Frontline Asciminib Combination in Chronic Phase CML

NCT03906292 | Active Not Recruiting Phase 2

• 2 other identifiers: Fascination2024-516212-24-00
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 21

Brief Summary

Adult male and female patients with newly diagnosed Philadelphia chromosome positive (Ph+) and/or BCR-ABL1 positive CML can be included in the study until 3 months after diagnosis. A \<4 week pretreatment with hydroxyurea is permitted. Patients treated for \<6 weeks with nilotinib 300 mg BID, imatinib 400 mg QD, dasatinib 100 mg QD or without any therapy are eligible for recruitment and will be allocated to the respective cohort. All patients must provide written informed consent to be enrolled in the trial. Cohorts were designed to allow assessment of QD and BID asciminib based combinations to optimize quality of life and compliance. Patients will not be randomized. In general, cohorts will be filled consecutively. Asciminib therapy will be commenced 12 weeks after start of nilotinib, imatinib or dasatinib and after recovery of hematopoiesis or in case of no therapy so far 6 weeks after diagnosis as first line treatment. Referred patients already treated with imatinib, nilotinib or dasatinib will remain on the initial drug and will be allocated to the respective cohort.

Conditions

Chronic Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• deep molecular response (Rate of MR4)

  Achievement of deep molecular response (MR4) throught standardized testing of BCR-ABL-transcript Levels

  at month 12 after Start of Standard-Therapy

• deep molecular Response (Rate of MR4.5)

  Achievement of deep molecular response (MR4.5) throught standardized testing of BCR-ABL-transcript Levels

  at month 36 after Start of Standard-Therapy

Secondary Outcomes (6)

• molecular response (MMR and MR4.5)

  at and by 6, 12, 18, 24, 36 and 60 months after Start of Therapy

• Adverse Events

  at and by baseline, 3, 6, 12, 15, 18, 21, 24, 36 and 60 months after Start of Therapy

• Progression free survival

  at month 60 after Start of Therapy

• Overall survival

  at month 60 after Start of Therapy

• Maintenance of MR4.5 during Asciminib-monotherapy

  at month 36 and 60 after Start of Therapy

Study Arms (5)

Asciminib 60mg QD

EXPERIMENTAL

Standard therapy of Imatinib 400 mg QD and asciminib 60 mg QD

Drug: Imatinib; Drug: Asciminib

Asciminb 20 mg BID

EXPERIMENTAL

Standard therapy of Nilotinib 300 mg BID and asciminib 20 mg BID

Drug: Nilotinib 300 mg; Drug: Asciminib

Asciminib 40 mg QD

EXPERIMENTAL

Standard therapy of Nilotinib 300 mg BID and asciminib 40 mg QD

Drug: Nilotinib 300 mg; Drug: Asciminib

Asciminib 80 mg QD

EXPERIMENTAL

Standard therapy of Dasatinib 100 mg QD and asciminib 80 mg QD

Drug: Dasatinib; Drug: Asciminib

Asciminib 80 mg QD monotherapy

EXPERIMENTAL

Asciminib 80 mg QD as a single agent

Drug: Asciminib

Interventions

Imatinib DRUG

Imatinib 400 mg QD and asciminib 60 mg QD

Also known as: Imatinib 400 mg QD and asciminib 60 mg QD

Asciminib 60mg QD

Nilotinib 300 mg DRUG

Nilotinib 300 mg BID and asciminib 20 mg BID or 40 mg QD

Also known as: Nilotinib 300 mg BID and asciminib 20 mg BID or 40 mg QD

Asciminb 20 mg BID; Asciminib 40 mg QD

Dasatinib DRUG

Dasatinib 100 mg QD and asciminib 80 mg QD

Also known as: Dasatinib 100 mg QD and asciminib 80 mg QD

Asciminib 80 mg QD

Asciminib DRUG

Asciminib 80 mg QD Monotherapy

Asciminb 20 mg BID; Asciminib 40 mg QD; Asciminib 60mg QD; Asciminib 80 mg QD; Asciminib 80 mg QD monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients with diagnosis of CP-CML with cytogenetic confirmation of the Ph+ chromosome \[t(9;22)(q34;q11)\].
• Ph-negative cases or patients with variant translocations who are BCR-ABL1 positive in multiplex PCR 35 will be also considered eligible.
• ECOG performance status of ≤2.
• Age ≥ 18 years old (no upper age limit is given)
• Serum levels of potassium, magnesium, total calcium within the normal limits (≥LLN \[lower limit of normal\] and ≤ULN \[upper limit of normal\]). Correction of electrolytes levels with supplements to fulfil enrolment criteria is allowed.
• AST and ALT ≤2.5 x ULN or 5.0 x ULN if considered due to leukemia
• Alkaline phosphatase ≤2.5 x ULN unless considered due to leukemia
• Total bilirubin ≤1.5 x ULN, except known Gilbert disease
• Serum creatinine ≤2 x ULN
• Written informed consent prior to any study procedures being performed.

You may not qualify if:

• Allogeneic stem cell transplantation
• Known impaired cardiac function, including any of the following:
• Congenital long QT syndrome
• History of or presence of clinically significant ventricular or atrial tachyarrhythmia
• QTc \>450 msec on screening ECG
• Myocardial infarction within 12 months prior to starting therapy
• Other clinical significant heart disease (e.g. unstable angina, congestive heart failure)
• Acute or chronic viral hepatitis with moderate or severe hepatic impairment (Child-Pugh scores \>6), even if controlled
• Other concurrent uncontrolled medical conditions (e.g., active or uncontrolled infections, acute or chronic liver and renal disease) that could cause unacceptable safety risks or compromise compliance with the protocol
• Impaired gastrointestinal function or disease that may alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting and diarrhea, malabsorption syndrome, small bowel resection or gastric by-pass surgery)
• Concomitant medications known to be strong inducers or inhibitors of the CYP450 isoenzyme CYP3A4
• Patients who have undergone major surgery ≤2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
• Patients who are pregnant or breastfeeding or women of reproductive potential not employing an effective method of birth control. Women of childbearing potential must have a negative serum pregnancy test within 14 days of study start. Post-menopausal women must be amenorrheic for at least 12 months in order to be considered of non-childbearing potential. Male and female patients must agree to employ an effective method of birth control throughout the study and for up to 2 weeks following discontinuation of study drug
• Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
• Known serious hypersensitivity reactions to asciminib, imatinib, nilotinib or dasatinib

Sponsors & Collaborators

• University of Jena: lead
• Ludwig-Maximilians - University of Munich: collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (21)

Universitätsklinikum Aachen Medizinische Klinik IV

Aachen, 52074, Germany

Location

Charite Universitätsmeditin Berlin, Campus Virchow Klinikum

Berlin, 13353, Germany

Location

Universitätsklinikum Bonn

Bonn, 53105, Germany

Location

Klinikum Bremen Mitte

Bremen, 28177, Germany

Location

Klinikum Chemnitz gGmbH

Chemnitz, 09113, Germany

Location

GOKOS GmbH

Dresden, 01307, Germany

Location

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

Dresden, 01307, Germany

Location

Universitätsklinikum Erlangen

Erlangen, 91054, Germany

Location

Universitätsklinikum Essen

Essen, 45122, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt, 60590, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum Jena

Jena, 07747, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Gemeinschaftspraxis Dres. Müller/ Kröning/ Jentsch-Ullrich/ Tietze/ Krogel

Magdeburg, 39104, Germany

Location

Universitätsmedizin der Johannes- Gutenberg Universität Mainz

Mainz, 55131, Germany

Location

Universitätsmedizin Mannheim

Mannheim, 68169, Germany

Location

Universitätsklinikum Gießen und Marburg

Marburg, 35043, Germany

Location

Klinikum rechts der Isar

München, 81675, Germany

Location

Brüderkrankenhaus St. Josef Paderborn

Paderborn, 33098, Germany

Location

Krankenhaus Barmherzige Brüder Regensburg

Regensburg, 93049, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Imatinib Mesylate; asciminib; nilotinib; BID protein, human; Dasatinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Thiazoles; Sulfur Compounds; Azoles

Study Officials

• Thomas Ernst, Prof. Dr.

  University Hospital Jena

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 5 parallel cohorts

Study Record Dates

• First Submitted: December 14, 2018
• First Posted: April 8, 2019
• Study Start: August 19, 2019
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 10, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (21)