Study Description
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.
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.
Interventions
asciminib
Eligibility Criteria
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):
Signed informed consent must be obtained prior to participation in the study
CML-CP, no previous AP or BC
≥ 18 years of age
ECOG performance status of 0, 1 or 2
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:
Previous treatment
With 2 or more ATP-binding site TKIs (for 2L patient cohort)
More than 4 weeks with 1-ATP-binding site TKIs (for 1L patient cohort)
Previous treatment with asciminib
Known presence of the T315I mutation at any time prior to study entry
Known second chronic phase of CML after previous progression to AP/BC
Previous treatment with a hematopoietic stem-cell transplantation
Patient planning to undergo allogeneic hematopoietic stem cell transplantation
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
History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
Participation in a prior investigational study within 30 days prior to randomization or within 5 half-lives of the investigational product, whichever is longer
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
Pregnant or nursing (lactating) women
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.
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).
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).
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.
Known hypersensitivity to the study treatment.
Study Location
Manhattan Hematol Oncol Associates
Recruiting
New York,Alec Goldenberg,10016 - New York,United States
Virginia Cancer Specialists
Recruiting
Gainesville,Mitul Gandhi,20155 - Virginia,United States
Siteman Cancer Center .
Recruiting
Saint Louis,Camille N Abboud,63110 - Missouri,United States
Ctr For Cancer And Blood Disorders
Recruiting
Fort Worth,(817-759-7030) -- Latha Polavaram,76104 - Texas,United States
Houston Methodist Hospital
Recruiting
Houston,(346-238-5685) -- Shilpan Shah,77030 - Texas,United States
University Missouri Ellis Fischel Cancer Center
Recruiting
Columbia,(573-882-4979) -- Hildebrandt Gerhard,65203 - Missouri,United States
Novant Health Heart and Vascular Institute .
Recruiting
Charlotte,James Dugan,28204 - North Carolina,United States
Care Access Research Clifton
Recruiting
Clifton,Richards Afjonja,07013 - New Jersey,United States
Texas Oncology, P.A.
Recruiting
Austin,(512-324-7991) -- Jason M Melear,78121 - Texas,United States
Florida Cancer Specialists-North
Recruiting
Saint Petersburg,(+1 727 216 1143) -- Gustavo Adolfo Fonseca,33705 - Florida,United States
Mays Cancer Center
Recruiting
San Antonio,(210-450-1887) -- Zohra Nooruddin,78229 - Texas,United States
Virginia K Crosson Cancer Center
Recruiting
Fullerton,Steven Kim,92835 - California,United States
St Vincent Frontier Cancer Center
Recruiting
Billings,(406-238-6962) -- Patrick Cobb,59102 - Montana,United States
Dana Farber Cancer Center .
Recruiting
Boston,Marlise Luskin,02215 - Massachusetts,United States
Huntsman Cancer Institute .
Recruiting
Salt Lake City,Srinivas Tantravahi,84112 - Utah,United States
University of Alabama at Birmingham .
Recruiting
Birmingham,Omer Jamy,35233-0271 - Alabama,United States
City Of Hope Atlanta
Recruiting
Atlanta,Sabarish Ayyappan,30033 - Georgia,United States
NYU Langone Long Island
Recruiting
Mineola,Kiner-Strachan Bonnie,11501 - New York,United States
The Stamford Hospital
Recruiting
Stamford,(203-358-8879) -- Kelsey Sokol,06904 - Connecticut,United States
Franciscan Health Indianapolis
Recruiting
Indianapolis,John Edwards,42637 - Indiana,United States
Alaska Oncology and Hematology
Recruiting
Anchorage,(907-279-3155) -- Steven Liu,99508 - Alaska,United States
Medical College of Wisconsin
Recruiting
Milwaukee,(414-805-5249) -- Ehab Atallah,53226 - Wisconsin,United States
Virginia Oncology Associates VOA - Lake Wright
Recruiting
Norfolk,(757-213-5637) -- Celeste Bremer,23502 - Virginia,United States
Dartmouth Hitchcock Medical Center
Recruiting
Lebanon,(603-650-6228) -- Swaroopa Yerrabothala,03756 - New Hampshire,United States
SUNY Stony Brook Medical Oncology
Recruiting
Stony Brook,(516-444-7863) -- Michael A. Schuster,11794-8174 - New York,United States
University of Kentucky
Recruiting
Lexington,(859-218-5151) -- Reinhold Munker,40536 - Kentucky,United States
Investigative Clinicl Rsrch of Indi
Recruiting
Indianapolis,Brian Mulherin,46260 - Indiana,United States
City of Hope National Medical
Recruiting
Duarte,(+16262564673#85013) -- Paul Koller,91010 - California,United States
Onco Inst of Hope and Innovation
Recruiting
Cerritos,(+1 562 698 6888) -- Arati Rani Chand,90703 - California,United States
Thomas Jefferson University
Recruiting
Philadelphia,(215-955-2432) -- Lindsay Wilde,19107 - Pennsylvania,United States
Fred Hutch Cancer Research
Recruiting
Seattle,(206-667-5000) -- Vivian Oehler,98109 - Washington,United States
Wake Forest Uni Health Sci Oncology
Recruiting
Winston-Salem,(336-716-7972) -- Bayard L. Powell,27157 - North Carolina,United States
Augusta University Georgia .
Recruiting
Augusta,(404-778-1900) -- Jorge Cortes,30912 - Georgia,United States
Nebraska Hematology-Oncology, P.C.
Recruiting
Lincoln,(402-484-4908) -- Kailash Mosalpuria,68506 - Nebraska,United States
Duke University Medical Center .
Recruiting
Durham,Lindsay Rein,27710 - North Carolina,United States
SUNY Upstate Medical Center
Recruiting
Syracuse,(315-464-4353) -- Teresa C Gentile,13210 - New York,United States
UNM
Recruiting
Albuquerque,Charles Foucar,87102 - New Mexico,United States
Jackson Onc Associates
Recruiting
Jackson,Thomas Williamson,39216 - Mississippi,United States
City of Hope Phoenix
Recruiting
Scottsdale,Schriber Jeffrey,85258 - Arizona,United States
Oregon Health Sciences University .
Recruiting
Portland,Michael Charles Heinrich,97239 - Oregon,United States
Hackensack Meridian Health Research
Recruiting
Edison,Evan Naylor,88837 - New Jersey,United States
UCLA
Recruiting
Los Angeles,Gary Schiller,90095 - California,United States
Wichita Community Clcl Onco Program Oncology
Recruiting
Wichita,Shaker R Dakhil,67214 - Kansas,United States
Avera Cancer Avera Cancer Institute
Recruiting
Sioux Falls,(605-322-3291) -- Xavier Andrade-Gonzalez,57105 - South Dakota,United States
New York Bld And Cancer Specialists
Recruiting
Port Jefferson Station,Richard Zuniga,11776 - New York,United States
Emory University School of Medicine/Winship Cancer Institute
Recruiting
Atlanta,(404-686-2505) -- Anthony Michael Hunter,30308 - Georgia,United States
Texas Oncology Northeast Texas
Recruiting
Tyler,(903-579-9867) -- Habte Yimer,75702 - Texas,United States
Louisiana State University Main Centre
Recruiting
Shreveport,(318-675-5960) -- Poornima Ramadas,71130 - Louisiana,United States
USO Arizona Oncology
Recruiting
Tucson,Manda Sudhir,85711 - Arizona,United States
Clinical Research Alliance Research
Recruiting
Lake Success,(+1 516 488 2918#183) -- James D Olimpio,11042 - New York,United States
Rocky Mountain Cancer Centers USOR
Recruiting
Boulder,(303-385-2000) -- David J Andorsky,80304 - Colorado,United States
Hackensack University Medical Ctr
Recruiting
Hackensack,(201-996-5900) -- James McCloskey,07601 - New Jersey,United States
UCSF Fresno Internal Medicine
Recruiting
Fresno,(599-499-6566) -- Haifaa Abdulhaq,93701 - California,United States
Northwest Georgia Oncology Center .
Recruiting
Marietta,(770-281-5124) -- Steve McCune,30060 - Georgia,United States
Baptist MD Anderson Cancer Center
Recruiting
Jacksonville,(614-657-1463) -- Maxim Norkin,32207 - Florida,United States
Florida Cancer Specialists
Recruiting
Fort Myers,(239-274-9930) -- Blessy Jacob,33901 - Florida,United States
Texas Oncology San Antonio TO San Antonio
Recruiting
San Antonio,John Renshaw,78258 - Texas,United States
Lundquist Inst BioMed at Harbor .
Recruiting
Torrance,Sarah Tomassetti,90509-2910 - California,United States
VA Puget Sound Health Care System
Recruiting
Seattle,(800-329-8387) -- Robert Richard,98108 - Washington,United States
Rutgers Cancer Institute of New Jersey
Recruiting
New Brunswick,(732-235-6031) -- Dale Schaar,08903 - New Jersey,United States
Community Cancer Trials of Utah
Recruiting
Ogden,(801-689-3909) -- Carl Gray,84405 - Utah,United States
Hematology Oncology Care
Recruiting
Cincinnati,(513-751-2273) -- Kruti Patel,45236 - Ohio,United States
Uni of North Carolina Hospital
Recruiting
Chapel Hill,(919-966-4131) -- Josh Zeidner,27514 - North Carolina,United States
Northwest Medical Specialties
Recruiting
Tacoma,(253-428-8756) -- Frank Senecal,98405 - Washington,United States
Bon Secours Cancer Center
Recruiting
Greenville,(+1 864 603 6214) -- Robert David Siegel,29607 - South Carolina,United States
Texas Oncology TX Oncology Baylor
Recruiting
Dallas,(+1 214 370 1000) -- Moshe Yair Levy,75251 - Texas,United States
Florida Cancer Specialists East
Recruiting
Stuart,Shachar Peles,34994 - Florida,United States
Worldwide Contacts
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