A Study of Imatinib and Nilotinib in Patients With Chronic Myelogenous Leukemia in Chronic Phase

An Open-label Multi-center Study of Imatinib and Nilotinib in CAMN107ECN02 On-treatment Patients With Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase After the End of CAMN107ECN02 Core Study

The extension study followed the core study CAMN107ECN02 (NCT01275196). which is an open-label, two armed study. All patients enrolled in this extension study were able to benefit from the treatment given in CAMN107ECN02 per investigator's evaluation. Therefore, in this extension study patient continued treatment of the drug (imatinib or nilotinib) which they were taking at the end of CAMN107ECN02. Treatment arms in CAMN107ECN02 were retained. As long as EC approval and agreement from investigators were obtained, the selected sites for CAMN107ECN02 were applied in this extension study.

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Drug: Imatinib; Drug: Nilotinib

Detailed Description

Up to 230 patients who benefited from the core study treatment (imatinib or nilotinib), at Investigator's discretion, were enrolled into this extension study. The patients continued receiving the open-label drugs that they were taken by the end of core study. Treatment arms in the core study were retained. No crossover between the arms was allowed.

The extension study started from the first patient last dose date in the core study and ends at the time of nilotinib was commercially available in China as a first line treatment. Eligibility evaluations were given for each patient before the enrollment. Follow-up visits at a frequency of 6 months were required to report AE, SAE and pregnancy only. No efficacy data were collected in the extension study since full efficacy had already been analyzed in the core study.

• Study Type: Interventional
• Enrollment (Actual): 225
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100044
    • Novartis Investigative Site
  • Fuzhou, China, 350001
    • Novartis Investigative Site
  • Jinan, China, 250012
    • Novartis Investigative Site
  • Shanghai, China, 200433
    • Novartis Investigative Site
  • Shanghai, China, 200025
    • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 51000
      • Novartis Investigative Site
    • Guangzhou, Guangdong, China, 510515
      • Novartis Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Novartis Investigative Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Novartis Investigative Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Novartis Investigative Site
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria

1. Patient is currently on treatment in the core study CAMN107ECN02
2. Patient who continues to derive benefit more than risk from the study treatment he/she takes in CAMN107ECN02, in the opinion of the investigator at the end of the study
3. Written informed consent must be obtained prior to enrolling in the extension study

Key Exclusion Criteria:

1. Progression to CML-AP or BC
2. Patient whose treatment assigned in CAMN107ECN02 is not appropriate any longer, per investigator's assessment.
3. History of non-compliance to medical regimens, or patients who are considered potentially unreliable and/or not cooperative.

4. Women who are (a) pregnant and(b) women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and at least 14 days after last dose of study medication. Highly effective contraception methods include:

   • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
   • 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 by follow up hormone level assessment
   • Male sterilization (at least 6 months prior to screening). For female subjects on the study the vasectomized male partner should be the sole partner for that subject.

   • Combination of any two of the following (a+b or a+c, or b+c):

     1. 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.
     2. Placement of an intrauterine device (IUD) or intrauterine system (IUS)
     3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Imatinib; Eligible patients from imatinib arm in core study CAMN107ECN02 were enrolled into imatinib arm in this study. Patients in imatinib 400 mg daily arm received imatinib daily dose of 300 mg, 400 mg or 600 mg all at once every day.	Drug: Imatinib; Imatinib 400mg QD，300mg QD or 600mg QD; Other Names: STI571, Gleevec/Glivec
Experimental: Nilotinib; Eligible patients from nilotinib arm in core study CAMN107ECN02 were enrolled into imatinib arm in this study. Patients in nilotinib arm received 300 mg BID by mouth each morning and evening approximately 12 hours apart, or 400 mg QD.	Drug: Nilotinib; Nilotinib 300mg BID or 400mg QD; Other Names: AMN107, Tasigna

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Clinically significant changes in laboratory values and vital signs were reported as AEs or SAEs, as appropriate. Only descriptive analysis.	From first dose of study treatment to 30 days after last dose of study treatment, up to 31 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2014
• Primary Completion (Actual): January 30, 2017
• Study Completion (Actual): January 30, 2017

Study Registration Dates

• First Submitted: October 21, 2014
• First Submitted That Met QC Criteria: October 21, 2014
• First Posted (Estimate): October 23, 2014

Study Record Updates

• Last Update Posted (Actual): August 19, 2019
• Last Update Submitted That Met QC Criteria: July 11, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Nilotinib; Imatinib; Chronic myelogenous leukemia; STI571; Chronic myeloid leukemia; Tasigna; AMN107; BCR-ABL Positive; Chronic myelocytic leukemia; Acute Lymphoid Leukemia; Gleevec/Glivec; Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP); Acute Lymphoblastic Leukemia (ALL) Philadelphia chromosome positive; suboptimal molecular response
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Chromosome Aberrations; Translocation, Genetic; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: CAMN107ECN02E1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com