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Actuate 1901: 9-ING-41 in Myelofibrosis

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ClinicalTrials.gov Identifier: NCT04218071
Recruitment Status : Recruiting
First Posted : January 6, 2020
Last Update Posted : May 2, 2022
Information provided by (Responsible Party):
Actuate Therapeutics Inc.

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.

Condition or disease Intervention/treatment Phase
Myelofibrosis Drug: Ruxolitinib Drug: 9-ING-41 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 58 participants
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
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
Actual Study Start Date : August 20, 2020
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : March 2023

Arm Intervention/treatment
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.
Drug: 9-ING-41
Other Name: 9-ING-41 Compound

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
Ruxolitinib at protocol-specified doses for given platelet count
Other Name: Jakafi

Drug: 9-ING-41
Other Name: 9-ING-41 Compound

Primary Outcome Measures :
  1. 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)

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

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 -

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): NCT04218071

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Contact: Steven D Reich, MD (858) 204-6321 sreich@actuatetherapeutics.com
Contact: Andrew P Mazar, PhD (858) 922-6618 amazar@actuatetherapeutics.com

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United States, California
University of Southern California Recruiting
Los Angeles, California, United States, 90033
Contact: Casey O'Connell, MD       coconnel@usc.edu   
University of California Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Gary Schiller, MD       GSchiller@mednet.ucla.edu   
United States, Georgia
Georgia Cancer Center Recruiting
Augusta, Georgia, United States, 30912
Contact: Jorge Cortes, MD       Jorge.cortes@augusta.edu   
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Naseema Gangat, MD       Gangat.Naseema@mayo.edu   
United States, Missouri
Siteman Cancer Center Recruiting
Saint Louis, Missouri, United States, 63100
Contact: Stephen Oh, MD       stoh@wustl.edu   
United States, New York
Weill Cornell Medicine | NewYork-Presbyterian Meyer Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Ellen Ritchie, MD    646-962-9305    ritchie@med.cornell.edu   
United States, North Carolina
Duke Cancer Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Lindsay Rein, MD       lindsay.magura@duke.edu   
United States, Rhode Island
Brown University Recruiting
Providence, Rhode Island, United States, 02912
Contact: John Reagan       JReagan@Lifespan.org   
United States, Washington
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109
Contact: Vivian Oehler, MD       voehler@uw.edu   
Sponsors and Collaborators
Actuate Therapeutics Inc.
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Study Director: Steven D Reich, MD Actuate Therapeutics Inc.
Publications of Results:

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Responsible Party: Actuate Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT04218071    
Other Study ID Numbers: 1901
First Posted: January 6, 2020    Key Record Dates
Last Update Posted: May 2, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Actuate Therapeutics Inc.:
primary myelofibrosis
post polycythemia vera myelofibrosis
post essential thrombocythemia myelofibrosis
Jak2 inhibitors
glycogen synthase kinase 3 beta
Additional relevant MeSH terms:
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Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases