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Actuate 1901: 9-ING-41 in Myelofibrosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04218071
Recruitment Status : Recruiting
First Posted : January 6, 2020
Last Update Posted : May 2, 2022
Information provided by (Responsible Party):
Actuate Therapeutics Inc.

Tracking Information
First Submitted Date  ICMJE January 2, 2020
First Posted Date  ICMJE January 6, 2020
Last Update Posted Date May 2, 2022
Actual Study Start Date  ICMJE August 20, 2020
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 3, 2020)
Response rate [ Time Frame: 3-24 months ]
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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Actuate 1901: 9-ING-41 in Myelofibrosis
Official Title  ICMJE 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
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Patients will receive either single agent 9-ING-41 or 9-ING-41 plus Ruxolitinib
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Myelofibrosis
Intervention  ICMJE
  • Drug: Ruxolitinib
    Ruxolitinib at protocol-specified doses for given platelet count
    Other Name: Jakafi
  • Drug: 9-ING-41
    Other Name: 9-ING-41 Compound
Study Arms  ICMJE
  • Experimental: 9-ING-41
    9-ING-41 is administered by intravenous infusion twice weekly at a dose of 9.3 mg/kg. Cycle duration is 28 days.
    Intervention: Drug: 9-ING-41
  • Experimental: 9-ING-41 plus Ruxolitinib
    9-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.
    • Drug: Ruxolitinib
    • Drug: 9-ING-41
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 3, 2020)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2023
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  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 -
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Steven D Reich, MD (858) 204-6321
Contact: Andrew P Mazar, PhD (858) 922-6618
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT04218071
Other Study ID Numbers  ICMJE 1901
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Actuate Therapeutics Inc.
Study Sponsor  ICMJE Actuate Therapeutics Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Steven D Reich, MD Actuate Therapeutics Inc.
PRS Account Actuate Therapeutics Inc.
Verification Date April 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP