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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05384587
Other study ID # CABL001AUS08
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date November 11, 2022
Est. completion date February 26, 2027

Study information

Verified date June 2024
Source Novartis
Contact Novartis Pharmaceuticals
Phone 1-888-669-6682
Email john.sabo@novartis.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This will be a multicenter Phase II open-label study of asciminib in CML-CP patients who have been previously treated with one prior ATP- binding site TKI with discontinuation due to treatment failure, warning or intolerance. (2L patient cohort). In addition, newly diagnosed CML-CP patients who may have received up to 4 weeks of prior TKI are included in a separate 1L patient cohort.


Description:

This trial consists of three periods: screening and baseline for up to 28 days, active treatment for up to 104 weeks and a safety follow up period for 30 days. Ninety-two (92) 2L patients with CML-CP without T315I mutation who had 1 prior ATP-binding site TKI discontinued due to treatment failure, warning or intolerance will be considered for the current study. Patients will be tested at screening for the T315I mutation and excluded if the mutation is found. To gain additional insights into the effect of asciminib in the 1L setting, an additional cohort of newly diagnosed CML-CP patients will be enrolled in the study. Based on the number of participating sites, it is approximated that between 60 and 90 patients could be enrolled. Enrollment of the 1L cohort will be stopped when a maximum of 90 patients have been enrolled or when approximately 60 patients have been enrolled and the 2L cohort is fully recruited, whichever comes first. Informed consent will be obtained before any procedures are performed for the study including eligibility assessments. All eligible patients will be initially treated with asciminib at 80 mg QD. At 6 months of study treatment, patients who have achieved BCR-ABL1IS ≤1% will continue on the same dose whereas those who have not will increase dose to 200mg QD. At 12 months of study treatment, patients will be evaluated for the primary endpoint of the study (MMR at 12 month in 2L patient cohort) and will pursue one of the following: - Continue on the current dose of asciminib if MMR is achieved - Increase dose to 200 mg QD if on 80 mg QD dosing and MMR is not achieved - Increase dose to 200 mg BID if on 200 mg QD dosing and MMR is not achieved - Take the patient off the study and switch to Investigator's agent of choice if MMR is not achieved and it is in the interest of the patient based on investigator's clinical judgment of prospect treatment benefit.


Recruitment information / eligibility

Status Recruiting
Enrollment 182
Est. completion date February 26, 2027
Est. primary completion date February 27, 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Key Inclusion Criteria: Participants eligible for inclusion in this study must meet the following criteria: Criteria #1-5 are common to both patient cohorts (2L and 1L): 1. Signed informed consent must be obtained prior to participation in the study 2. CML-CP, no previous AP or BC 3. = 18 years of age 4. ECOG performance status of 0, 1 or 2 5. Adequate end organ function within 14 days before the first dose of asciminib treatment. Patients with mild to moderate renal and hepatic impairment are eligible if: - Total bilirubin = 3.0 x ULN without AST/ALT increase - Aspartate transaminase (AST) = 5.0 x ULN - Alanine transaminase (ALT) = 5.0 x ULN - Serum lipase = 1.5 x ULN. For serum lipase > ULN and = 1.5 x ULN, value should be considered not clinically significant and not associated with risk factors for acute pancreatitis - Alkaline phosphatase = 2.5 x ULN - Creatinine clearance = 30 mL/min as calculated using Cockcroft- Gault formula Criteria #6 and 7 are specific to the 2L patient cohort 6. Warning or failure (according to 2020 ELN Recommendations; Hochhaus et al) to 1L TKI therapy at the time of screening a. Warning is defined as: i. Six months after the initiation of treatment: BCR- ABL1IS >1-10% ii. Twelve months after the initiation of treatment: BCR- ABL1IS >0.1-1% b. Treatment failure/resistance to 1L TKI is defined as: i. BCR-ABL1IS >10% if 1L treatment duration between 6 and 12 months ii. BCR-ABL1IS >1% if 1L treatment longer than 12 months treatment: loss of MMR 7. Beyond 12 months after the initiation of to 1L TKI, a. BCR-ABL1IS > 0.1% at screening b. Intolerance is defined as: i. Non-hematologic intolerance: Patients with grade 3 or 4 toxicity while on therapy, or with persistent grade 2 toxicity, unresponsive to optimal management, including dose adjustments (unless dose reduction is not considered in the best interest of the patient if response is already suboptimal) ii. Hematologic intolerance: Patients with grade 3 or 4 toxicity (absolute neutrophil count [ANC] or platelets) while on therapy that is recurrent after dose reduction to the lowest doses recommended by manufacturer Criteria #8 is specific to the 1L patient cohort 8. Patients with newly diagnosed CML-CP (treatment with a prior TKI (imatinib, or nilotinib, or dasatinib or bosutinib) for = 4 weeks is allowed) Key Exclusion Criteria: 1. Previous treatment 1. With 2 or more ATP-binding site TKIs (for 2L patient cohort) 2. More than 4 weeks with 1-ATP-binding site TKIs (for 1L patient cohort) 2. Previous treatment with asciminib 3. Known presence of the T315I mutation at any time prior to study entry 4. Known second chronic phase of CML after previous progression to AP/BC 5. Previous treatment with a hematopoietic stem-cell transplantation 6. Patient planning to undergo allogeneic hematopoietic stem cell transplantation 7. Cardiac or cardiac repolarization abnormality, including any of the following: - History within 6 months prior to starting study treatment of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG) - Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block) - QTcF at screening =450 msec (male patients), =450 msec (female patients) - Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: - Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia - Concomitant medication(s) with a "Known risk of Torsades de Pointes" per www.crediblemeds.org that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication - Inability to determine the QTcF interval 8. History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis 9. Participation in a prior investigational study within 30 days prior to randomization or within 5 half-lives of the investigational product, whichever is longer 10. Treatment with medications that meet one of the following criteria is not allowed and should be switched to an alternative at least one week prior to the start of treatment with study treatment: - Strong inducers of CYP3A for patients on the dose of 80 mg QD and 200mg QD - Strong inducers and inhibitors of CYP3A for patients on the dose of 200 mg BID 11. Pregnant or nursing (lactating) women 12. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception. Highly effective contraception for women should be maintained throughout the study and for at least 7 days after the last dose. 13. Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 7 days after stopping study (only for patients treated with asciminib). 14. Severe and/or uncontrolled concurrent medical disease that in the opinion of the Investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes, active or uncontrolled infection; uncontrolled arterial or pulmonary hypertension, uncontrolled clinically significant hyperlipidemia). 15. History of other active malignancy within 3 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively. 16. Known hypersensitivity to the study treatment.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
asciminib
Supplied in 40 mg tablets for oral use to be taken daily. Dose may be increased at 6 and 12 months based on molecular response with BCR-ABL1 Polymerase Chain Reaction testing.

Locations

Country Name City State
United States UNM Albuquerque New Mexico
United States Alaska Oncology and Hematology Anchorage Alaska
United States City Of Hope Atlanta Atlanta Georgia
United States Emory University School of Medicine/Winship Cancer Institute Atlanta Georgia
United States Augusta University Georgia . Augusta Georgia
United States Texas Oncology P A Austin Texas
United States St Vincent Frontier Cancer Center Billings Montana
United States University of Alabama at Birmingham . Birmingham Alabama
United States Dana Farber Cancer Center . Boston Massachusetts
United States Rocky Mountain Cancer Centers USOR Boulder Colorado
United States Onco Inst of Hope and Innovation Cerritos California
United States Uni of North Carolina Hospital Chapel Hill North Carolina
United States Novant Health Heart and Vascular Institute . Charlotte North Carolina
United States Hematology Oncology Care Cincinnati Ohio
United States Care Access Research Clifton Clifton New Jersey
United States University Missouri Ellis Fischel Cancer Center Columbia Missouri
United States Texas Oncology TX Oncology Baylor Dallas Texas
United States Henry Ford Hospital Detroit Michigan
United States City of Hope National Medical Duarte California
United States Duke University Medical Center . Durham North Carolina
United States Care Access Research Easton Pennsylvania
United States Hackensack Meridian Health Research Edison New Jersey
United States Florida Cancer Specialists Fort Myers Florida
United States Ctr For Cancer And Blood Disorders Fort Worth Texas
United States UCSF Fresno Internal Medicine Fresno California
United States Virginia K Crosson Cancer Center Fullerton California
United States Virginia Cancer Specialists Gainesville Virginia
United States Bon Secours Cancer Center Greenville South Carolina
United States Hackensack University Medical Ctr Hackensack New Jersey
United States Houston Methodist Hospital Houston Texas
United States Univ of TX MD Anderson Cancer Cntr Houston Texas
United States Franciscan Health Indianapolis Indianapolis Indiana
United States Investigative Clinicl Rsrch of Indi Indianapolis Indiana
United States Jackson Onc Associates Jackson Mississippi
United States Baptist MD Anderson Cancer Center Jacksonville Florida
United States Clinical Research Alliance Research Lake Success New York
United States Dartmouth Hitchcock Medical Center Lebanon New Hampshire
United States University of Kentucky Lexington Kentucky
United States Nebraska Hematology Oncology P C Lincoln Nebraska
United States UCLA Los Angeles California
United States Dean Health System Madison Wisconsin
United States Northwest Georgia Oncology Center . Marietta Georgia
United States Medical College of Wisconsin Milwaukee Wisconsin
United States NYU Langone Long Island Mineola New York
United States Rutgers Cancer Institute of New Jersey New Brunswick New Jersey
United States Manhattan Hematol Oncol Associates New York New York
United States Mt Sinai Medical Center New York New York
United States Virginia Oncology Associates VOA - Lake Wright Norfolk Virginia
United States Community Cancer Trials of Utah Ogden Utah
United States Thomas Jefferson University Philadelphia Pennsylvania
United States UPMC Pittsburgh Pennsylvania
United States New York Bld And Cancer Specialists Port Jefferson Station New York
United States Oregon Health Sciences University . Portland Oregon
United States Virginia Cancer Institute Richmond Virginia
United States Siteman Cancer Center . Saint Louis Missouri
United States Florida Cancer Specialists-North Saint Petersburg Florida
United States Huntsman Cancer Institute . Salt Lake City Utah
United States Mays Cancer Center San Antonio Texas
United States Texas Oncology San Antonio TO San Antonio San Antonio Texas
United States City of Hope Phoenix Scottsdale Arizona
United States Fred Hutch Cancer Research Seattle Washington
United States VA Puget Sound Health Care System Seattle Washington
United States Louisiana State University Main Centre Shreveport Louisiana
United States Avera Cancer Avera Cancer Institute Sioux Falls South Dakota
United States The Stamford Hospital Stamford Connecticut
United States SUNY Stony Brook Medical Oncology Stony Brook New York
United States Florida Cancer Specialists East Stuart Florida
United States SUNY Upstate Medical Center Syracuse New York
United States Northwest Medical Specialties Tacoma Washington
United States Lundquist Inst BioMed at Harbor . Torrance California
United States USO Arizona Oncology Tucson Arizona
United States Texas Oncology Northeast Texas Tyler Texas
United States Wichita Community Clcl Onco Program Oncology Wichita Kansas
United States Wake Forest Uni Health Sci Oncology Winston-Salem North Carolina

Sponsors (1)

Lead Sponsor Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other To investigate MR2, MR4, MR4.5 rate at visit MR2, MR4 and MR4.5 at all scheduled data collection time points except for MR4.5 at 24 month Baseline up to 24 months
Primary Percentage of participants who achieve Major Molecular Response (MMR) in the 2L setting MMR is defined as BCR-ABL1IS = 0.1%). Baseline up to 12 months
Secondary Percentage of participants achieving Molecular Response (MR4.5) Molecular response (MR) will be assessed. The rate of MR4.5 where MR4.5 is defined as a = 4.5 log reduction in BCR-ABL1 transcripts compared to the standardized baseline equivalent to = 0.0032% BCR-ABL1/ABL % by international scale as measured by real time Polymerase Chain Reaction (PCR). Baseline up to 24 months
Secondary Number of Adverse Events and Serious Adverse Events Clinically significant findings for vitals, laboratory values and electrocardiogram (ECG) will be reported as adverse events and or serious adverse events as determined by the investigator. Baseline up to 24 months
Secondary MMR Rate - All scheduled time points Percentage of participants who achieve MMR at or before the specified visit, i.e., if a patient achieves an MMR but then loses it before or at the visit, h/she will still be considered as achieving MMR by that time point. Baseline up to 3, 6, 18, and 24 months
Secondary Time to MMR Time to MMR is defined and calculated as date of first documented MMR - start date of study treatment +1 day. Baseline up to 24 months
Secondary Duration of MMR Duration of MMR is defined as the time from the date of first documented MMR to the earliest date of loss of MMR, progression to Accelerated Phase (AP) or Blast Crisis (BC), or CML-related death. Baseline up to 24 months
Secondary Time to Treatment Failure (TTF) Time to treatment failure (TTF) is defined as the time from date of randomization to an event of treatment failure. Baseline up to 24 months
Secondary Progression Free Survival (PFS) Time from the first dose of study treatment to the earliest occurrence of documented progression to Accelerated Phase (AP) or Blast Crisis (BC) or the date of death from any cause, before the end of the treatment phase. Baseline up to 24 months
Secondary Overall Survival (OS) Time from the first dose of study treatment to death due to any cause during the study. Baseline up to 24 months.
Secondary MR2 Rate - All scheduled time points Percentage of participants who achieve MR2 (defined as a = 2 log reduction in BCR-ABL1 transcripts) at or before the specified visit, i.e., if a patient achieves an MMR but then loses it before or at the visit, h/she will still be considered as achieving MR2 by that time point. Baseline up to 3, 6, 12, 18, and 24 months
Secondary MR4 Rate - All scheduled time points Percentage of participants who achieve MR4 (defined as a = 4 log reduction in BCR-ABL1 transcripts) at or before the specified visit, i.e., if a patient achieves an MMR but then loses it before or at the visit, h/she will still be considered as achieving MR4 by that time point. Baseline up to 3, 6, 12, 18, and 24 months
Secondary MR4.5 Rate - All scheduled time points Percentage of participants who achieve MR4.5 (defined as a = 4.5 log reduction in BCR-ABL1 transcripts) at or before the specified visit, i.e., if a patient achieves an MMR but then loses it before or at the visit, h/she will still be considered as achieving MR4.5 by that time point. Baseline up to 3, 6, 12, and 18
See also
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Recruiting NCT06082804 - Evaluation of Advanced Practice Nurse's Management of Patients With Chronic Myeloid Leukemia N/A
Active, not recruiting NCT04666259 - Asciminib in Monotherapy for Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and Without T315I Mutation Phase 3
Completed NCT04925141 - A Study of Dasatinib as First-line Treatment for Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia (CML-CP) Phase 4
Recruiting NCT05794880 - MCW Alpha/Beta T-Cell and B-Cell Depletion With Targeted ATG Dosing N/A
Recruiting NCT03842696 - Vorinostat for Graft vs Host Disease Prevention in Children, Adolescents and Young Adults Undergoing Allogeneic Blood and Marrow Transplantation Phase 1/Phase 2