Treatment-free Remission After Achieving Sustained MR4.5 on Nilotinib (ENESTop)

A Phase II, Single Arm, Open Label Study of Treatment-free Remission in Chronic Myeloid Leukemia (CML) Chronic Phase (CP) Patients After Achieving Sustained MR4.5 on Nilotinib

ClinicalTrials.gov Identifier: NCT01698905

Novartis Reference Number: CAMN107A2408

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

A clinical research study to find out if it is safe to stop the drug nilotinib (Tasigna) in chronic myeloid leukemia (CML) patients. Patients who started treatment with imatinib (Gleevec) when they were first diagnosed with CML, then switched to nilotinib (Tasigna) for at least 2 years with the combined time on imatinib (Gleevec) and nilotinib (Tasigna) for at least 3 years and have very small amount of leukemia cells remaining after the nilotinib (Tasigna) treatment will qualify for the study.

Condition 
Chronic Myeloid Leukemia
Phase 
Phase 2
Overall status 
Active, not recruiting
Enrollment count 
163 participants
Start date 
Dec 20, 2012
Completion date 
Feb 06, 2025
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
nilotinib
Nilotinib will be labeled as AMN107 and supplied as 150 mg and/or 200 mg hard gelatin capsule. Nilotinib will not be dosed by weight or body surface area. Nilotinib will be administered orally at 300 mg twice daily (BID) or 400 mg BID, at approximately 12 hour intervals, and must not be taken with food. The capsules should be swallowed whole with water. No food should be consumed for at least 2 hours before the dose is taken and no additional food should be consumed for at least one hour after the dose is taken. Patients who were previously treated with 400 mg BID, and required subsequent permanent dose reduction to 400 mg QD will be allowed to enter this study on the same dose, 400 mg once daily.

Eligibility Criteria

Inclusion Criteria:

Male or female patients >= 18 years of age
ECOG Performance Status of 0, 1, or 2
Patient with diagnosis of BCR-ABL positive CML CP
Patient has received a minimum of 3 years of tyrosine kinase inhibitor treatment (first with imatinib (> 4 weeks) and then switched to nilotinib) since initial diagnosis
Patient has at least 2 years of nilotinib treatment prior to study entry.
Patient has achieved MR4.5 (local laboratory assessment) during nilotinib treatment, and determined by a Novartis designated central PCR lab assessment at screening

Adequate end organ function as defined by:

Direct bilirubin ≤ 1.5 x ULN except for i) patient with documented Gilbert's syndrome for whom any bilirubin value is allowed and ii) for patients with asymptomatic hyperbilirubinemia (liver transaminases and alkaline phosphatase within normal range)
SGOT(AST) and SGPT(ALT) < 3 x ULN (upper limit of normal)
Serum lipase ≤ 2 x ULN
Alkaline phosphatase ≤ 2.5 x ULN
Serum creatinine < 1.5 x ULN

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:

Potassium
Magnesium
Total calcium (corrected for serum albumin)

Patients must have normal marrow function as defined below:

Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
Platelets ≥ 100 x 109/L
Hemoglobin ≥ 9.0 g/dL
Written informed consent obtained prior to any screening procedures

Exclusion Criteria:

Prior AP, BC or allo-transplant
Patient has documented MR4.5 at the time when switched from imatinib to nilotinib
Patients with known atypical transcript
CML treatment resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V) 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)
Dose reductions due to neutropenia or thrombocytopenia in the past 6 months
Patient ever attempted to permanently discontinue imatinib or nilotinib treatment

Known impaired cardiac function including any one of the following:

Inability to determine the QT interval on ECG
Complete left bundle branch block
Long QT syndrome or a known family history of long QT syndrome
History of or presence of clinically significant ventricular or atrial tachyarrhythmias
Clinically significant resting bradycardia
QTcF > 480 msec
History or clinical signs of myocardial infarction within 1 year prior to study entry
History of unstable angina within 1 year prior to study entry
Other clinically significant heart disease (e.g. uncontrolled congestive heart failure or uncontrolled hypertension)
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)
History of acute pancreatitis within 1 year prior to study entry or past medical history of chronic pancreatitis
Known presence of a significant congenital or acquired bleeding disorder unrelated to cancer
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
Patients who have not recovered from prior surgery
Treatment with other investigational agents (defined as not used in accordance with the approved indication) within 4 weeks of Day 1
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. See Appendix 14.1 for a list of these medications. This list may not be comprehensive.
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. These herbal medicines may include Echinacea, (including E. purpurea, E. angustifolia and E. pallida), Piperine, Artemisinin, St. John's Wort, and Ginkgo.
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. (Please see www.azcert.org/medical-pros/drug-lists/printable-drug-list.cfm for a list of agents that prolong the QT interval.)
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)
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.

Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must have a negative serum pregnancy test before initiation of study treatment and must also use highly effective methods of contraception while enrolled in the study. The use of highly effective contraception should continue for at least 14 days after the last dose of study treatment or until the last day of TFR/TFR-2, or for the duration of a monthly cycle of oral contraception, whichever is longer. Acceptable forms of highly effective contraception methods include:

a. Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception and male/female sterilization defined as:

Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed and documented by follow up hormone level assessment
Male sterilization (at least 6 months prior to screening). For female patients on the study, study participation assumes the vasectomized male partner is the sole partner for that patient or b. A combination of any two of the following (i+ii or i+iii or ii+iii): i) Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository ii) Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception iii) Placement of an intrauterine device (IUD) or intrauterine system (IUS)

Study Locations

United States
USC Kenneth Norris Comprehensive Cancer Center USC
-
Los Angeles, 90033
California
United States
Indiana Blood and Marrow Institute SC
-
Beech Grove, 46107
Indiana
United States
St. Agnes Hospital SC
-
Baltimore, 21229
Maryland
United States
University of Texas Medical Branch SC
-
Galveston, 77555-1188
Texas
United States
Compass Oncology
-
Vancouver, 98683
Washington
United States
Argentina
Novartis Investigative Site
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Caba, C1221ADC
Buenos Aires
Argentina
Novartis Investigative Site
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Buenos Aires, C1114AAN
-
Argentina
Australia
Novartis Investigative Site
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Adelaide, 5000
South Australia
Australia
Novartis Investigative Site
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Box Hill, 3128
Victoria
Australia
Belgium
Novartis Investigative Site
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Antwerp, 2060
-
Belgium
Brazil
Novartis Investigative Site
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Goiania, 74605-050
GO
Brazil
Novartis Investigative Site
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Belo Horizonte, 30130-100
MG
Brazil
Novartis Investigative Site
-
Rio de Janeiro, 20.211-030
RJ
Brazil
Novartis Investigative Site
-
Rio De Janiero, 20231-050
RJ
Brazil
Novartis Investigative Site
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Porto Alegre, 90035-003
RS
Brazil
Novartis Investigative Site
-
Campinas,
SP
Brazil
Canada
Novartis Investigative Site
-
Hamilton, L8V 5C2
Ontario
Canada
Novartis Investigative Site
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Toronto, M5G 2M9
Ontario
Canada
Novartis Investigative Site
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Montreal, H1T 2M4
Quebec
Canada
Novartis Investigative Site
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Quebec, G1J 1Z4
-
Canada
France
Novartis Investigative Site
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Bordeaux, 33076
-
France
Novartis Investigative Site
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Grenoble, 38043
-
France
Novartis Investigative Site
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Lyon Cedex, 69373
-
France
Novartis Investigative Site
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Strasbourg cedex, 67085
-
France
Novartis Investigative Site
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Vandoeuvre les Nancy, 54511
-
France
Germany
Novartis Investigative Site
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Mannheim, 68305
Baden-Wuerttemberg
Germany
Novartis Investigative Site
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Berlin, 13353
-
Germany
Novartis Investigative Site
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Heilbronn, 74072
-
Germany
Novartis Investigative Site
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Potsdam, 14467
-
Germany
Novartis Investigative Site
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Ulm, 89081
-
Germany
Greece
Novartis Investigative Site
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Larissa, 411 10
GR
Greece
Novartis Investigative Site
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Athens, 106 76
-
Greece
Novartis Investigative Site
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Athens, 18547
-
Greece
Israel
Novartis Investigative Site
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Haifa, 3525408
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Israel
Novartis Investigative Site
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Petach Tikva, 49100
-
Israel
Novartis Investigative Site
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Ramat Gan, 52621
-
Israel
Japan
Novartis Investigative Site
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Nagoya, 464 8681
Aichi
Japan
Novartis Investigative Site
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Narita, 286-8523
Chiba
Japan
Novartis Investigative Site
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Fukuoka city, 812-8582
Fukuoka
Japan
Novartis Investigative Site
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Kurume city, 830-0011
Fukuoka
Japan
Novartis Investigative Site
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Akita, 010-8543
-
Japan
Novartis Investigative Site
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Aomori, 030 8553
-
Japan
Novartis Investigative Site
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Chiba, 260 8677
-
Japan
Korea, Republic of
Novartis Investigative Site
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Seoul, 06591
Seocho Gu
Korea, Republic of
Mexico
Novartis Investigative Site
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Monterrey, 64718
Nuevo Leon
Mexico
Poland
Novartis Investigative Site
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Krakow, 30-510
Malopolskie
Poland
Novartis Investigative Site
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Gdansk, 80-952
-
Poland
Novartis Investigative Site
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Warszawa, 02 776
-
Poland
Russian Federation
Novartis Investigative Site
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Moscow, 125167
-
Russian Federation
Novartis Investigative Site
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St Petersburg, 191024
-
Russian Federation
Novartis Investigative Site
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St Petersburg, 197341
-
Russian Federation
Singapore
Novartis Investigative Site
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Singapore, 169608
-
Singapore
Spain
Novartis Investigative Site
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Sevilla, 41013
Andalucia
Spain
Novartis Investigative Site
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Santander, 39008
Cantabria
Spain
Novartis Investigative Site
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Badalona, 08916
Catalunya
Spain
Novartis Investigative Site
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Alicante, 03010
Comunidad Valenciana
Spain
Novartis Investigative Site
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La Laguna, 38320
Santa Cruz De Tenerife
Spain
Novartis Investigative Site
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Madrid, 28006
-
Spain
Novartis Investigative Site
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Madrid, 28034
-
Spain
Novartis Investigative Site
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Madrid, 28046
-
Spain
United Kingdom
Novartis Investigative Site
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Liverpool, L7 8XP
-
United Kingdom
Novartis Investigative Site
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Nottingham, NG5
-
United Kingdom

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