Asciminib in Monotherapy for Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and Without T315I Mutation

Completed · Phase 3

Conditions studied: Chronic Myelogenous Leukemia - Chronic Phase

In brief

This study was a multicenter Phase IIIb open-label, three-cohort study of asciminib in patients with CML-CP without T315I mutation who have had at least 2 prior TKIs and CML-CP harboring the T315I mutation with at least 1 prior TKI

Key facts

Study ID

NCT04666259

Run by

Novartis Pharmaceuticals

People needed

56

Starts

2021-05-25

Expected to finish

2024-06-26

Last updated by the study team

2025-10-16

Who can join

Age: 18 and older, up to 99. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants eligible for inclusion in this study must meet all of the following criteria:
• Written informed consent must be obtained and signed prior to participation in the study
• Male or female patients with a diagnosis of CML-CP ≥ 18 years of age
• Patients must meet all of the following laboratory values at the screening visit:
• < 15% blasts in peripheral blood and/or bone marrow
• < 30% blasts plus promyelocytes in peripheral blood and/or bone marrow
• < 20% basophils in the peripheral blood
• ≥ 50 x 109/L (≥ 50,000/ mm3) platelets
• Transient prior therapy related thrombocytopenia (< 50,000/mm3 for ≤ 30 days prior to screening) is acceptable
• No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
• Mutation Analysis testing performed 6 months before study entry
• Prior treatment with a minimum of:
• 2 prior ATP-site TKIs (i.e. imatinib, nilotinib, bosutinib, dasatinib or ponatinib) in case of absence of T315I mutation
• 1 prior ATP site TKI (i.e. imatinib, nilotinib, bosutinib, dasatinib or ponatinib) in case of presence of T315I mutation
• Failure (adapted from the 2020 ELN Recommendations) or intolerance to the most recent TKI therapy at the time of screening
• Failure for CML-CP patients (CP at the time of initiation of last therapy) is defined as meeting at least one of the following criteria.
• Three months after the initiation of therapy: >10% BCR-ABL1 on International Scale (IS) if confirmed within 1-3 months
• Six months after the initiation of therapy: BCR-ABL1 ratio > 10% IS
• Twelve months after initiation of therapy: BCR-ABL1 ratio > 1% IS
• At any time after the initiation of therapy, loss of CHR, MR2
• At any time after the initiation of therapy, the development of new BCR-ABL1 mutations which potentially cause resistance to current treatment
• At any time 12 months after the initiation of therapy, BCR-ABL1 ratio ≥ 1% IS or loss of MMR
• At any time after the initiation of therapy, new clonal chromosome abnormalities in Ph+ cells: CCA/Ph+
• Intolerance is defined as:
• 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)

You may not qualify if…

• Patients eligible for this study must not meet any of the following criteria:
• Known second chronic phase of CML after previous progression to AP/BC
• Previous treatment with a 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), ≥460 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 wwwcrediblemeds.org/ that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication.
• Inability to determine the QTcF interval
• 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, pulmonary hypertension)
• History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
• Known presence of significant congenital or acquired bleeding disorder unrelated to cancer
• 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
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery)
• Previous treatment with or known/ suspected hypersensitivity to asciminib or any of its excipients.
• Participation in a prior investigational study within 30 days prior to randomization or within 5 half-lives of the investigational product, whichever is longer
• 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 methods include:
• Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
• Female sterilization (have had surgical bilateral oophorectomy (with or without hysterectomy) total hysterectomy or bilateral tubal ligation at least six weeks before taking study treatment). In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
• Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that subject.
• Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception.

Where it is running

• Alaska Oncology and Hematology — Anchorage, Alaska, United States
• Arizona Oncology Associates — Phoenix, Arizona, United States
• Cancer Treatment Centers of America — Phoenix, Arizona, United States
• Pacific Shores Medical Group — Long Beach, California, United States
• Lundquist Inst BioMed at Harbor — Torrance, California, United States
• Rocky Mountain Cancer Centers — Boulder, Colorado, United States
• Memorial Cancer Institute — Hollywood, Florida, United States
• Florida Cancer Specialists — Sarasota, Florida, United States
• Florida Cancer Specialists-North — St. Petersburg, Florida, United States
• Florida Cancer Specialists East — Stuart, Florida, United States
• Florida Cancer Specialists Pan — Tallahassee, Florida, United States
• Indiana Blood and Marrow Institute — Beech Grove, Indiana, United States
• University of Kentucky — Lexington, Kentucky, United States
• Uni of Massachusetts Medical Center — Worcester, Massachusetts, United States
• Michigan Med University of Michigan — Ann Arbor, Michigan, United States
• Siteman Cancer Center — St Louis, Missouri, United States
• Cancer Institute of New Jersey — New Brunswick, New Jersey, United States
• Wake Forest University Baptist Medical Center — Winston-Salem, North Carolina, United States
• Uni of Cincinnati Medical Center — Cincinnati, Ohio, United States
• Oncology Hematology Care Inc — Cincinnati, Ohio, United States
• Northwest Cancer Specialists — Portland, Oregon, United States
• Texas Oncology — Dallas, Texas, United States
• Texas Oncology P A — Fort Worth, Texas, United States
• Univ of TX MD Anderson Cancer Cntr — Houston, Texas, United States
• Texas Oncology Northeast Texas — Tyler, Texas, United States

Full record on ClinicalTrials.gov

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