Study of Nilotinib as First Line Treatment in Philadelphia Chromosome Positive(Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)

NCT01274351 | Completed Phase 2 Results

• 1 other identifier: CAMN107ETR02
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 13

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).

Conditions

Chronic Myelogenous Leukemia

Keywords

First line treatment; newly diagnosed; Philadelphia chromosome positive; Chronic Myelogenous Leukemia; Ph+; CML-CP; major molecular response; Social risk

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved Major Molecular Response (MMR) During the First 12 Months

  Major Molecular Response (MMR) was defined as BCR-ABL1\^IS ≤0.1%, on the International Scale \[BCR-ABL1IS\]) by 12 months. BCR is the Breakpoint Cluster Region gene / BCR gene product and ABL is the Abelson proto-oncogene. BCR-ABL is the Fusion gene from BCR and ABL/Protein product from BCR-ABL. Participants who withdrew prematurely or those who failed to provide data for the study for other reasons were designated as premature withdrawal or inevaluable, respectively, and were included in the ITT analysis as non-responders.

  12 months

Secondary Outcomes (5)

• Percentage of Participants Who Achieved Major Molecular Response (MMR) up to 24 Months

  3, 6, 9, 15, 18, 21 and 24 months

• Percentage of Participants With Complete Cytogenetic Response (CCyR) at Month 6 and 12

  Month 6 and 12

• Percentage of Participants With Complete Hematologic Response (CHR) at Month 3, 6, 9, 12, 18 and 24

  Month 3, 6, 9, 12, 18 and 24

• Time to Major Molecular Response (MMR)

  24 months

• Duration of Major Molecular Response (MMR)

  24 months

Study Arms (1)

Nilotinib

EXPERIMENTAL

administered orally at a dose of 300 mg twice daily for 24 months

Drug: Nilotinib

Interventions

Nilotinib DRUG

administered orally at a dose of 300 mg twice daily for 24 months

Also known as: Tasigna, AMN107

Nilotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (13)

Novartis Investigative Site

Eskişehir, Meselik, 26480, Turkey (Türkiye)

Location

Novartis Investigative Site

Istanbul, TUR, 34098, Turkey (Türkiye)

Location

Novartis Investigative Site

Adana, 01330, Turkey (Türkiye)

Location

Novartis Investigative Site

Ankara, 06100, Turkey (Türkiye)

Location

Novartis Investigative Site

Bursa, 16059, Turkey (Türkiye)

Location

Novartis Investigative Site

Diyarbakır, 21000, Turkey (Türkiye)

Location

Novartis Investigative Site

Gaziantep, 27310, Turkey (Türkiye)

Location

Novartis Investigative Site

Istanbul, 34093, Turkey (Türkiye)

Location

Novartis Investigative Site

Izmir, 35040, Turkey (Türkiye)

Location

Novartis Investigative Site

Izmir, 35340, Turkey (Türkiye)

Location

Novartis Investigative Site

Okmeydanı, 34370, Turkey (Türkiye)

Location

Novartis Investigative Site

Talas / Kayseri, 38039, Turkey (Türkiye)

Location

Novartis Investigative Site

Trabzon, 61080, Turkey (Türkiye)

Location

Related Publications (2)

• 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.

  PMID: 29996726 DERIVED

• 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.

  PMID: 29486663 DERIVED

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

nilotinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2011
• First Posted: January 11, 2011
• Study Start: January 25, 2011
• Primary Completion: August 1, 2019
• Study Completion: August 1, 2019
• Last Updated: September 1, 2020
• Results First Posted: September 1, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share

Locations

TU (13)