Clinical trial NCT01274351: Study of Nilotinib as First Line Treatment in Philadelphia Chromosome Positive(Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
Official title: A Phase II Multi-center, Open-label, Non-randomized Study of Nilotinib as First Line Treatment in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Myelogenous Leukemia
Keywords: First line treatment
newly diagnosed
Philadelphia chromosome positive
Chronic Myelogenous Leukemia
Ph+
CML-CP
major molecular response
Social risk
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-01-11
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study was a local multicentric, open-label, non-randomized phase II study of nilotinib as a first line treatment in adult patients with newly-diagnosed Philadelphia chromosome-positive (Ph+) and chronic phase myeloid leukemia (CML-CP).

Detailed description: This was a multicenter, open-label, single-arm, phase 2 study of nilotinib as a frontline treatment for patients with Ph+ CMLCP. All patients received oral nilotinib 300 mg twice daily for a planned treatment duration of 24 months or until early discontinuation.

The primary efficacy end point was the cumulative rate of Major Molecular Response (MMR) in all participants by 12 months. Secondary efficacy end points included the rate of Complete Cytogenic Response (CCyR) at 6 and 12 months; cumulative rates of MMR up to 24 months; time to and durability of MMR; and cumulative rate of Complete Haematologic Response (CHR) by 12 months.

Patient evaluations, including hematologic assessments, were conducted every 15 days during the first 3 months, monthly until month 12, and then every 3 months until the end of the study (24 months). All efficacy analyses were performed in the intent-to treat population.

Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
* First cytogenetic diagnosis of CML-CP with cytogenetic confirmation of Philadelphia chromosome of (9;22) translocations within 6 months. Standard conventional cytogenetic analysis must be performed.
* Previously untreated for CML, except for hydroxyurea and/or anagrelide (except imatinib treatment for max. 31 days long)
* Adequate end organ function with following laboratory criteria: total bilirubin \< 1.5 x upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 x upper limit of normal (ULN); creatinine \< 1.5 x upper limit of normal (ULN); serum amylase and lipase ≤ 1.5 x upper limit of normal (ULN); alkaline phosphatase ≤ 2.5 x upper limit of normal (ULN) unless considered tumor related
* Serum potassium, magnesium, and phosphorus levels are equal or above the lower limit of normal prior to the first dose of study medication

Exclusion Criteria:

* Treatment with tyrosine kinase inhibitor(s) prior to study (in emergent cases where the patient requires disease management while awaiting study start, commercial supplies of imatinib at any dose may be prescribed to the patient but for no longer than 31 days in duration)
* Known cytopathologically confirmed Central Nervous System CNS infiltration
* Impaired cardiac function
* Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection)
* Acute or chronic liver, pancreatic or severe renal disease considered unrelated to disease
* Patients with another primary malignancy except if the other primary malignancy is neither currently clinically significant or requiring active intervention
* History of significant congenital or acquired bleeding disorder unrelated to cancer
* Previous radiotherapy to ≥25% of the bone marrow
* 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)
* Use of therapeutic coumarin derivatives (i.e. warfarin, acenocoumarol, phenprocoumon)
* Patients actively receiving therapy with strong Cytochrome P450 3A4 isoenzyme (CYP3A4) inhibitors (e.g, erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, mibefradil)
* Patients actively receiving therapy with medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Percentage of Participants Who Achieved Major Molecular Response (MMR) During the First 12 Months
timeFrame: 12 months
Secondary outcomes:
measure: Percentage of Participants Who Achieved Major Molecular Response (MMR) up to 24 Months
timeFrame: 3, 6, 9, 15, 18, 21 and 24 months
measure: Percentage of Participants With Complete Cytogenetic Response (CCyR) at Month 6 and 12
timeFrame: Month 6 and 12
measure: Percentage of Participants With Complete Hematologic Response (CHR) at Month 3, 6, 9, 12, 18 and 24
timeFrame: Month 3, 6, 9, 12, 18 and 24
measure: Time to Major Molecular Response (MMR)
timeFrame: 24 months
measure: Duration of Major Molecular Response (MMR)
timeFrame: 24 months
Other outcomes:
Locations:
city: Eskisehir
country: Turkey
facility: Novartis Investigative Site
state: Meselik
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
state: TUR
city: Adana
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Bursa
country: Turkey
facility: Novartis Investigative Site
city: Diyarbakir
country: Turkey
facility: Novartis Investigative Site
city: Gaziantep
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Okmeydani
country: Turkey
facility: Novartis Investigative Site
city: Talas / Kayseri
country: Turkey
facility: Novartis Investigative Site
city: Trabzon
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Saydam G, Haznedaroglu IC, Kaynar L, Yavuz AS, Ali R, Guvenc B, Akay OM, Baslar Z, Ozbek U, Sonmez M, Aydin D, Pehlivan M, Undar B, Dagdas S, Ayyildiz O, Akin G, Dag IM, Ilhan O. Frontline nilotinib treatment in Turkish patients with Philadelphia chromosome-positive chronic Myeloid Leukemia in chronic phase: updated results with 2 years of follow-up. Hematology. 2018 Dec;23(10):771-777. doi: 10.1080/10245332.2018.1498167. Epub 2018 Jul 11.
citation: Saydam G, Haznedaroglu IC, Kaynar L, Yavuz AS, Ali R, Guvenc B, Akay OM, Baslar Z, Ozbek U, Sonmez M, Aydin D, Pehlivan M, Undar B, Dagdas S, Ayyildiz O, Akkaynak DZ, Akin G, Ilhan O. Outcomes with frontline nilotinib treatment in Turkish patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. Hematology. 2018 Feb 27:1-7. doi: 10.1080/10245332.2018.1444919. Online ahead of print.