Asciminib treatment optimization in ≥ 3rd line CML-CP

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

13 Oct 2021 → 25 Feb 2026

Decision date (initial)

2024-06-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-511381-36-00

EudraCT number

2020-006057-21

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy, Others

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.

Secondary objectives 15

1. To evaluate the safety and tolerability of asciminib in patients with CML-CP following 2 or more prior TKI treatments
2. 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
3. To assess the rate of MMR at week 48 for patients with MMR at baseline
4. To assess the time to MMR
5. To assess the rate of early responses of BCR-ABL1 ≤10% and ≤1% at weeks 12, 24, 36 and 48
6. To assess the rate of deep molecular responses (MR4 and MR4.5) at weeks 12, 24, 36, 48, 72, 96 and 144
7. To assess cytogenetic response (% Ph+ metaphases) at weeks 48 and EOT.
8. To characterize the impact of additional cytogenetic abnormalities on efficacy
9. To assess cumulative molecular responses by all-time points
10. To assess duration of MMR
11. To assess sustained deep molecular responses as prerequisite for Treatment Free Remission (TFR)
12. To assess rate of progressions (PFS)
13. To assess overall survival (OS)
14. To assess time to treatment failure (TTF)
15. To evaluate patient reported outcomes and quality of life by using MDASI-CML

Conditions and MedDRA coding

Chronic Myelogenous Leukemia in chronic phase (CML-CP)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Signed informed consent must be obtained prior to participation in the study
2. Male or female patients with a diagnosis of CML-CP ≥ 18 years of age
3. Treatment with a minimum of 2 or more prior TKIs (i.e. imatinib, nilotinib, dasatinib, bosutinib, radotinib or ponatinib)
4. Warning or failure (adapted from the 2020 ELN Recommendations) or intolerance to the most recent TKI therapy at the time of screening
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
6. Adequate end organ function (as per central laboratory tests)

Exclusion criteria 8

1. Known presence of the BCR-ABL1 T315I mutation at any time prior to study entry
2. Known second chronic phase of CML after previous progression to AP/BC
3. Previous treatment with a hematopoietic stem-cell transplantation
4. Patient planning to undergo allogeneic hematopoietic stem cell transplantation
5. Uncontrolled cardiac repolarization abnormality
6. 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
7. History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
8. History of ongoing active acute or chronic liver disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. MMR at 48 weeks

Secondary endpoints 15

1. Type, frequency and severity of adverse events, changes in laboratory values that fall outside the pre-determined ranges and clinically notable ECG and other safety data (vital signs, physical examination).
2. MMR rate at weeks 12, 24, 36, 72, 96 and 144.
3. MMR rate at week 48 for patients with MMR at baseline.
4. Time from the date of randomization to the date of first documented MMR
5. Rate of BCR-ABL1 ≤ 10% and ≤1% at weeks 12, 24, 36 and 48
6. Rate of MR4 and MR4.5 at weeks 12, 24, 36, 48, 72, 96 and 144.
7. Rate of complete cytogenetic response (CCyR) at weeks 48 and EOT.
8. Additional chromosomal abnormalities and occurrence of high-risk ACAs
9. Rate of BCR-ABL1 ≤ 10%, BCR-ABL1 ≤1%, MMR, MR4 and MR4.5 by all-time points.
10. Duration of MMR.
11. Duration of MR4 without loss of MMR.
12. Time from randomization to death.
13. Time from randomization to treatment failure defined as BCR-ABL1 > 1%.
14. Change in symptom burden and interference from baseline over time according to the MDASI-CML PRO instrument.
15. Time from randomization to the earliest occurrence of documented disease progression to AP/BC or death

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 14

Locations

7 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 58 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications