E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Myelogenous Leukemia in chronic phase (CML-CP) |
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E.1.1.1 | Medical condition in easily understood language |
CML is a bone marrow cancer caused by a gene mutation which causes over growth of white blood cells. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009012 |
E.1.2 | Term | Chronic myelogenous leukemia |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to estimate the molecular response rate (MMR) of all the patients at week 48 with CML-CP following two or more prior TKI treatments and with no evidence of MMR at baseline. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of asciminib in patients with CML-CP following two or more prior TKI treatments. To assess the rate of MMR in patients without MMR at baseline and at alternative time points at weeks 12, 24, 36, 72, 96 and 144 To assess the rate of MMR at week 48 for patients with MMR at baseline To assess the time to MMR To assess the rate of early responses of BCR-ABL1 ≤10% and ≤1% at weeks 12, 24, 36 and 48 To assess the rate of deep molecular responses (MR4 and MR4.5) at weeks 12, 24, 36, 48, 72, 96 and 144 To assess cytogenetic response (% Ph+ metaphases) at weeks 48 and EOT. To characterize the impact of additional cytogenetic abnormalities on efficacy To assess cumulative molecular responses by all-time points To assess duration of MMR To assess sustained deep molecular responses as prerequisite for Treatment Free Remission (TFR) To assess rate of progressions (PFS) (Please refer to the protocol Table 2-1 for the full list) |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
'Single cell signaling and immune profiling sub-study to CABL001A2302' Anticipated start date: Oct 2021 Objectives: Identify features of single cell immune and signaling profiles early after initiating asciminib treatment that predict: BCR-ABL1 (IS) level at 48 weeks (MMR or not), the decrease of BCR-ABL (IS) level during the first 6 months, AEs and patient reported outcomes |
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E.3 | Principal inclusion criteria |
Male or female patients with a diagnosis of CML-CP ≥ 18 years of age Treatment with a minimum of 2 or more prior TKIs (i.e. imatinib, nilotinib, dasatinib, bosutinib, radotinib or ponatinib) Warning or failure (adapted from the 2020 ELN Recommendations) or intolerance to the most recent TKI therapy at the time of screening Adequate end organ function (as per central laboratory tests) Other protocol defined inclusion criteria may apply. |
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E.4 | Principal exclusion criteria |
Known presence of the BCR-ABL1 T315I mutation at any time prior to study entry Known history of AP/BC Previous treatment with a hematopoietic stem-cell transplantation Patient planning to undergo allogeneic hematopoietic stem cell transplantation Uncontrolled cardiac repolarization abnormality 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 History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis History of ongoing active acute or chronic liver disease Other protocol defined exclusion criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
Major Molecular Response (MMR) rate at week 48. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
MMR rate at weeks 12, 24, 36, 72, 96 and 144. MMR rate at week 48 for patients with MMR at baseline. Time from the date of randomization to the date of first documented MMR Rate of BCR-ABL1 ≤ 10% and ≤1% at weeks 12, 24, 36 and 48 Rate of MR4 and MR4.5 at weeks 12, 24, 36, 48, 72, 96 and 144. Rate of complete cytogenetic response (CCyR) at weeks 48 and EOT. Additional chromosomal abnormalities and occurrence of high-risk additional chromosomal abnormalities (ACAs) Rate of BCR-ABL1 ≤ 10%, BCR-ABL1 ≤1%, MMR, MR4 and MR4.5 by all-time points. Duration of MMR. Duration of MR4 without loss of MMR. Time from the date of randomization to the earliest occurrence of documented disease progression to AP/BC or the date of death from any cause. Time from randomization to death. Time from randomization to treatment failure define as BCR-ABL1 > 1%. Change in symptom burden and interference from baseline over time according to the MDASI-CML PRO instrument. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144/EOT. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, cytogenetics |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Brazil |
Canada |
Korea, Republic of |
Malaysia |
Oman |
Singapore |
Viet Nam |
Austria |
France |
Poland |
Spain |
Germany |
Greece |
Italy |
Russian Federation |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 6 |
E.8.9.2 | In all countries concerned by the trial years | 5 |