ASSET-CML study

JRCT ID: jRCTs071230047

Registered date:27/07/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Chronic Myelogenous Leukemia-Chronic Phase
• Date of first enrollment: 09/08/2023
• Target sample size: 68
• Study type: Interventional

Intervention(s)

Asciminib (Scemblix) will be administered within the approved dosage and administration in Japan (the usual adult dosage is 40 mg of asciminib orally twice daily on an empty stomach. The dose will be reduced according to the patient's condition.
(1) Asciminib treatment for 24 months after DMR (MR4.5) is confirmed (including the period of achieving DMR prior to pre-registration).
(2) After confirming persistence of DMR (MR4.5) for 24 months, treatment is discontinued. BCR-ABL1 mRNA will be measured to confirm the presence of recurrence during the treatment discontinuation period.
(3) If MMR loss is confirmed after discontinuation of asciminib treatment, acsiminib is resumed at the dose prior to discontinuation.

Outcome(s)

• Primary Outcome: TFR rate at 12 months after discontinuation of asciminib treatment.

Secondary Outcome

(1) Indicators of protocol treatment efficacy.
- TFR rate at 24 months after discontinuation of asciminib treatment.
- Overall survivals.
(2) Remission rates (MR4.5 and MR4.0) at the time of re-administration due to MMR loss after discontinuation of asciminib treatment.
(3) Examination of factors associated with TFR.
- Total duration of TKI administration
- Total duration of TKI + asciminib administration
- Duration of DMR induction
- Total dose of asciminib during DMR (for 24 months)
- Duration from last discontinuation to relapse
- Peripheral blood marker expression profiles such as T/NK/Treg and lymphocyte subsets by flow cytometry
- Sokal score, Hasford score, ELTS score at the time of CML diagnosis
- Gender
(4) PRO (using the Japanese version of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3.0) attached to the study protocol).
(5) AEs during protocol treatment (after pre-registration).

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Pre-Registration Inclusion Criteria
Patients with Chronic Myelogenous Leukemia-Chronic Phase(CML-CP) who satisfy all of the following criteria.
(1) Patients without extramedullary leukemia, except for hepatomegaly and splenomegaly mass.
(2) Patients with molecular genetic relapse (MMR loss: BCR-ABL1 mRNA IS > 0.1% by RQ-PCR) despite discontinuation of Tyrosine Kinase Inhibitor(TKI) after achieving DMR (MR4.0 or MR4.5: BCR-ABL1 mRNA IS =<0.01% or =<0.0032% by RQ-PCR) of at least 1 year with 1st line or 2nd line or later TKI treatment.*1
*1) In principle, molecular relapse (loss of MMR) is the standard, but patients who restarted treatment due to loss of DMR at the discretion of a doctor are also included.
(3) Patients who have any of the following categories after criteria (2) above.
1) Patients who were treated with asciminib as the 3rd line or later, after resistance/intolerance to 2nd line or later TKI treatment.
2) Patients who were on TKI up to the 2nd line at criteria (2) above, and who were treated with asciminib as a 3rd line or later treatment at the discretion of the attending physician.
(4) Patients with DMR (MR4.5: BCR-ABL1 mRNA IS =<0.0032% by RQ-PCR) after criteria (3) above.
(5) Patients 18 years or older at pre-registration.
(6) Patients with ECOG PS score of 0-2.
(7) Patients who are judged by the investigator or sub-investigator that the functions of major organs (liver, kidneys and lungs) are maintained.
(8) Patients with written consent.

2. Official Registration Inclusion Criteria
(1) Patients who confirmed two consecutive DMR (MR4.5).
(2) Patients whose written consent was already obtained at pre-registration.

Exclude criteria

Patients who fall under any of the following criteria will not be selected as the subjects of this study.
(1) Patients with active double cancer.
(2) Patients who are in pregnancy or under breast feeding.
(3) Patients with a history of hypersensitivity to asciminib hydrochloride.
(4) Patients with a history of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis.
(5) Patients who are deemed to be ineligible for the study by the investigator or sub-investigator.

Related Information

• Primary Sponsor: Kimura Shinya
• Source(s) of Monetary Support: Novartis Pharma K.K.