If you need assistance understanding the eligibility criteria, please contact the study team.

Inclusion Criteria:

  • Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.
  • Subject must be ≥ 18 years of age.
  • Subjects with documented diagnosis of primary MF, post-PV MF, or post-ET MF as defined by the World Health Organization classification.
  • Subject must be ineligible or unwilling to undergo stem cell transplantation at time of study entry.
  • ECOG 0, 1, or 2.
  • Cohort 1a only:
    • Subject must have received ruxolitinib therapy for at least 12 weeks and be currently on a stable dose of ≥ 10 mg BID of ruxolitinib for ≥ 8 weeks prior to the 1st dose of navitoclax.
      • Note: Subjects with ruxolitinib dose reductions within 8 weeks prior to study enrollment may be considered on a stable dose if stable at that decreased dose of ruxolitinib for ≥ 2 weeks prior to the 1st dose of navitoclax. If the dose reduction was due to thrombocytopenia, the platelets must be confirmed to be stable by a repeat laboratory test.
  • Cohort 1b only:
    • Subject must have received prior treatment with JAK-2 inhibitor therapy for at least 12 weeks
  • Cohort 2 only:
    • Subject must have received prior treatment with JAK-2 inhibitor therapy and meet one of the following criteria (a or b):
      • Prior treatment with JAK-2 inhibitor for at least 12 weeks
      • Prior treatment with JAK-2 inhibitor for ≥ 28 days complicated by any of the following:
        • Development of red blood cell transfusion requirement (at least 2 units/month for 2 months; or
        • Grade ≥ 3 adverse events of thrombocytopenia, anemia, hematoma and/or hemorrhage while on JAK-2 inhibitor treatment
  • Cohort 3 only:
    • Subject must not have received prior treatment with a JAK-2 inhibitor.
  • Subject has splenomegaly defined as a spleen palpation measurement ≥ 5 cm below costal margin or spleen volume ≥ 450 cm^3 as assessed by MRI.
  • Subject must meet the following laboratory parameters per local laboratory reference range at Screening:
    • Adequate bone marrow reserves; in the absence of growth factors, thrombopoietic factors, or platelet transfusions for at least 14 days:
      • Platelet count ≥ 100 × 10^9/L (Cohorts 1a, 1b or 3);
      • Platelet count ≥ 75 x 10^9 (Cohort 2);
      • ANC ≥ 1 × 10^9/L.
    • Renal function: calculated creatinine clearance ≥ 30 mL/min.
    • Hepatic function and enzymes:
      • AST and ALT ≤ 3.0 × upper normal limit (ULN);
      • Bilirubin ≤ 1.5 × ULN (exception: subjects with Gilbert's Syndrome may have a Bilirubin > 1.5 × ULN).
    • Coagulation:
      • aPTT ≤ 1.5 × ULN;
      • INR ≤ 1.5 × ULN.
  • If female, subject must be either postmenopausal defined as:
    • Age > 55 years with no menses for 12 or more months without an alternative medical cause;
    • Age ≤ 55 years with no menses for 12 or more months without an alternative medical cause AND an FSH level > 40 IU/L; OR
    • Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy); OR
    • A Women of Childbearing Potential (WOCBP) practicing at least one protocol specified method of birth control, starting at Study Day 1 through at least 30 days after the last dose of study drug.
  • If the male subject is sexually active, he must agree, from Study Day 1 through at least 30 days after the last dose of study drug, to practice the protocol specified contraception.
  • Females of childbearing potential must have a negative serum pregnancy test result at Screening, and a negative urine pregnancy test at Study Day 1.
  • Females of non-childbearing potential (either postmenopausal or permanently surgically sterile as defined above) at Screening do not require pregnancy testing.

Exclusion Criteria:

  • Splenic irradiation within 12 months prior to screening, or prior splenectomy.
  • Leukemic transformation (> 10% blasts in peripheral blood or bone marrow biopsy).
  • Subject is currently on medications that interfere with coagulation (including warfarin) or platelet function with the exception of low dose aspirin (up to 100 mg) and LMWH.
  • Prior therapy with a BH3 mimetic compound.
  • Subject has a history of an active malignancy other than MF within the past 2 years prior to study entry, with the exception of:
    • Adequately treated in situ carcinoma of the cervix uteri;
    • Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin;
    • Asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy.
  • Subject has a known positive test for HIV.
    • Note: HIV testing is not required at Screening.
  • Subject has chronic active hepatitis B (HBV) or hepatitis C (HCV) requiring treatment.
  • Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
    • Ongoing systemic infection (viral, bacterial, or fungal);
    • Febrile neutropenia.
  • Subject has received any of the following within 14 days prior to the first dose of study drug:
    • Strong or moderate CYP3A inhibitors.
  • 10. Subject has consumed one or more of the following within 3 days prior to the first dose of study drug:
    • Grapefruit or grapefruit products;
    • Seville oranges (including marmalade containing Seville oranges);
    • Star fruit (carambola).
  • Female subject who is pregnant, breastfeeding or is considering becoming pregnant during the study or for approximately 30 days after the last dose of study drug.  Male subject who is considering fathering a child or donating sperm during the study or for approximately 90 days after the last dose of study drug.
  • Subject has history of a cardiovascular, endocrinologic, hepatic, immunologic metabolic, neurologic, psychiatric, pulmonary, renal disease, or any other condition that in the opinion of the investigator would adversely affect his/her participation in this study or interpretation of study results.
    • Note: For subjects who have required an intervention for any above diseases within the past 6 months a discussion between the investigator and the TA MD/SD must take place prior to any decision to enroll the patient with the agreement of the AbbVie TA MD/SD.
  • Subject is concurrently participating in another therapeutic clinical trial.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

James Foran, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

James Foran, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

James Foran, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20423882

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