SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01744665

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

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

To evaluate molecular relapse free rates 6 months after stopping nilotinib therapy in patients who achieve MR4.5

NCT01744665 CML
MeSH: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
HPO: Chronic myelogenous leukemia

1 Interventions

Name: AMN107

Description: 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.

Type: Drug

AMN107 2 years of consolidation


Primary Outcomes

Description: 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.

Measure: Percentage of patients without molecular relapse after stopping nilotinib

Time: 6 months after stopping nilotinib therapy

Secondary Outcomes

Description: 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.

Measure: Percentage of patients without molecular relapse after stopping nilotinib

Time: 12, 18, and 36 months after stopping nilotinib

Description: 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.

Measure: Proportion of patients who regain MR4.5 after restarting nilotinib due to molecular relapse

Time: 7 years

Description: 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.

Measure: 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: 7 years

Description: 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.

Measure: Overall survival (OS) defined as the time from the date of cessation of nilotinib therapy to the date of death from any cause.

Time: 7 years

Description: Kaplan- Meier (KM) estimation method in each arm. Patients who drop out without relapse will be treated as censored observations.

Measure: 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: 7 years

Description: 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.

Measure: Change in symptom-burden scores by the MDASI-CML assessment

Time: 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

Description: 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.

Measure: Change in healthy utility assessed by EQ-5D-3L

Time: 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

Description: 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.

Measure: Change in patient quality of life assessed by SF-8

Time: 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

Purpose: Treatment

Allocation: Randomized

Single Group Assignment


There is one SNP

SNPs


1 T315I

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. --- T315I ---



HPO Nodes


HPO:
Chronic myelogenous leukemia
Genes 5
MPL BCR JAK2 KIT THPO