Chronic Myelogenous Leukemia - Chronic Phase Clinical Trial
— ASC2ESCALATEOfficial title:
A Phase II Multicenter, Open-label, Single-arm Dose Escalation Study of Asciminib Monotherapy in 2nd and 1st Line Chronic Phase - Chronic Myelogenous Leukemia (ASC2ESCALATE)
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.
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. |
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 |
Lead Sponsor | Collaborator |
---|---|
Novartis Pharmaceuticals |
United States,
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 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Terminated |
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