Myeloproliferative Neoplasms Clinical Trial

Asciminib Monotherapy, With Dose Escalation, for 2nd and 1st Line Chronic Myelogenous Leukemia

Summary

This study will be a single arm multicenter Phase II open-label, dose escalation study of asciminib in patients with leukemia-cml/" >CML-CP without T315I mutation who have had 1 prior TKIs for which they did not respond to treatment or were intolerant to treatment.

View Full Description

Full 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.

View Eligibility Criteria

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 is for people with:

Myeloproliferative Neoplasms

Phase:

Phase 2

Estimated Enrollment:

182

Study ID:

NCT05384587

Recruitment Status:

Recruiting

Sponsor:

Novartis Pharmaceuticals

Check Your Eligibility

Let’s see if you might be eligible for this study.

What is your age and gender ?

Submit

There are 67 Locations for this study

See Locations Near You

University of Alabama at Birmingham .
Birmingham Alabama, 35233, United States More Info
Omer Jamy
Principal Investigator
Alaska Oncology and Hematology
Anchorage Alaska, 99508, United States More Info
Contact
907-279-3155
Steven Liu
Principal Investigator
City of Hope Phoenix
Scottsdale Arizona, 85258, United States More Info
Schriber Jeffrey
Principal Investigator
USO Arizona Oncology
Tucson Arizona, 85711, United States More Info
Manda Sudhir
Principal Investigator
Onco Inst of Hope and Innovation
Cerritos California, 90703, United States More Info
Arati Rani Chand
Principal Investigator
City of Hope National Medical
Duarte California, 91010, United States More Info
Paul Koller
Principal Investigator
UCSF Fresno Internal Medicine
Fresno California, 93701, United States More Info
Contact
599-499-6566
Haifaa Abdulhaq
Principal Investigator
Virginia K Crosson Cancer Center
Fullerton California, 92835, United States More Info
Steven Kim
Principal Investigator
UCLA
Los Angeles California, 90095, United States More Info
Gary Schiller
Principal Investigator
Lundquist Inst BioMed at Harbor .
Torrance California, 90509, United States More Info
Sarah Tomassetti
Principal Investigator
Rocky Mountain Cancer Centers USOR
Boulder Colorado, 80304, United States More Info
Contact
303-385-2000
David J Andorsky
Principal Investigator
The Stamford Hospital
Stamford Connecticut, 06904, United States More Info
Contact
203-358-8879
Kelsey Sokol
Principal Investigator
Florida Cancer Specialists
Fort Myers Florida, 33901, United States More Info
Contact
239-274-9930
Blessy Jacob
Principal Investigator
Baptist MD Anderson Cancer Center
Jacksonville Florida, 32207, United States More Info
Contact
614-657-1463
Maxim Norkin
Principal Investigator
Florida Cancer Specialists-North
Saint Petersburg Florida, 33705, United States More Info
Gustavo Adolfo Fonseca
Principal Investigator
Florida Cancer Specialists East
Stuart Florida, 34994, United States More Info
Shachar Peles
Principal Investigator
City Of Hope Atlanta
Atlanta Georgia, 30033, United States More Info
Sabarish Ayyappan
Principal Investigator
Emory University School of Medicine/Winship Cancer Institute
Atlanta Georgia, 30308, United States More Info
Contact
404-686-2505
Anthony Michael Hunter
Principal Investigator
Augusta University Georgia .
Augusta Georgia, 30912, United States More Info
Contact
404-778-1900
Jorge Cortes
Principal Investigator
Northwest Georgia Oncology Center .
Marietta Georgia, 30060, United States More Info
Contact
770-281-5124
Steve McCune
Principal Investigator
Franciscan Health Indianapolis
Indianapolis Indiana, 42637, United States More Info
John Edwards
Principal Investigator
Investigative Clinicl Rsrch of Indi
Indianapolis Indiana, 46260, United States More Info
Brian Mulherin
Principal Investigator
Wichita Community Clcl Onco Program Oncology
Wichita Kansas, 67214, United States More Info
Shaker R Dakhil
Principal Investigator
University of Kentucky
Lexington Kentucky, 40536, United States More Info
Contact
859-218-5151
Reinhold Munker
Principal Investigator
Louisiana State University Main Centre
Shreveport Louisiana, 71130, United States More Info
Contact
318-675-5960
Poornima Ramadas
Principal Investigator
Dana Farber Cancer Center .
Boston Massachusetts, 02215, United States More Info
Marlise Luskin
Principal Investigator
Jackson Onc Associates
Jackson Mississippi, 39216, United States More Info
Thomas Williamson
Principal Investigator
University Missouri Ellis Fischel Cancer Center
Columbia Missouri, 65203, United States More Info
Contact
573-882-4979
Hildebrandt Gerhard
Principal Investigator
Siteman Cancer Center .
Saint Louis Missouri, 63110, United States More Info
Camille N Abboud
Principal Investigator
St Vincent Frontier Cancer Center
Billings Montana, 59102, United States More Info
Contact
406-238-6962
Patrick Cobb
Principal Investigator
Nebraska Hematology-Oncology, P.C.
Lincoln Nebraska, 68506, United States More Info
Contact
402-484-4908
Kailash Mosalpuria
Principal Investigator
Dartmouth Hitchcock Medical Center
Lebanon New Hampshire, 03756, United States More Info
Contact
603-650-6228
Swaroopa Yerrabothala
Principal Investigator
Care Access Research Clifton
Clifton New Jersey, 07013, United States More Info
Richards Afjonja
Principal Investigator
Hackensack Meridian Health Research
Edison New Jersey, 88837, United States More Info
Evan Naylor
Principal Investigator
Hackensack University Medical Ctr
Hackensack New Jersey, 07601, United States More Info
Contact
201-996-5900
James McCloskey
Principal Investigator
Rutgers Cancer Institute of New Jersey
New Brunswick New Jersey, 08903, United States More Info
Contact
732-235-6031
Dale Schaar
Principal Investigator
UNM
Albuquerque New Mexico, 87102, United States More Info
Charles Foucar
Principal Investigator
Clinical Research Alliance Research
Lake Success New York, 11042, United States More Info
James D Olimpio
Principal Investigator
NYU Langone Long Island
Mineola New York, 11501, United States More Info
Kiner-Strachan Bonnie
Principal Investigator
Manhattan Hematol Oncol Associates
New York New York, 10016, United States More Info
Alec Goldenberg
Principal Investigator
New York Bld And Cancer Specialists
Port Jefferson Station New York, 11776, United States More Info
Richard Zuniga
Principal Investigator
SUNY Stony Brook Medical Oncology
Stony Brook New York, 11794, United States More Info
Contact
516-444-7863
Michael A. Schuster
Principal Investigator
SUNY Upstate Medical Center
Syracuse New York, 13210, United States More Info
Contact
315-464-4353
Teresa C Gentile
Principal Investigator
Uni of North Carolina Hospital
Chapel Hill North Carolina, 27514, United States More Info
Contact
919-966-4131
Josh Zeidner
Principal Investigator
Novant Health Heart and Vascular Institute .
Charlotte North Carolina, 28204, United States More Info
James Dugan
Principal Investigator
Duke University Medical Center .
Durham North Carolina, 27710, United States More Info
Lindsay Rein
Principal Investigator
Wake Forest Uni Health Sci Oncology
Winston-Salem North Carolina, 27157, United States More Info
Contact
336-716-7972
Bayard L. Powell
Principal Investigator
Hematology Oncology Care
Cincinnati Ohio, 45236, United States More Info
Contact
513-751-2273
Kruti Patel
Principal Investigator
Oregon Health Sciences University .
Portland Oregon, 97239, United States More Info
Michael Charles Heinrich
Principal Investigator
Thomas Jefferson University
Philadelphia Pennsylvania, 19107, United States More Info
Contact
215-955-2432
Lindsay Wilde
Principal Investigator
Bon Secours Cancer Center
Greenville South Carolina, 29607, United States More Info
Robert David Siegel
Principal Investigator
Avera Cancer Avera Cancer Institute
Sioux Falls South Dakota, 57105, United States More Info
Contact
605-322-3291
Xavier Andrade-Gonzalez
Principal Investigator
Texas Oncology, P.A.
Austin Texas, 78121, United States More Info
Contact
512-324-7991
Jason M Melear
Principal Investigator
Texas Oncology TX Oncology Baylor
Dallas Texas, 75251, United States More Info
Moshe Yair Levy
Principal Investigator
Ctr For Cancer And Blood Disorders
Fort Worth Texas, 76104, United States More Info
Contact
817-759-7030
Latha Polavaram
Principal Investigator
Houston Methodist Hospital
Houston Texas, 77030, United States More Info
Contact
346-238-5685
Shilpan Shah
Principal Investigator
Univ of TX MD Anderson Cancer Cntr
Houston Texas, 77030, United States More Info
Contact
713-792-2828
Koji Sasaki
Principal Investigator
Mays Cancer Center
San Antonio Texas, 78229, United States More Info
Contact
210-450-1887
Zohra Nooruddin
Principal Investigator
Texas Oncology San Antonio TO San Antonio
San Antonio Texas, 78258, United States More Info
John Renshaw
Principal Investigator
Texas Oncology Northeast Texas
Tyler Texas, 75702, United States More Info
Contact
903-579-9867
Habte Yimer
Principal Investigator
Community Cancer Trials of Utah
Ogden Utah, 84405, United States More Info
Contact
801-689-3909
Carl Gray
Principal Investigator
Huntsman Cancer Institute .
Salt Lake City Utah, 84112, United States More Info
Srinivas Tantravahi
Principal Investigator
Virginia Cancer Specialists
Gainesville Virginia, 20155, United States More Info
Mitul Gandhi
Principal Investigator
Virginia Oncology Associates VOA - Lake Wright
Norfolk Virginia, 23502, United States More Info
Contact
757-213-5637
Celeste Bremer
Principal Investigator
VA Puget Sound Health Care System
Seattle Washington, 98108, United States More Info
Contact
800-329-8387
Robert Richard
Principal Investigator
Fred Hutch Cancer Research
Seattle Washington, 98109, United States More Info
Contact
206-667-5000
Vivian Oehler
Principal Investigator
Northwest Medical Specialties
Tacoma Washington, 98405, United States More Info
Contact
253-428-8756
Frank Senecal
Principal Investigator
Medical College of Wisconsin
Milwaukee Wisconsin, 53226, United States More Info
Contact
414-805-5249
Ehab Atallah
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Myeloproliferative Neoplasms

Phase:

Phase 2

Estimated Enrollment:

182

Study ID:

NCT05384587

Recruitment Status:

Recruiting

Sponsor:


Novartis Pharmaceuticals

How clear is this clinincal trial information?

×

Introducing, the Journey Bar

Use this bar to access information about the steps in your cancer journey.