Clinical Trials /

Actuate 1901: 9-ING-41 in Myelofibrosis

NCT04218071

Description:

9-ING-41 has anti-cancer clinical activity while not causing myelosuppression, and has both pre-clinical anti-fibrotic activity and activity against myelofibrosis. This Phase 2 study will study its efficacy in patients with advanced myelofibrosis.

Related Conditions:
  • Myelofibrosis
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Actuate 1901: 9-ING-41 in Myelofibrosis
  • Official Title: Phase 2 Study of 9-ING-41, a Glycogen Synthase Kinase 3 Beta (GSK 3β) Inhibitor, as a Single Agent or Combined With Ruxolitinib, in Patients With Myelofibrosis

Clinical Trial IDs

  • ORG STUDY ID: 1901
  • NCT ID: NCT04218071

Conditions

  • Myelofibrosis

Interventions

DrugSynonymsArms
RuxolitinibJakafi9-ING-41 plus Ruxolitinib
9-ING-419-ING-41 Compound9-ING-41

Purpose

9-ING-41 has anti-cancer clinical activity while not causing myelosuppression, and has both pre-clinical anti-fibrotic activity and activity against myelofibrosis. This Phase 2 study will study its efficacy in patients with advanced myelofibrosis.

Detailed Description

      9-ING-41 is a first-in-class, intravenously administered, maleimide-based, small molecule,
      potent selective GSK-3β inhibitor with significant pre-clinical and clinical anticancer
      activity. In the ongoing Actuate 1801 study in a cohort of over 90 patients with advanced
      refractory malignancies, 9-ING-41 has exhibited no significant toxicity, including no
      myelosuppression, and significant anti-tumor activity. 9-ING-41 also has significant
      pre-clinical ability to reverse pathologic fibrosis in multiple models of pulmonary and
      pleural fibrosis. Reversal of fibrosis by an anti-fibrotic agent in patients with advanced
      myelofibrosis (MF) has recently been demonstrated to be of clinical benefit. 9-ING-41 has the
      potential to act both as an anti-neoplastic agent (without causing myelosuppression) and an
      anti-fibrotic agent in patients with MF. The efficacy of Ruxolitinib is limited in many
      patients by the inability to tolerate adequate doses for an adequate duration with
      myelosuppression being a frequent dose limiting toxicity. 9-ING-41 may reduce the dose of
      Ruxolitinib needed for optimal therapeutic response and/or reverse myelosuppression so than
      an adequate dose of Ruxolitinib can be tolerated. Pre-clinical data show synergy in MF
      between 9-ING-41 and Ruxolitinib. This Phase 2 study is designed to evaluate the efficacy of
      9-ING-41, as a single agent or in combination with Ruxolitinib, in patients with advanced,
      poor prognosis MF.
    

Trial Arms

NameTypeDescriptionInterventions
9-ING-41Experimental9-ING-41 is administered by intravenous infusion twice weekly at a dose of 9.3 mg/kg. Cycle duration is 28 days.
  • 9-ING-41
9-ING-41 plus RuxolitinibExperimental9-ING-41 9.3 mg/kg will be administered by intravenous infusion twice weekly for cycle durations of 28 days with Ruxolitinib at doses specified in the protocol as appropriate for patient's platelet count.
  • Ruxolitinib
  • 9-ING-41

Eligibility Criteria

        Inclusion Criteria:

        Patient -

          1. Is able to understand and voluntarily sign a written informed consent and is willing
             and able to comply with the protocol requirements including scheduled visits,
             treatment plan, laboratory tests and other study procedures

          2. Is aged ≥ 18 years

          3. Has documented diagnosis of symptomatic primary MF, PPV-MF or PET-MF as defined by the
             World Health Organization classification with a DIPSS plus score of 4 or more

          4. Is ineligible or unwilling to undergo stem cell transplantation at time of study entry

          5. Has laboratory function within specified parameters per local laboratory (may be
             repeated):

               -  Absolute neutrophil count (ANC) ≥ 100/mL; platelets ≥ 20,000/mL

               -  Transaminases (AST/ALT) and alkaline phosphatase ≤ 3 (≤ 10 X the upper limit of
                  normal (ULN) if considered to be MF-related) x ULN; bilirubin ≤ 1.5 x ULN (unless
                  patient has Gilbert's Syndrome)

               -  Serum amylase and lipase ≤ 1.5 x ULN

          6. Has adequate performance status (PS): Eastern Co-operative Oncology Group (ECOG) PS
             0-2

          7. Has received the final dose of any of the following treatments/procedures with the
             specified minimum intervals before first dose of 9-ING-41 (unless in the opinion of
             the investigator and the study medical coordinator the treatments/procedures will not
             compromise patient safety or interfere with study conduct:

               -  Chemotherapy, immunotherapy, or systemic radiation therapy - 14 days maximum, or
                  ≥ 5 half-lives (whichever is shorter)

               -  Surgery with general anesthesia - 7 days

          8. Patients who are to receive 9-ING-41 plus Ruxolitinib must have attempted ≥12 weeks of
             Ruxolitinib therapy and required dose reductions/interruptions and/or had an
             inadequate response

          9. Women of childbearing potential must have a negative baseline blood or urine pregnancy
             test within 72 hours of first study therapy. Women may be neither breastfeeding nor
             intending to become pregnant during study participation and must agree to use
             effective contraceptive methods (hormonal or barrier method of birth control, or true
             abstinence) for the duration of study participation and in the following 100 days
             after discontinuation of study treatment

         10. Male patients with partners of childbearing potential must take appropriate
             precautions to avoid fathering a child from screening until 100 days after
             discontinuation of study treatment and use appropriate barrier contraception or true
             abstinence

         11. Must not be receiving any other investigational product

        Exclusion Criteria:

        Patient -

          1. Is pregnant or lactating

          2. Is known to be hypersensitive to any of the components of 9-ING-41 or to the
             excipients used in its formulation

          3. Has >10% blasts in peripheral blood or bone marrow biopsy

          4. Has had a myocardial infarction within 12 weeks of the first dose of 9-ING-41

          5. Has any medical and/or social condition which, in the opinion of the investigator or
             study medical coordinator would preclude study participation

          6. Is considered to be a member of a vulnerable population (for example, prisoners)

          7. Herbal preparations / medications are prohibited throughout the study. These herbal
             medications include, but are not limited to St. John's wort, Kava, ephedra (ma huang),
             Gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and Ginseng.
             Patients should stop using cannabinoids or herbal preparations/medications at least 7
             days prior to first dose of study treatment -
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate
Time Frame:3-24 months
Safety Issue:
Description:The percent of patients with response will be assessed at the protocol specified timepoints according to the Revised IWG-MRT and ELN Response Criteria for MF (2013)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Actuate Therapeutics Inc.

Trial Keywords

  • primary myelofibrosis
  • post polycythemia vera myelofibrosis
  • post essential thrombocythemia myelofibrosis
  • Ruxolitinib
  • Jak2 inhibitors
  • glycogen synthase kinase 3 beta
  • GSK3beta
  • 9-ING-41

Last Updated

May 17, 2020