Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 3 for:    9-ING-41

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.
 
ClinicalTrials.gov Identifier: NCT04218071
Recruitment Status : Not yet recruiting
First Posted : January 6, 2020
Last Update Posted : June 22, 2020
Sponsor:
Collaborator:
Developmental Therapeutics Consortium
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.

Layout table for study information
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
Estimated Study Start Date : June 2020
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2022


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
9-
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
9-
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 -

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


Contacts
Layout table for location contacts
Contact: Francis J Giles, MD 2817961852 fgiles@actuatetherapeutics.com

Locations
Layout table for location information
United States, California
University of California Los Angeles
Los Angeles, California, United States, 90095
Contact: Gary Schiller, MD       GSchiller@mednet.ucla.edu   
United States, Rhode Island
Brown University
Providence, Rhode Island, United States, 02912
Contact: John Reagan       JReagan@Lifespan.org   
Sponsors and Collaborators
Actuate Therapeutics Inc.
Developmental Therapeutics Consortium
Investigators
Layout table for investigator information
Study Chair: Francis Giles, MD DTC
Publications of Results:

Layout table for additonal information
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: June 22, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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
Ruxolitinib
Jak2 inhibitors
glycogen synthase kinase 3 beta
GSK3beta
9-ING-41
Additional relevant MeSH terms:
Layout table for MeSH terms
Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases