Safety and Efficacy of CML Patients Who Switch to Nilotinib and Stop Treatment After Achieving and Sustaining MR4.5. (ENESTgoal)
This study is not yet open for participant recruitment.
Verified April 2013 by Novartis
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01744665
First received: December 5, 2012
Last updated: April 3, 2013
Last verified: April 2013
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Purpose
To evaluate molecular relapse free rates 6 months after stopping nilotinib therapy in patients who achieve MR4.5
| Condition | Intervention | Phase |
|---|---|---|
|
CML |
Drug: AMN107 |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase II Randomized, Multicenter Study of Treatment-free Remission in Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Patients Who Achieve and Sustain MR4.5 After Switching to Nilotinib |
Resource links provided by NLM:
Further study details as provided by Novartis:
Primary Outcome Measures:
- Percentage of patients without molecular relapse after stopping nilotinib [ Time Frame: 6 months after stopping nilotinib therapy ] [ Designated as safety issue: No ]Proportion of patients without confirmed loss of MR4 within 6 months following nilotinib TFR is calculated by dividing the number of patients with no documented confirmed loss of MR4, in the first 6 months after starting nilotinib TFR phase by the number of patients who entered nilotinib TFR phase.
Secondary Outcome Measures:
- Percentage of patients without molecular relapse after stopping nilotinib [ Time Frame: 12, 18, and 36 months after stopping nilotinib ] [ Designated as safety issue: No ]The proportion of patients without confirmed loss of MR4 at 12, 18, and 36 months following nilotinib TFR is calculated by dividing the number of patients with no documented confirmed loss of MR4 at 12, 18, and 36 months after starting the nilotinib TFR phase by the number of patients who entered nilotinib TFR phase.
- Proportion of patients who regain MR4.5 after restarting nilotinib due to molecular relapse [ Time Frame: 7 years ] [ Designated as safety issue: No ]The proportion of patients who regain MR4.5 after restarting nilotinib will be calculated as the number of patients who achieve MR4.5 after having lost MR4 divided by the number of patients who lost MR4.
- Progression to AP/BC and death where the "failure" event is the earliest occurrence of the following event: progression to AP/BC or death from any cause. [ Time Frame: 7 years ] [ Designated as safety issue: Yes ]The estimation of progression-free survival (PFS) following nilotinib cessation will use the Kaplan-Meier (KM) method. PFS is measured from the date of cessation of nilotinib therapy to the date of the earliest of this event: progression to AP/BC or death from any cause. Patients not known to have progressed or died on or before the cut-off date for the KM analysis will have their PFS interval right-censored at the earlier of the date of their last assessment of molecular response status and the cut off date.
- Overall survival (OS) defined as the time from the date of cessation of nilotinib therapy to the date of death from any cause. [ Time Frame: 7 years ] [ Designated as safety issue: Yes ]Kaplan-Meier (KM) estimation of OS. OS is measured from the date of start of nilotinib TFR phase to the date of death from any cause. If a patient is not known to have died, survival will be censored at the date of last contact.
- Relapse free survival is defined as time from the date of nilotinib treatment discontinuation to the first documented molecular relapse (confirmed loss of MR4.0). [ Time Frame: 7 years ] [ Designated as safety issue: Yes ]Kaplan- Meier (KM) estimation method in each arm. Patients who drop out without relapse will be treated as censored observations.
- Change in symptom-burden scores by the MDASI-CML assessment [ Time Frame: From baseline to time to when MR4.5 is confirmed and from end of Consolidation Phase to 6 and 12 months into the TFR Phase ] [ Designated as safety issue: No ]The M.D. Anderson Symptom Inventory for CML patients (MDASI-CML) is a patient reported outcomes tool which will be used to assess the nature and impact of symptom burden on life on patients. The MDASI-CML consists of 19 validated symptom items and 6 validated core interference items. Each item is assessed on an 11 point scale, 0=Not Present and 10="As Bad as You can Imagine". The symptom, interference subscale total scores and the overall total score in MDASI-CML with their change from baseline will be summarized descriptively.
- Change in healthy utility assessed by EQ-5D-3L [ Time Frame: From baseline to time to when MR4.5 is confirmed and from end of Consolidation Phase to 6 and 12 months into the TFR Phase ] [ Designated as safety issue: No ]The EQ-5D-3L questionnaire comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression and the EQ visual analog scale. Each item has 3 levels (no problems, some problems and extreme problems) and visual analog has a scale 0 to 100 (0=worst imaginable health state, 100=best imaginable health state). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized overall and by treatments arms as appropriate at baseline and all post-baseline time points. Mean and standard deviation of the visual analog scale be provided.
- Change in patient quality of life assessed by SF-8 [ Time Frame: From baseline to time to when MR4.5 is confirmed and from end of Consolidation Phase to 6 and 12 months into the TFR Phase ] [ Designated as safety issue: No ]The SF-8 questionnaire consisting of 8 items (general health, physical functioning, rolephysical, bodily pain, vitality, social functioning, role-emotional and mental health) will be used to assess the impact of nilotinib treatment discontinuation on the quality of life. Each item has a 5 or 6 point response range. Physical and mental component summary measures (calculated using a norm-based scoring method given in the instrument guidelines) and each item score will be summarized at baseline and all post-baseline time points using mean and standard deviation.
| Estimated Enrollment: | 300 |
| Study Start Date: | April 2013 |
| Estimated Study Completion Date: | August 2021 |
| Estimated Primary Completion Date: | June 2020 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: AMN107 1 year of consolidation
300 patients will be enrolled to the study. Patients who achieve MR4.5 on study will then be randomized to receive a total of either 1 or 2 years of additional nilotinib therapy. If MR4.5 is sustained during the consolidation phase, patients will be eligible to stop taking niltoinib during the treatment-free remission (TFR) phase. No head to head comparison of the 2 arms will be performed. Each arm will be compared to historical data.
|
Drug: AMN107
Nilotinib will be provided by the sponsor as the study drug. Nilotinib will be provided as 150 mg capsules. Patients will take nilotinib 300mg twice daily on study and dose modifications to 450mg once daily is permitted per protocol.
|
|
Experimental: AMN107 2 years of consolidation
300 patients will be enrolled to the study. Patients who achieve MR4.5 on study will then be randomized to receive a total of either 1 or 2 years (Consolidation Phase) of additional nilotinib therapy. If MR4.5 is sustained during the Consolidation phase, patients will be eligible to stop taking niltoinib during the treatment-free remission (TFR) phase. No head to head comparison of the 2 arms will be performed. Each arm will be compared to historical data.
|
Drug: AMN107
Nilotinib will be provided by the sponsor as the study drug. Nilotinib will be provided as 150 mg capsules. Patients will take nilotinib 300mg twice daily on study and dose modifications to 450mg once daily is permitted per protocol.
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Diagnosis of CML
- Treated with at least 1 year of imatinib
- Bcr-Abl level by PCR must be less than or equal to 0.1% and greater than 0.0032% by PCR reported on the International scale. This will be confirmed during screening
- Written informed consent obtained prior to any screening procedures performed
Exclusion Criteria:
- T315I mutation
- Prior imatinib failure or had accelerated phase or blast crisis CML
- Impaired cardiac function (defined futher in the protocol)
- Pregnant or lactating women
Other protocol-defined inclusion/exclusion criteria may apply.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01744665
Contacts
| Contact: Novartis Pharmaceuticals | 1-888-669-6682 | |
| Contact: Novartis Pharmaceuticals |
Locations
| United States, California | |
| City of Hope National Medical Center Dept of Oncology | Not yet recruiting |
| Duarte, California, United States, 91010-3000 | |
| Contact +1 626 256 4673 ext 60134 | |
| Principal Investigator: David S Snyder | |
| United States, Georgia | |
| Georgia Cancer Specialists Georgia Cancer | Not yet recruiting |
| Decatur, Georgia, United States, 30033 | |
| Contact 770-496-9427 | |
| Principal Investigator: Mansoor Saleh | |
| United States, Illinois | |
| Stroger Cook County Hospital Division of Hematology & Onc | Not yet recruiting |
| Chicago, Illinois, United States, 60612 | |
| Contact 312-864-7257 | |
| Principal Investigator: Rosalind Catchatourian | |
| United States, Indiana | |
| Indiana Blood and Marrow Institute St. Francis Health | Not yet recruiting |
| Beach Grove, Indiana, United States, 46107 | |
| Contact 317-865-5500 | |
| Principal Investigator: Luke P. Akard | |
| United States, Kansas | |
| Cancer Center of Kansas | Not yet recruiting |
| Witchita, Kansas, United States, 67214-3728 | |
| Contact 316-262-4467 | |
| Principal Investigator: Shaker R. Dakhil | |
| United States, Maryland | |
| St. Agnes Hospital | Not yet recruiting |
| Baltimore, Maryland, United States, 21229 | |
| Contact 410-368-3412 | |
| Principal Investigator: Carole Miller | |
| United States, Massachusetts | |
| Dana Farber Cancer Institute D F C I | Not yet recruiting |
| Boston, Massachusetts, United States, 02115 | |
| Contact 617-632-6685 | |
| Principal Investigator: Martha Wadleigh | |
| United States, Utah | |
| University of Utah / Huntsman Cancer Institute Huntsman Cancer Center | Not yet recruiting |
| Salt Lake City, Utah, United States, 84103 | |
| Contact 801-581-6363 | |
| Principal Investigator: Michael W. Deininger | |
| United States, Wisconsin | |
| Medical College of Wisconsin Med College of WI | Not yet recruiting |
| Milwaukee, Wisconsin, United States, 53226 | |
| Contact 414-805-4600 | |
| Principal Investigator: Ehab Atallah | |
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
More Information
No publications provided
| Responsible Party: | Novartis ( Novartis Pharmaceuticals ) |
| ClinicalTrials.gov Identifier: | NCT01744665 History of Changes |
| Other Study ID Numbers: | CAMN107AUS37 |
| Study First Received: | December 5, 2012 |
| Last Updated: | April 3, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Novartis:
|
CML, chronic myeloid leukemia, stop, niotinib, discontinue, imatinib, switch, MR4.5, undetectable, bcr-abl |
Additional relevant MeSH terms:
|
Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia Neoplasms by Histologic Type |
Neoplasms Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases |
ClinicalTrials.gov processed this record on May 16, 2013