Asciminib as Initial Therapy for Patients With Chronic Myeloid Leukemia in Chronic Phase (ALERTCML)
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ClinicalTrials.gov Identifier: NCT05143840 |
Recruitment Status :
Recruiting
First Posted : December 3, 2021
Last Update Posted : March 26, 2024
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This study is a multicenter Phase 2, non-randomized, open-label single-group frontline study administering asciminib in patients with newly diagnosed Chronic Myeloid Leukemia-Chronic Phase (CML-CP). The aim of this study is to evaluate the efficacy and safety of asciminib in newly diagnosed CML-CP. Patients will receive asciminib 80 mg orally once daily during the single asciminib phase. Response is determined by PCR (polymerase chain reaction) blood test during the study. Patients who have not achieved a response after 24 months (but no later than 36 months) of single agent asciminib will be offered the addition of a low dose tyrosine kinase inhibitor (low-TKI) namely dasatinib, imatinib, or nilotinib at the investigator's discretion. The following doses of the TKIs will be used:
- Dasatinib 50 mg daily
- Imatinib 300 mg daily
- Nilotinib 300 mg daily
Patients will discontinue study treatment if they experience disease progression, or unacceptable toxicity.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Chronic Myeloid Leukemia, Chronic Phase Adult CML Leukemia, Myeloid Leukemia,Myeloid, Chronic | Drug: Asciminib Drug: Ascimininb + Nilotinib Drug: Asciminib + Imatinib Drug: Asciminib + Dasatinib | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 8 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Intervention Model Description: | Single group frontline asciminib |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Asciminib as Initial Therapy With Addition of Lower Dose Tyrosine Kinase Inhibitors for Patients With Chronic Myeloid Leukemia Who do Not Achieve a Deep Molecular Remission (ALERT CML) |
Actual Study Start Date : | April 22, 2022 |
Estimated Primary Completion Date : | February 2025 |
Estimated Study Completion Date : | February 2027 |
Arm | Intervention/treatment |
---|---|
Experimental: Asciminib
Asciminib 80mg taken orally once a day starting cycle 1 day 1 for up to 24 months during the single agent asciminib phase. Patients who have not achieved MR4.5 after 24 months will be given a low dose tyrosine kinase inhibitor (low-TKI). There will be three options of low-TKIs to be given at the investigator's discretion. |
Drug: Asciminib
Potent tyrosine kinase inhibitor that displays anti-tumor activity by specifically targeting the ABL myristate-binding pocket (STAMP).
Other Name: ABL001 Drug: Ascimininb + Nilotinib For subjects that do not achieve MR4.5 (molecular response) after 24 months of single-agent asciminib will be offered the addition of nilotinib 300mg, once daily, with the goal of attaining MR4.5.
Other Name: ABL001 + TASIGNA Drug: Asciminib + Imatinib For subjects that do not achieve MR4.5 (molecular response) after 24 months of single-agent asciminib will be offered the addition of imatinib 300mg, once daily, with the goal of attaining MR4.5.
Other Name: ABL001 + Gleevec Drug: Asciminib + Dasatinib For subjects that do not achieve MR4.5 (molecular response) after 24 months of single-agent asciminib will be offered the addition of dasatinib 50mg, once daily, with the goal of attaining MR4.5.
Other Name: ABL001 + Sprycel |
- Primary Outcome Measure 1: Deep Molecular Response [ Time Frame: 24 months ]This measure is the number of subjects in deep molecular response (DMR) defined as breakpoint cluster region ABL proto-oncogene 1 (BCR-ABL1) <0.0032% International Standard (IS) by real-time quantitative polymerase chain reaction (RT-PCR).
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age ≥18 years old
- Willing and able to give informed consent
- Newly diagnosed with CML in chronic phase within 6 months from confirmed diagnosis and have either the b3a2 (e14a2) or b2a2 (e13a2) variants that give rise to the p210 BCR::ABL1 protein. Subtype classification whether b3a2 (e14a2) or b2a2 (e13a2) is not required for study eligibility.
- Minimal prior CML therapy with a TKI for less than or equal to 30 days. Treatment with hydroxyurea, busulfan, anagrelide or other non-specific chemotherapy agents is allowed with no time restrictions within the eligible time from diagnosis.
- ECOG performance status 0-2 (appendix 1)
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Adequate organ function:
- AST and ALT < 3 times the institutional upper limit of normal (ULN)
- Creatinine < 1.5 times the institutional upper limit of normal
- Total bilirubin < 1.5 times the institutional ULN or < 3.0 x the institutional ULN with Gilbert Syndrome (unless direct bilirubin is within normal limits)
- Adequately controlled blood pressure, defined as systolic blood pressure of <140 mmHq and diastolic of <90 mmHg, at the time of enrollment.
- Serum lipase less than or equal to 1.5 x ULN. For serum lipase > ULN - less than or equal to 1.5 x ULN, value should be considered not clinically significant and not associated with risk factors for acute pancreatitis.
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Female patients must meet one of the following:
- Postmenopausal for at least one year before the screening visit,
- Surgically sterile
- If they are of childbearing potential, agree to practice two effective methods of contraception from the time of signing of the informed consent form through 90 days after the last dose of study drug,
- Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable contraception methods.)
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Male patients, even if surgically sterilized (i.e., status post vasectomy), must agree to one of the following:
- Practice effective barrier contraception during the entire study treatment period and through 90 days after the last study drug dose
- Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)
Exclusion Criteria:
- Patients with accelerated or blast phase CML (refer to appendix 4)
- Active second malignancy requiring active treatment
- History of recent (within 12 months) acute pancreatitis or chronic pancreatitis
- Subjects who have previously received treatment with asciminib.
- Subjects with PLT count < 50,000 mm3 or ANC of < 500 mm3 or Hemoglobin < 8 g/dL
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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 greater than or equal to 450 msec (male patients), greater than or equal to 460 msec (female patients) unless patient has a pacemaker
- Long QT syndrome, family history of idiopathic sudden death or congenital long
QT syndrome, or any of the following:
i. Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia ii. Concomitant medication(s) with a "Known risk of Torsades de Pointes" per wwwcrediblemeds.org/ that cannot be discontinued or replace 7 days prior to starting study drug by safe alternative medication. iii. Inability to determine the QTcF interval
- Pregnant or lactating
- Taking a strong inhibitors or inducers of CYP3A4 or CYP3A4 substrates with narrow therapeutic index (refer to appendix 6) at time of enrollment
- Unable to comply with lab appointment schedule and PRO assessments
- Another investigational drug within 4 weeks of enrollment
- Any serious medical or psychiatric illness that could, in the investigator's opinion, interfere with the completion of treatment according to this protocol
- Patient has undergone a prior allogeneic stem cell transplant
- Known clinical history of active HBV infection
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05143840
Contact: Kelly Jenkins, MSN, RN | 706-721-1206 | kejenkins@augusta.edu | |
Contact: GCC Clinical Trials Office | 706-721-2505 | Cancer_Center_Trials@augusta.edu |
United States, Georgia | |
Georgia Cancer Center at Augusta University | Recruiting |
Augusta, Georgia, United States, 30912 | |
Contact: Kelly Jenkins, MSN, RN 706-721-1206 kejenkins@augusta.edu | |
Contact 706-721-2505 Cancer_Center_Trials@augusta.edu | |
Principal Investigator: Jorge E. Cortes, MD | |
United States, Michigan | |
Karmanos Cancer Institute | Recruiting |
Detroit, Michigan, United States, 48201 | |
Contact: Sharon Prokop, RN, BSN 313-576-9369 prokops@karmanos.org | |
United States, New York | |
Roswell Park Comprehensive Cancer Center | Recruiting |
Buffalo, New York, United States, 14263 | |
Contact 716-845-7127 LeukResearch@roswellpark.org | |
Memorial Sloan Kettering Cancer Center | Recruiting |
New York, New York, United States, 10065 | |
Contact: Michael Mauro, MD 646-608-3744 MedLeukMauro@mskcc.org | |
Contact: Additional Contact Information 646-632-7847 maurom@mskcc.org | |
United States, Utah | |
Huntsman Cancer Institute | Recruiting |
Salt Lake City, Utah, United States, 84112 | |
Contact: Braxton Smith 801-213-8431 Braxton.Smith@hci.utah.edu | |
United States, Wisconsin | |
Froedtert Hospital & the Medical College of Wisconsin | Recruiting |
Milwaukee, Wisconsin, United States, 53226 | |
Contact: Ehab Atallah, MD 414-805-4600 eatallah@mcw.edu |
Principal Investigator: | Jorge Cortes, MD | Augusta University |
Responsible Party: | Augusta University |
ClinicalTrials.gov Identifier: | NCT05143840 |
Other Study ID Numbers: |
HJKC3-0004 CABL001AUS06T ( Other Identifier: Novartis Study Identifier ) |
First Posted: | December 3, 2021 Key Record Dates |
Last Update Posted: | March 26, 2024 |
Last Verified: | March 2024 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Chronic Myeloid Leukemia Adult CML tyrosine kinase inhibitors H. Jean Khoury Cure CML Consortium HJKC3-0004 |
Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Neoplasms by Histologic Type Neoplasms Hematologic Diseases Myeloproliferative Disorders Bone Marrow Diseases Chronic Disease Disease Attributes Pathologic Processes Niacinamide Imatinib Mesylate |
Dasatinib Nilotinib Asciminib Tyrosine Kinase Inhibitors Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Vitamin B Complex Vitamins Micronutrients Physiological Effects of Drugs |