Ignite Creation Date:
2025-12-25 @ 12:14 AM
Ignite Modification Date:
2025-12-25 @ 10:16 PM
Study NCT ID:
NCT04730258
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-05-18
First Post:
2021-01-25
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
A Study of CFI-400945 With or Without Azacitidine in Patients With AML, MDS or CMML
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015470', 'term': 'Leukemia, Myeloid, Acute'}, {'id': 'D009190', 'term': 'Myelodysplastic Syndromes'}, {'id': 'D015477', 'term': 'Leukemia, Myelomonocytic, Chronic'}, {'id': 'D019337', 'term': 'Hematologic Neoplasms'}], 'ancestors': [{'id': 'D007951', 'term': 'Leukemia, Myeloid'}, {'id': 'D007938', 'term': 'Leukemia'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D001855', 'term': 'Bone Marrow Diseases'}, {'id': 'D054437', 'term': 'Myelodysplastic-Myeloproliferative Diseases'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000592365', 'term': "2-(3-(4-((2,6-dimethylmorpholino)methyl)styryl)-1H-indazol-6-yl)-5'-methoxyspiro(cyclopropane-1,3'-indolin)-2'-one"}, {'id': 'D001374', 'term': 'Azacitidine'}], 'ancestors': [{'id': 'D001372', 'term': 'Aza Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D003562', 'term': 'Cytidine'}, {'id': 'D011741', 'term': 'Pyrimidine Nucleosides'}, {'id': 'D011743', 'term': 'Pyrimidines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D009705', 'term': 'Nucleosides'}, {'id': 'D009706', 'term': 'Nucleic Acids, Nucleotides, and Nucleosides'}, {'id': 'D012263', 'term': 'Ribonucleosides'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'Dose escalation and expansion for monotherapy and combination arms with azacitidine'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 72}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2021-04-16', 'type': 'ACTUAL'}, 'statusVerifiedDate': '2025-05', 'completionDateStruct': {'date': '2026-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-05-16', 'studyFirstSubmitDate': '2021-01-25', 'studyFirstSubmitQcDate': '2021-01-25', 'lastUpdatePostDateStruct': {'date': '2025-05-18', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-01-29', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Incidence of treatment emergent AEs', 'timeFrame': '36 months', 'description': 'The number of subjects who experience an adverse event that was possibly related to study drug'}, {'measure': 'Treatment emergent changes in vital signs', 'timeFrame': '36 months', 'description': 'The number of subjects who experience changes in blood pressure, heart rate, respiratory rate, body temperature that was possibly related to study drug.'}, {'measure': 'Treatment emergent changes in clinical laboratory tests', 'timeFrame': '36 months', 'description': 'The number of subjects who experience a change in laboratory parameters that was possibly related to study drug.'}, {'measure': 'Treatment emergent changes in physical examinations, ECOG performance status, electrocardiograms (ECGs), echocardiograms and cardiac troponins', 'timeFrame': '36 months', 'description': 'The number of subjects who experience changes in physical examinations, performance status, ECG, troponins that were possibly related to study drug.'}], 'secondaryOutcomes': [{'measure': 'Composite Complete Remission Rate, CRc (complete remission + complete remission with incomplete blood count recovery + complete remission with incomplete platelet count recovery [CR + CRi + CRp])', 'timeFrame': '36 months', 'description': 'Response rate will be summarized by dose cohort and overall using the percent of patients in patient with AML'}, {'measure': 'Overall response rate (ORR, defined as Complete remission + Marrow CR + Partial remission + Hematologic Improvement (CR + mCR+ PR + HI)', 'timeFrame': '36 months', 'description': 'Response rate will be summarized by dose cohort and overall using the percent of patients in patients with MDS, CMML'}, {'measure': 'The pharmacokinetics of CFI-400945 will be assessed through AUC.', 'timeFrame': '36 months', 'description': 'Area under the plasma concentration (AUC) versus time curve from time 0 to time of least measurable concentration tabulated by dose group.'}, {'measure': 'To assess the pharmacokinetic profile of CFI-400945 through Cmax.', 'timeFrame': '36 months', 'description': 'Cmax will be assessed through the maximum measured plasma concentration occurring at Tmax tabulated by dose group.'}, {'measure': 'To assess the pharmacokinetic profile of CFI-400945 through T1/2.', 'timeFrame': '36 months', 'description': 'Elimination half life will be calculated and tabulated by dose group.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Polo-like kinase 4', 'PLK4', 'serine/threonine kinase Polo-like kinase 4', 'CFI-400945', '945', 'Polo-Like Kinase 4 inhibitors/antagonists', 'hematologic malignancies', 'PLK-4', 'UHN', 'University Health Network', 'Treadwell', 'Treadwell Therapeutics', 'Treadwell Tx'], 'conditions': ['Acute Myeloid Leukemia', 'Myelodysplastic Syndromes', 'Chronic Myelomonocytic Leukemia', 'AML', 'MDS', 'CMML']}, 'referencesModule': {'references': [{'pmid': '38114624', 'type': 'DERIVED', 'citation': 'Murphy T, Mason JM, Leber B, Bray MR, Chan SM, Gupta V, Khalaf D, Maze D, McNamara CJ, Schimmer AD, Schuh AC, Sibai H, Trus M, Valiquette D, Martin K, Nguyen L, Li X, Mak TW, Minden MD, Yee KWL. Preclinical characterization and clinical trial of CFI-400945, a polo-like kinase 4 inhibitor, in patients with relapsed/refractory acute myeloid leukemia and higher-risk myelodysplastic neoplasms. Leukemia. 2024 Mar;38(3):502-512. doi: 10.1038/s41375-023-02110-9. Epub 2023 Dec 19.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to test the safety of an investigational drug called CFI-400945 alone and in combination with azacitidine.', 'detailedDescription': 'This study will be evaluating the safety and tolerability of CFI-400945 in subjects with Acute Myeloid Leukemia, Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia. The study is designed to build on encouraging data from another study and to obtain further safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) data of CFI-400945.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Patients must be \\>18 years of age\n2. For Parts 1A and 1B, the following malignancy types will be included:\n\n 1. Relapsed or refractory AML.\n 2. MDS, after prior hypomethylating agents.\n 3. CMML, with progressive disease/lack of response after hypomethylating agents\n\n For Parts 1A and 1B, Patients may have relapsed or refractory disease.\n3. For Parts 2A and 2B, the following malignancy types will be included:\n\n 1. Relapsed or Refractory AML.\n 2. MDS patients should be limited to high risk disease\n 3. MDS or CMML should be previously untreated and patients with AML may have relapsed or refractory disease;\n4. Have clinically acceptable laboratory screening results (i.e., clinical chemistry, hematology, and urinalysis) within certain limits per protocol.\n5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n\nExclusion Criteria:\n\n1. Patients who have received investigational therapy, radiotherapy, immunotherapy, monoclonal antibodies, or chemotherapy within 14 days or 5 half-lives (whichever is shorter)\n2. Allogeneic or autologous transplant for AML with infusion of stem cells within 90 days before Cycle 1 Day 1, or on active immunosuppressive therapy for graft-versus-host disease (GVHD) or GVHD prophylaxis within 2 weeks of Cycle 1 Day 1.\n3. Any Grade ≥ 2 persistent non-hematological toxicity related to allogeneic transplant, such as those requiring systemic immunosuppressive therapy.'}, 'identificationModule': {'nctId': 'NCT04730258', 'acronym': 'TWT-202', 'briefTitle': 'A Study of CFI-400945 With or Without Azacitidine in Patients With AML, MDS or CMML', 'organization': {'class': 'INDUSTRY', 'fullName': 'Treadwell Therapeutics, Inc'}, 'officialTitle': 'Phase 1b/2 Clinical Study of the Safety, Tolerability, and Pharmacokinetic and Pharmacodynamic Profiles of CFI-400945 as a Single Agent or in Combination With Azacitidine in Patients With AML, MDS or CMML', 'orgStudyIdInfo': {'id': 'TWT-202'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': '1A: Monotherapy escalation and expansion', 'description': 'Dose escalation and expansion arm with CFI-400945', 'interventionNames': ['Drug: CFI-400945']}, {'type': 'EXPERIMENTAL', 'label': '2A: Combination escalation and expansion', 'description': 'Dose escalation and expansion arm with CFI-400945 and azacitidine', 'interventionNames': ['Drug: CFI-400945', 'Drug: Azacitidine']}], 'interventions': [{'name': 'CFI-400945', 'type': 'DRUG', 'otherNames': ['CFI-400945 fumarate', '945', '400945'], 'description': 'The starting dose is 32 mg/day for escalation arms and the recommended starting dose for the expansion arms.', 'armGroupLabels': ['1A: Monotherapy escalation and expansion', '2A: Combination escalation and expansion']}, {'name': 'Azacitidine', 'type': 'DRUG', 'description': 'Azacitidine will be given at its labeled dose and schedule', 'armGroupLabels': ['2A: Combination escalation and expansion']}]}, 'contactsLocationsModule': {'locations': [{'zip': '91010', 'city': 'Duarte', 'state': 'California', 'country': 'United States', 'facility': 'City of Hope', 'geoPoint': {'lat': 34.13945, 'lon': -117.97729}}, {'zip': '95817', 'city': 'Sacramento', 'state': 'California', 'country': 'United States', 'facility': 'University of California Davis Comprehensive Cancer Center', 'geoPoint': {'lat': 38.58157, 'lon': -121.4944}}, {'zip': '40207', 'city': 'Louisville', 'state': 'Kentucky', 'country': 'United States', 'facility': 'Norton Cancer Institute - Saint Matthews', 'geoPoint': {'lat': 38.25424, 'lon': -85.75941}}, {'zip': '10021', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'New York Presbyterian Weill Cornell Medical Center', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '43210', 'city': 'Columbus', 'state': 'Ohio', 'country': 'United States', 'facility': 'The Ohio State University Comprehensive Cancer Center', 'geoPoint': {'lat': 39.96118, 'lon': -82.99879}}, {'zip': '77030', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'The University of Texas MD Anderson Cancer Centre', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}, {'zip': 'T6G2B7', 'city': 'Edmonton', 'state': 'Alberta', 'country': 'Canada', 'facility': 'University of Alberta', 'geoPoint': {'lat': 53.55014, 'lon': -113.46871}}, {'zip': 'M5G2C1', 'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'facility': 'Princess Margaret Cancer Center', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}, {'city': 'Hong Kong', 'country': 'Hong Kong', 'facility': 'Queen Mary Hospital', 'geoPoint': {'lat': 22.27832, 'lon': 114.17469}}], 'overallOfficials': [{'name': 'Gautam Borthakur, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'The University of Texas MD Anderson Cancer Centre'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'It is too early to determine whether we will make IPD available - we do not yet have a process written on this. Field will be updated once our policy / process is written.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Treadwell Therapeutics, Inc', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}