Safety and Efficacy of Nilotinib vs. Imatinib in the Treatment of Newly Diagnosed Chinese Ph+ CML-CP Patients

NCT01275196 | Completed Phase 3 Results

• 1 other identifier: CAMN107ECN02
• Study Type: interventional
• Target: 267
• Locations: 1 country
• Sites: 12

Brief Summary

The study will compare the efficacy and safety of Nilotinib versus Imatinib in newly diagnosed Chinese patients with CML-CP.

Conditions

Chronic Myeloid Leukemia

Keywords

Newly diagnosed,; Ph+ chronic myeloid leukemia,; CML-CP

Outcome Measures

Primary Outcomes (1)

• Major Molecular Response (MMR) at 12 Months - With Imputation.

  Major molecular response (MMR) was defined as a value of ≤ 0.1% of BCR-ABL ratio on the IS. The minimum number of control genes for a sample to be valid was 3000. For statistical comparison purpose, MMR was considered as a binary variable with patients achieving MMR grouped as 'responders' and patients not achieving MMR, patients with missing PCR evaluations or patients with atypical transcripts at baseline grouped as 'non-responders'. This endpoint was calculated based on the 12 month analysis.

  12 months

Secondary Outcomes (16)

• MMR Rate at Each Time Point

  Months 3,6,9,12,15, 18, 21, 24, 36

• Best MMR by Each Timepoint

  Months 3,6,9,12,15, 18, 21, 24, 36

• Kaplan-Meier Estimates of Time to First MMR

  End of study (up to 40 months)

• Durable MMR Rate at 24 Months

  24 months

• Kaplan-Meier Estimates of Duration of First MMR Among Patients Who Achieved MMR

  End of Study (Up to 40 months)

Study Arms (2)

Nilotinib

EXPERIMENTAL

Drug: Nilotinib

Imatinib

ACTIVE COMPARATOR

Drug: Imatinib

Interventions

Nilotinib DRUG

Nilotinib

Imatinib DRUG

Imatinib

Eligibility Criteria

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

You may qualify if:

• Patients of Chinese ethnicity greater than or equal to 18 years of age
• ECOG 0, 1, or 2.
• Patients with CML-CP (Ph+) within 6 months of diagnosis (date of initial diagnosis is the date of first cytogenetic analysis). Standard conventional cytogenetic analysis must be done on bone marrow. (FISH cannot be used)
• Diagnosis of chronic myelogenous leukemia in chronic phase with cytogenetic confirmation for the presence of Philadelphia chromosome of (9;22 translocation; less than 20 metaphases may be used for diagnosis
• Documented chronic phase CML will meet all the criteria defined by:
• \< 15% blasts in peripheral blood and bone marrow
• \< 30% blasts plus promyelocytes in peripheral blood and bone marrow
• \< 20% basophils in the peripheral blood
• ≥ 100 x 109/L (≥ 100,000/mm3) platelets
• No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
• Adequate organ function as defined by:
• Total bilirubin \< 1.5 x ULN
• SGOT and SGPT \< 2.5 x ULN
• Creatinine \< 1.5 x ULN
• Serum amylase and lipase ≤ 1.5 x ULN

You may not qualify if:

• Patients with previously documented T315I mutations;
• Treatment with tyrosine kinase inhibitor(s) prior to study entry is not allowed, except in the following situation: in emergent cases where the patient requires disease management while awaiting study start, commercial supplies of Gleevec/Glivec at any dose may be prescribed to the patient but for no longer than 2 weeks in duration.
• Treatment with IFN for more than 3 months.
• Impaired cardiac function including any one of the following:
• 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 (\<50 beats per minute)
• QTc \> 450 msec If QTcF \>450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc
• History of clinically documented myocardial infarction within past 12 months
• History of unstable angina (during the last 12 months)
• Other clinically significant heart disease (e.g., congestive heart failure or uncontrolled hypertension).
• Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required).
• Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection).
• History of significant congenital or acquired bleeding disorder unrelated to cancer.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (12)

Novartis Investigative Site

Guangzhou, Guangdong, 510080, China

Location

Novartis Investigative Site

Guangzhou, Guangdong, 510515, China

Location

Novartis Investigative Site

Wuhan, Hubei, 430022, China

Location

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

Location

Novartis Investigative Site

Tianjin, Tianjin Municipality, 300020, China

Location

Novartis Investigative Site

Hangzhou, Zhejiang, 310003, China

Location

Novartis Investigative Site

Beijing, 100044, China

Location

Novartis Investigative Site

Fuzhou, 350001, China

Location

Novartis Investigative Site

Jinan, 250012, China

Location

Novartis Investigative Site

Nanjing, 210008, China

Location

Novartis Investigative Site

Shanghai, 200025, China

Location

Novartis Investigative Site

Shanghai, 200433, China

Location

Related Publications (1)

• Wang J, Shen ZX, Saglio G, Jin J, Huang H, Hu Y, Du X, Li J, Meng F, Zhu H, Hu J, Wang J, Hou M, Hertle S, Menssen HD, Ortmann CE, Tribouley C, Yuan Y, Baccarani M, Huang X. Phase 3 study of nilotinib vs imatinib in Chinese patients with newly diagnosed chronic myeloid leukemia in chronic phase: ENESTchina. Blood. 2015 Apr 30;125(18):2771-8. doi: 10.1182/blood-2014-09-601674. Epub 2015 Mar 12.

  PMID: 25766724 DERIVED

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

nilotinib; Imatinib Mesylate

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

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

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 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2011
• First Posted: January 12, 2011
• Study Start: April 1, 2011
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: April 8, 2016
• Results First Posted: December 9, 2015

Record last verified: 2016-03

Locations

CN (12)