A clinical research study evaluating the possibility to stop the drug nilotinib (Tasigna) in chronic myeloid leukemia (CML) patients who have very small amount of leukemia cells remaining after nilotinib (Tasigna) treatment.

• Register: EUCTR
• Last refreshed on: 4 March 2013
• Main ID: EUCTR2012-003186-18-ES
• Date of registration: 29/11/2012
• Prospective Registration: Yes
• Primary sponsor: Novartis Farmacéutica S.A.
• Public title: A clinical research study evaluating the possibility to stop the drug nilotinib (Tasigna) in chronic myeloid leukemia (CML) patients who have very small amount of leukemia cells remaining after nilotinib (Tasigna) treatment.
• Scientific title: A phase II, single arm, open label study of treatment-free remission after achieving sustained MR4.5 on nilotinib - ENESTop
• Date of first enrolment: 19/02/2013
• Target sample size: 117
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-003186-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Argentina, Belgium, Brazil, Canada, France, Germany, Greece, Israel, Japan, Korea, Republic of, Poland, Russian Federation, Saudi Arabia, Spain, Tunisia, United States

Contacts

• Name: Javier Malpesa
• Affiliation: Novartis Farmacéutica S.A.

• Name: Javier Malpesa
• Affiliation: Novartis Farmacéutica S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
Patients eligible for inclusion in this study have to meet all of the following criteria:
1. Male or female patients ? 18 years of age
2. ECOG Performance Status of 0, 1, or 2
3. Patient with diagnosis of BCR-ABL positive CML
4. Patient has received a minimum of 3 years of tyrosine kinase inhibitor treatment (first with imatinib and then switched to nilotinib) since initial diagnosis
5. Patient has at least 2 years of nilotinib treatment prior to study entry.
6. Patient has achieved MR4.5 (local laboratory assessment) during nilotinib treatment, and determined by a Novartis designated central PCR lab assessment at screening
7. Adequate end organ function as defined in the protocol
8. Patients must have the following electrolyte values ? LLN (lower limit of normal) limits or corrected to within normal limits with supplements prior to the first dose of study medication as defined in the protocol.
9. Patients must have normal marrow function as defined in the protocol
10. Written informed consent obtained prior to any screening procedures
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 37

Exclusion criteria:
Patients eligible for this study must not meet any of the following criteria:
1. Prior AP, BC or allo-transplant
2. Patient has documented MR4.5 at the time when switched from imatinib to nilotinib
3. Patients with known atypical transcript
4. Mutation(s) detected if a testing was done in the past (there is no requirement to perform mutation testing at study entry if it was not done in the past)
5. Dose reductions due to neutropenia or thrombocytopenia in the past 6 months
6. Patient ever attempted to permanently discontinue imatinib or nilotinib treatment
7. Known impaired cardiac function as defined in the protocol
8. 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 (e.g. uncontrolled diabetes (defined as HbA1c > 9%), uncontrolled infection)
9. History of acute pancreatitis within 1 year prior to study entry or past medical history of chronic pancreatitis
10. Known presence of a significant congenital or acquired bleeding disorder unrelated to cancer
11. History of other active malignancy within 5 years prior to study entry with the exception of previous or concomitant basal cell skin cancer, previous cervical carcinoma in situ treated curatively
12. Patients who have not recovered from prior surgery
13. Treatment with other investigational agents (defined as not used in accordance with the approved indication) within 4 weeks of Day 1
14. Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to study entry.
15. Patients actively receiving therapy with herbal medicines that are strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to study entry.
16. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either safely discontinued or switched to a different medication prior to study entry.
17. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery)
18. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
19. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Ph+ chronic myeloid leukemia (CML)
MedDRA version: 14.1 Level: LLT Classification code 10054352 Term: Chronic phase chronic myeloid leukemia System Organ Class: 100000004864

Intervention(s)

Trade Name: Tasigna
Product Name: nilotinib
Product Code: AMN107
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: NILOTINIB
CAS Number: 641571-10-0
Current Sponsor code: AMN107
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Trade Name: Tasigna
Product Name: nilotinib
Product Code: AMN107
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: NILOTINIB
CAS Number: 641571-10-0
Current Sponsor code: AMN107
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Secondary Objective: - To evaluate the proportion of patients in TFR within 24, 36, and 48 months following nilotinib cessation
- To estimate progression-free survival (PFS) following nilotinib cessation
- To estimate treatment-free survival (TFS)
- To estimate overall survival (OS)
- To characterize the kinetics of BCR-ABL transcript after re-start of nilotinib therapy

Primary end point(s): No documented confirmed loss of MR4, no documented loss of MMR and no re-starting of nilotinib therapy in the first 12 months following nilotinib cessation. Confirmed loss of MR4 is two consecutive BCR-ABL > 0.01% International Standard. Loss of MMR does not require confirmation.

Main Objective: The purpose of this study is to determine the rate of successful treatment-free remission (TFR) within the first 12 months following cessation of treatment in patients who achieved and maintained a molecular response (MR) 4.5 on nilotinib after a switch from imatinib. TFR phase is often referred to as discontinuation phase in other studies.

Timepoint(s) of evaluation of this end point: Within the first 12 months following cessation of treatment.

Secondary Outcome(s)

Secondary end point(s): - No documented confirmed loss of MR4, no documented loss of MMR and no re-starting of nilotinib therapy in the first 24, 36, and 48 months following nilotinib cessation. Confirmed loss of MR4 is two consecutive BCR-ABL > 0.01% IS. Loss of MMR does not require any confirmation
- To estimate progression-free survival (PFS) following nilotinib cessation: Progression to AP/BC or death where the ?failure? event is the earliest occurrence of the following event: progression to AP/BC or death from any cause.
- To estimate treatment-free survival (TFS): TFS is defined as lack of any of the following events: loss of MMR, confirmed loss of MR4, re-start of nilotinib treatment, progression to AP/BC or death from any cause.
- To estimate overall survival (OS): OS is defined as the time from the date of cessation of nilotinib therapy to the date of death from any cause.
To characterize the kinetics of BCR-ABL transcript after re-start of nilotinib therapy: BCR-ABL transcript changes within 12 months after re-start of nilotinib therapy

Timepoint(s) of evaluation of this end point: as indicated in the protocol

Secondary ID(s)

CAMN107A2408

Source(s) of Monetary Support

Novartis Pharma Services AG