Sustained treatment-free period in the course of a disease when symptoms become less severe in BCR-ABL+ chronic myeloid leukemia: a prospective study comparing a drug called Nilotinib versus another called Imatinib with switch to Nilotinib in absence of optimal response.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Gimema Franco Mandelli Onlus

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

17 Oct 2016 → ongoing

Decision date (initial)

2024-07-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma · A.I.L. Associazione Italiana contro le leucemie · Fondazione Gimema Franco Mandelli Onlus

External identifiers

EU CT number

2023-510434-83-00

EudraCT number

2015-005248-33

ClinicalTrials.gov

NCT02602314

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

The study will investigate in newly diagnosed CP-CML patients the efficacy of NIL frontline therapy vs IM followed by a switch to NIL in the case of absence of an optimal response as defined by ELN criteria.

Secondary objectives 10

1. Monitoring the molecular response.
2. Progression-free survival (PFS) in the two arms of the study.
3. Overall Survival in the two arms of the study.
4. Rates of major molecular response (MR3.0) during the study in the two arms of the study
5. The dynamics of molecular response
6. The relationship between baseline characteristics and the primary objectives
7. The relationship between early molecular response and the primary objectives
8. To assess the safety profile of both arms.
9. To determine the rate and the time-distribution of the discontinuation causes of the first-line TKI
10. To investigate quality of life (QoL) differences between treatment arms over time

Conditions and MedDRA coding

Chronic Myeloid Leukemia (CML) in Chronic Phase (CP)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patients eligible for inclusion in this study have to meet all of the following criteria: • Patients with a confirmed diagnosis of BCR/ABL+ CML in chronic phase o Documented chronic phase CML must meet all the following criteria: 1. < 15% blasts in peripheral blood 2. < 30% blasts plus promyelocytes in peripheral blood 3. < 20% basophils in the peripheral blood 4. = 100 x 109/L (= 100,000/mm3) platelets
2. Age =18
3. ECOG performance status of 0-2
4. Evidence of typical BCR-ABL transcripts which are amenable to standardized RQ-PCR
5. Adequate end organ function as defined by: o Total bilirubin < 1.5 x ULN (ULN = upper limit of normal in a local institution lab). Does not apply to patients with isolated hyperbilirubinemia (e.g., Gilbert’s disease) grade < 3 o SGOT (AST) and SGPT (ALT) = 3 x ULN o Serum amylase and lipase = 2 x ULN o Alkaline phosphatase = 2.5 x ULN o Serum creatinine < 1.5 x ULN
6. Written informed consent prior to any study procedures.

Exclusion criteria 13

1. Previous treatment with BCR-ABL inhibitors for more than 30 days.
2. Expression of any atypical BCR-ABL transcripts, instead of the classical P210-encoding type with the e13a2 or the e14a2 junction at screening.
3. Previous anticancer agents (hydroxyurea, anagrelide, interferon) for CML for more than three months.
4. Poorly controlled diabetes mellitus (defined as HbA1c >8%
5. Prior documented history of coronary heart disease, including myocardial infarction, coronary bypass, coronary stent, and symptomatic angina as defined at page 30 in Exclusion Criteria.
6. Uncontrolled hypertension
7. History of peripheral arterial occlusive disease.
8. History of acute pancreatitis within 12 months of study entry, or a past medical history of chronic pancreatitis
9. Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers which cannot be either discontinued or switched to a different medication prior to starting study drug
10. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and for which cannot be either safely discontinued or switched to a different medication prior to starting study drug.
11. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment
12. Patients unable to understand and to comply with study instructions and requirements
13. Refusal to give informed consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. To evaluate the rates of molecular response (MR4.5) at 24 months
2. To evaluate the rates of molecular response (MR4.5) at 24 months - To evaluate the rate of patients who remain in sustained treatment free remission (=MR3.0) without molecular relapse 12 months after entering the TFR phase. The molecular relapse is defined as loss of MMR, or confirmed loss of MR3.0

Secondary endpoints 10

1. To determine the depth of molecular response by 4 years.
2. To estimate progression-free survival (PFS) in the two arms of the study at 60 months
3. To estimate the Overall Survival in the two arms of the study at 60 months
4. To determine the rates of major molecular response (MR3.0) at 1, 2, 3, and 4 year in the two arms of the study.
5. The dynamics of molecular response
6. The relationship between baseline characteristics and the achievement of MR4.5 (after treatment NIL frontline therapy vs IM followed by switch to NIL) and the sustained treatment free remission rate (=MR3.0);
7. The relationship between early molecular response and the achievement of MR4.5 (after treatment NIL frontline therapy vs IM followed by switch to NIL) and the sustained treatment free remission rate (=MR3.0)
8. To assess the safety profile of either NIL and IM arms
9. To determine the rate and the time-distribution of the discontinuation of the firstline TKI, for side-effects, toxicity and AEs.
10. To investigate quality of life (QoL) differences between treatment arms over time

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Gimema Franco Mandelli Onlus

Sponsor organisation

Fondazione Gimema Franco Mandelli Onlus

Address

Via Casilina 5

City

Rome

Postcode

00182

Country

Italy

Scientific contact point

Organisation

Fondazione Gimema Franco Mandelli Onlus

Contact name

GIMEMA Centro Dati

Public contact point

Organisation

Fondazione Gimema Franco Mandelli Onlus

Contact name

GIMEMA Centro Dati

Third parties 3

Locations

2 EU/EEA countries · 53 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 7 files

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

Application history

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