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Asciminib as Initial Therapy for Patients With Chronic Myeloid Leukemia in Chronic Phase

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ClinicalTrials.gov Identifier: NCT05143840
Recruitment Status : Recruiting
First Posted : December 3, 2021
Last Update Posted : July 18, 2022
Sponsor:
Collaborator:
H. Jean Khoury Cure CML Consortium
Information provided by (Responsible Party):
Augusta University

Brief Summary:
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 orally twice daily. Response is determined by PCR (polymerase chain reaction) blood test during the study. Patients who have not achieved a response after 24 months of single agent asciminib will be offered the addition of nilotinib. Nilotinib will be started at 300 mg BID in addition to asciminib if indicated. 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 Phase 2

Detailed Description:

Asciminib is a potent allosteric inhibitor of BCR-ABL1 oncogene that confers resistance to tyrosine kinase inhibitors (TKIs). Asciminib has potential to combine with TKIs to prevent the emergence of BCR-ABL1 mutations, increasing the depth of molecular response in CML-CP patients. Anticipated enrollment is 50 subjects across sites.

Primary Objective:

To estimate the proportion of patients with previously untreated CML-CP attaining deep molecular response (PCR blood test).

Secondary Objectives:

  1. To estimate the proportion of patients achieving molecular response at specific time points
  2. To estimate the time to molecular response
  3. To evaluate the duration of hematologic and molecular response to asciminib
  4. To define the time to progression and overall survival for patients with CML in early CP treated with asciminib
  5. To evaluate the safety profile of asciminib in patients with CML-CP
  6. To evaluate the development of ABL mutations for patients with CML in early CP treated with asciminib
  7. To analyze differences in response rates and in prognosis within different risk groups and patient characteristics
  8. To evaluate patient-reported outcomes in patients with CML receiving asciminib
  9. To investigate treatment-free remission after at least 2 years of sustained deep molecular remission for patients receiving single agent asciminib

Exploratory objectives:

  1. To evaluate the safety and efficacy of concomitant use of nilotinib with asciminib in patients who have not achieved MR4.5.
  2. To evaluate the rate of successful treatment discontinuation for patients using the combination of asciminib and nilotinib
  3. Evaluate the role of Digital droplet PCR (ddPCR) in predicting TFR
  4. Evaluating the correlation between the gene expression signature of patients and the chances of achieving MMR and DMR
  5. Evaluate whether B, NK and T cells DNA mutation and RNA expression are relevant and whether they can predict response in patients with CML using single cell analysis.

Subjects must meet all inclusion criteria and none of the exclusion criteria of the study. No enrollment waivers will be granted. After successful screening, subjects will be enrolled and treatment will start within 7 days of enrollment. Eligible subjects will begin asciminib on cycle 1 day 1 of the trial. After 2 years, subjects will be offered the addition of taking nilotinib with asciminib if a molecular response is not met (PCR blood test).

Duration of each participant is expected to take approximately 5 years.

Regimen Description Study Drug Dose Route Schedule Cycle Length Asciminib 40 mg Oral Twice a day (BID) 4 weeks (28 days) Nilotinib 300 mg* Oral Twice a day (BID) 4 weeks (28 days)

*Nilotinib will be taken if indicated at a maximum dose of 300mg BID

Dose levels and dose modifications of the study drugs will be made per protocol.

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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 for Patients With Chronic Myeloid Leukemia in Chronic Phase
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 40mg taken orally twice a day starting cycle 1 day 1 for up to 24 months.
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, twice daily, with the goal of attaining MR4.5.




Primary Outcome Measures :
  1. 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).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥18 years old
  2. Willing and able to give informed consent
  3. 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-ABL protein. Subtype classification whether b3a2 (e14a2) or b2a2 (e13a2) is not required for study eligibility.
  4. Minimal prior CML therapy including a TKI for less than 30 days.
  5. ECOG performance status 0-2 (appendix 1)
  6. Adequate organ function:

    1. AST and ALT < 3 times the institutional upper limit of normal
    2. Creatinine < 1.5 times the institutional upper limit of normal
    3. Total bilirubin < 1.5 times the institutional upper limit of normal or < 3.0 x the institutional upper limit of normal with Gilbert Syndrome (unless direct bilirubin is within normal limits)
  7. Female patients must meet one of the following:

    1. Postmenopausal for at least one year before the screening visit,
    2. Surgically sterile
    3. 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,
    4. Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable
    5. 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.)
  8. Male patients, even if surgically sterilized (i.e., status post vasectomy), must agree to one of the following:

    1. Practice effective barrier contraception during the entire study treatment period and through 90 days after the last study drug dose
    2. Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable
    3. 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:

  1. Patients with accelerated or blast phase CML (refer to appendix 4)
  2. Active second malignancy requiring active treatment
  3. History of recent (within 12 months) acute pancreatitis or chronic pancreatitis
  4. Subjects who have previously received treatment with asciminib.
  5. Subjects with PLT count < 50,000 mm3 or ANC of < 500 mm3 or Hemoglobin < 8 g/dL
  6. Lipase > institutional upper limit of normal
  7. Pregnant or lactating
  8. Taking a strong inhibitors or inducers of CYP3A4 or CYP3A4 substrates with narrow therapeutic index (refer to appendix 6) at time of enrollment
  9. Unable to comply with lab appointment schedule and PRO assessments
  10. Another investigational drug within 4 weeks of enrollment
  11. Any serious medical or psychiatric illness that could, in the investigator's opinion, interfere with the completion of treatment according to this protocol
  12. Patient has undergone a prior allogeneic stem cell transplant
  13. Screening 12-lead ECG showing a baseline corrected QT interval >480msec (patients with a pacemaker will still be eligible with QTc>500msec)

Information from the National Library of Medicine

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


Contacts
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Contact: Kelly Jenkins, MSN, RN 706-721-1206 kejenkins@augusta.edu
Contact: GCC Clinical Trials Office 706-721-2505 Cancer_Center_Trials@augusta.edu

Locations
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United States, Georgia
Georgia Cancer Center at Augusta University Not yet 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, Wisconsin
Froedtert Hospital & the Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Ehab Atallah, MD    414-805-4600    eatallah@mcw.edu   
Sponsors and Collaborators
Augusta University
H. Jean Khoury Cure CML Consortium
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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: July 18, 2022
Last Verified: July 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Augusta University:
Chronic Myeloid Leukemia
Adult CML
tyrosine kinase inhibitors
H. Jean Khoury Cure CML Consortium
HJKC3-0004
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases