Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Leukemia, Myeloid, Chronic-Phase

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

All Drugs and Chemicals

Amino Acids

Nilotinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Jorge Cortes, MD

The goal of this clinical research study is to learn if an experimental agent, AMN107 (nilotinib), can help to control CML in chronic phase. The safety of this experimental agent will also be studied.

Nilotinib is a drug that is designed to block a protein that is responsible for the development of CML.

If you are found to be eligible to take part in this study, you will take 2-4 nilotinib capsules or tablets by mouth 2 times a day (4-8 capsules or tablets a day total) every day, at least 8 hours apart. Nilotinib should be taken each morning and evening with a large glass of water. The study medication will be given to you every 3 - 12 months. You will also be given a "pill diary" to write down when (day and time) you take the drug. You will also write in the diary any side effects you may experience. You should bring the diary, any unused capsules or tablets, and empty containers of nilotinib with you to every visit to the study doctor. Any unused supplies must be returned at the end of the study.

Every 1-4 weeks during the first 4 weeks of the study, you will have around 2 teaspoons of blood drawn for routine blood tests. The blood tests will then be repeated every 4-8 weeks (or more often if your doctor feels it is necessary) until you have been on study for 6 months, then every 3 to 6 months for another 18 months. After that, you may have the blood tests repeated as often as the doctor thinks it is needed. A bone marrow sample will also be taken every 3-4 months for the first year and then every 6-12 months in the 2nd year, then every 2-3 years for as long as you are on the study to check on the status of the disease. Additionally, blood (about ½ tablespoon) will be drawn or a bone marrow sample will be collected every 3-4 months for the first year and then every 6-12 months until 2 years, and then about one time a year for as long as you are on the study to check on the status of the disease. However, if you are in complete remission after Year 2, your doctor will decide when you will have a bone marrow aspiration. But you will still have blood drawn (about ½ tablespoon) every 1 - 3 years to check the status of your disease. An ECG will be repeated around Day 5, and then at about 6 weeks and about 3 months.

You will be asked to visit the doctor for a physical exam and to have vital signs measured periodically. These visits will be scheduled at least every 3 to 4 months the first year. After the first year, the study staff will recommend that you have physical exams once every year. The visits may be scheduled more often depending on the status of the disease.

Treatment may be continued for up to 8-10 years or as long as the doctor feels it is necessary to control the leukemia. If the disease gets worse or you experience any intolerable side effects, you will be taken off the study and your doctor will discuss other treatment options with you.

This is an investigational study. Nilotinib is FDA approved. A total of 150 patients will take part in this study. All will be enrolled at MD Anderson.

Phase II Nilotinib With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (CML)

Therapy of Early Chronic Phase Chronic Myelogenous Leukemia (CML) With Oral Nilotinib

Polymerase chain reaction (PCR) Ratio BCR-Abl/Abl of 0% after 12 months of therapy with Nilotinib by international standard.

Complete hematologic remission classified according to suppression of Philadelphia chromosome (Ph) by cytogenetics or i Fluorescence in situ hybridization (FISH)

1. No cytogenetic response - Ph positive 100%
2. Minor cytogenetic response - Ph positive 35-90%
3. Partial cytogenetic response - Ph positive 1-34%
4. Complete cytogenetic response - Ph positive 0% Major cytogenetic response = complete + partial (Ph positive \<35%)

Novartis

M.D. Anderson Cancer Center

400 mg orally twice daily

Nilotinib: 400 mg orally twice daily

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Cortes,Jorge E, MD./Professor

Participants With Complete Molecular Response (Molecular CR)

Number of Participants With Complete Cytogenetic Response (CCyR)

Overall Study

Digestive System Diseases

Skin and Connective Tissue Diseases

Gastrointestinal Stromal Tumors

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Antineoplastic Agents

Imatinib Mesylate

AMN107, STI571

Novartis Pharmaceuticals

This study is an open-label, multicenter, Phase I dose-escalation study of the combination of AMN107 and imatinib (STI571) in patients with imatinib-resistant GIST. This study is designed to determine the Phase II dose of AMN107 and imatinib when administered together in patients with imatinib-resistant GIST, and to characterize the safety, tolerability and pharmacokinetic (PK) profile of this combination.

Study of AMN107 With Imatinib in Gastrointestinal Stromal Tumors (GIST)

A Phase I Multicenter, Dose Escalation Study of AMN107 in Combination With Imatinib on a Continuous Daily Dosing Schedule in Adult Patients With Imatinib-resistant Gastrointestinal Stromal Tumors (GIST)

MTD is defined to be the highest dose of AMN in combination with imatinib given for at least 21 days in the first treatment cycle

400 mg by mouth twice a day for 7 days. Patients on Arm 2 will continue to receive Nilotinib until they have disease progression or are resectable.

Jonathan Trent, MD, PHD, BS

The goal of this clinical research study is to learn if Tasigna® (nilotinib) can cause tumor cells to shrink and/or die in patients with GIST who are scheduled for surgery or may be eligible for surgery. The safety of this drug will be studied. Researchers also want to use imaging scans to study the changes in tumor size that may be caused by using nilotinib.

GIST is a rare cancer known as a soft-tissue sarcoma that forms in the gastrointestinal (GI) tract and may spread to other parts of the body. However, sometimes GIST stays in the GI tract where it may possibly be removed by surgery. While some chemotherapy drugs, such as imatinib mesylate, are effective in shrinking or controlling GIST, some types of GIST tumors do not respond to imatinib. Researchers want to find out if nilotinib (a drug similar to imatinib) causes GIST cells to die, so that the tumors shrink enough to be removed by surgery.

The Study Drugs:

Nilotinib is designed to prevent cells from multiplying by causing tumor cells to shrink and/or die. This may prevent the cancer from growing.

Study Arms and Study Drug Administration:

If you are found to be eligible to take part in this study, a surgeon from M. D. Anderson will check your imaging scans to decide if the tumor can be surgically removed.

Participants in this research study will be assigned to either Arm 1 or Arm 2, based on whether the tumor is able to be removed by surgery at this point.

Arm 1:

If the surgeon thinks the tumor is able to be removed during surgery, you will be assigned to Arm 1. You will receive nilotinib pills by mouth 2 times a day for 7 days. You will receive a pill diary and will be shown how to record the date and time for each dose received.

After the week of nilotinib therapy, you will be scheduled to have the GIST removed during surgery. Tumor tissue that is removed during surgery will be used for research testing. Some of these tests will help researchers learn how effectively nilotinib kills tumor cells. Your DNA and RNA (the genetic material in your cells) will also be collected from these tissue samples and used to help researchers understand how these tumor cells survive, divide, and die as a result of nilotinib.

After 4-6 weeks of recovery time after surgery, you will receive standard of care treatment off-study.

An assigned research nurse will see you at each clinic visit and will serve as the first contact for any questions or concerns. During the course of this study, you will be asked to report any serious problems or concerns at each study visit. If you have concerns or questions between each study visits, you may contact your study nurse through the Sarcoma Center at M. D. Anderson.

Arm 1 Study Visits:

Participants in Arm 1 will have the following tests and procedures performed:

On Day -7, you will begin taking nilotinib.

On Day -1:

* You will have a dynamic CT scan within 36 hours before surgery to check the status of the disease.
* Blood (about 2-3 teaspoons) will be drawn for routine tests.
* You will have an ECG.

On Day 0, you will have surgery to remove the GIST.

On Day 56:

* You will be asked about your health, any drugs you may be taking, and any side effects you may have experienced.
* You will have a physical exam, including measurement of vital signs and weight.
* Your performance status will be recorded.
* You will have a chest x-ray.
* You will have a standard CT scan or an MRI scan to check the status of the disease.
* Blood (about 2-3 teaspoons) will be drawn for routine tests.

Every 3 months:

* You will be asked about your health, any drugs you may be taking, and any side effects you may have experienced.
* You will have a physical exam, including measurement of vital signs and weight.
* Your performance status will be recorded.
* You will have a standard CT scan or an MRI scan to check the status of the disease.
* Blood (about 2-3 teaspoons) will be drawn for routine tests.

Arm 2:

If the surgeon thinks the tumor is not able to be surgically removed at this time, or that the tumor needs to shrink before it can be removed during surgery, you will be assigned to Arm 2. You will receive nilotinib pills by mouth 2 times a day for 7 days. You will receive a pill diary and will be shown how to record the date and time for each dose received.

After the week of nilotinib therapy, you will be scheduled to have a biopsy on what is counted as Day 0 on your pill diary. After 7 days of recovery from the biopsy, you will continue receiving nilotinib on the same schedule (2 times a day by mouth).

After 8 weeks of nilotinib therapy, you will have more scans performed to measure the size of the tumor. These scans will include a CT scan of your abdomen or pelvis. You may have a magnetic resonance imaging (MRI) scan instead, if you have chronic kidney disease.

If the scans show that the tumor has gotten smaller, you will meet with the surgeon to discuss surgery to remove the tumor. If you are scheduled to have surgery, you will stop taking nilotinib 1 day before your surgery date. If the tumor has gotten bigger, you will be taken off study treatment, and other treatment options will be discussed with you. If the scan shows that the tumor is unchanged, you will continue to receive nilotinib until the tumor either shrinks (and you are able to have surgery) or gets bigger (and you are taken off study treatment).

Tumor tissue that is removed during your scheduled biopsy or during surgery will also be used for biological and genetic testing.

After you have surgery, you will receive standard of care treatment off-study, depending on the results of the surgery.

Your doctor may recommend that you begin taking imatinib mesylate after surgery (or if the disease has gotten worse and you are not able to have surgery). In many cases, imatinib mesylate is given on a daily basis for 1-2 years to lower the risk of the disease coming back. During the time after the surgery, information will be collected about your overall health.

If the disease gets worse while you are on study, and you agree, you will be asked to have a tumor biopsy of an easily accessible area. If this happens, this procedure will be described to you in more detail, and you will sign a separate consent.

An assigned research nurse will see you at each clinic visit and will serve as the first contact for any questions or concerns. During the course of this study, you will be asked to report any serious problems or concerns at each study visit. If you have concerns or questions between each study visits, you may contact your study nurse through the Sarcoma Center at M.D. Anderson.

Arm 2 Study Visits:

Participants in Arm 2 will have the following tests and procedures performed:

On Day -7, you will begin taking nilotinib.

On Day -1:

* You will have a a dynamic CT scan within 36 hours before your biopsy to check the status of the disease.
* Blood (about 2-3 teaspoons) will be drawn for routine tests.
* You will have an ECG.

On Day 0:

-You will have a tumor tissue biopsy performed. To collect a tumor tissue biopsy, the skin above and around the tumor area is numbed with anesthetic, and a sample of tumor tissue is withdrawn through a large needle.

On Day 56:

* You will be asked about your health, any drugs you may be taking, and any side effects you may have experienced.
* You will have a physical exam, including measurement of vital signs and weight.
* Your performance status will be recorded.
* You will have a chest x-ray.
* You will have a standard CT scan or an MRI scan to check the status of the disease.
* Blood (about 2-3 teaspoons) will be drawn for routine tests.

Depending on the results of the tests at Day 56 you will either have surgery, continue nilotinib, or be taken off study and switched to another therapy.

Every 3 months:

* You will be asked about your health, any drugs you may be taking, and any side effects you may have experienced.
* You will have a physical exam, including measurement of vital signs and weight.
* Your performance status will be measured.
* You will have a standard CT scan or an MRI scan to check the status of the disease.
* Blood (about 2-3 teaspoons) will be drawn for routine tests.

Additional Testing for Both Groups:

You will have blood (about 1 teaspoon each time) drawn for pharmacokinetic (PK) testing. PK testing measures the amount of study drug in the body at different time points. These PK samples will be drawn after the first 6 days of nilotinib (Day -1) and either at the end-of-treatment visit or at any point that the disease gets worse.

When/if your treatment is interrupted for any reason and/or your dose is changed in any way, you will also have ECGs performed. You will have an additional ECG 7 days after this.

End-of-Treatment Visit:

At this visit, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your vital signs and weight.
* You performance status will be recorded.
* You will be asked about your health, any drugs you may be taking, and any side effects you may have experienced.
* Blood (about 1 tablespoon) will be drawn for routine tests.
* You will have an ECG.
* You will have a CT or MRI scan to check the status of the disease.

Length of Study:

You may continue taking the study drug for 1 week (Arm 1) before you have surgery. You may continue taking the study drug for as long as your doctor thinks it is in your best interest, or until you are able to have surgery (Arm 2). You will no longer be able to take the study drug if the disease gets worse or intolerable side effects occur.

Follow-up Testing:

You will be asked to return to the clinic every 3 months for standard follow-up testing, including routine blood tests and CT scans.

This is an investigational study. Nilotinib is FDA approved and commercially available for the treatment of certain types of chronic myeloid leukemia. Its use in patients with GIST is investigational.

Up to 24 patients will take part in this study. All will be enrolled at M. D. Anderson.

Tasigna Neoadjuvant Gastrointestinal Stromal Tumor (GIST)

A Two-Arm Study of Preoperative Nilotinib for Patients With Resectable or Potentially Resectable Gastrointestinal Stromal Tumor (GIST)

Changes assessed by tumor cell apoptosis measured by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.

Gastrointestinal Agents

Lactitol

Patients with minimum 3 years of tyrosine kinase inhibitor treatment (first with imatinib and then switched to nilotinib) since initial diagnosis, at least 2 years of nilotinib treatment prior to study entry and who achieved MR4.5 (local laboratory assessment) during nilotinib treatment, and determined by a Novartis designated central PCR lab assessment at screening

Nilotinib was dosed by weight or body surface area.

Nilotinib 300 mg BID or 400 mg BID was be administered orally at approximately 12 hour intervals, and must not have been taken with food. The capsules were to be swallowed whole with water.

No food should have been consumed for at least 2 hours before the dose was taken and no additional food should have been consumed for at least one hour after the dose was taken. Patients were also allowed to enter this study on the same dose they were taking prior to study entry. Patients who required permanent dose reduction from their original starting dose were to be allowed to enter this study on the same dose only if the patient maintained this dose for a minimum of 6 months prior to study entry.

nilotinib

A clinical research study to find out if it is safe to stop the drug nilotinib (Tasigna) in chronic myeloid leukemia (CML) patients. Patients who started treatment with imatinib (Gleevec) when they were first diagnosed with CML, then switched to nilotinib (Tasigna) for at least 2 years with the combined time on imatinib (Gleevec) and nilotinib (Tasigna) for at least 3 years and have very small amount of leukemia cells remaining after the nilotinib (Tasigna) treatment will qualify for the study.

The Primary objective was to evaluate the proportion of patients in TFR within 48 weeks following nilotinib cessation.

This study originally consisted of seven phases (five treatment phases and two treatment-free phases) from which two were the focus of this primary analysis report (consolidation, TFR and treatment re-initiation) The study consisted of 2 main phases: Consolidation and TFR

Nilotinib treatment consolidation phase (NTCS): Patients who satisfied all inclusion/exclusion criteria were enrolled in the consolidation phase and continued to receive nilotinib for 52 weeks at the dose which the patient was receiving prior to study entry. If a patient maintained MR4.5 throughout the consolidation phase, he/she was eligible to enter in the TFR phase. If a patient had confirmed loss of MR4.5 during the consolidation phase, he/she was not eligible to enter in the TFR phase and continued nilotinib treatment.

Nilotinib TFR phase: Patients who were eligible to enter in the TFR phase after completing the 52 week consolidation phase stopped taking nilotinib on the first day of the TFR phase. Duration of this phase was up to 520 weeks after the last patient enters in the TFR phase.

Nilotinib treatment re-initiation phase (NTRI): If a patient had a confirmed loss of MR4 (two consecutive BCR-ABL \>0.01% IS) or loss of MMR (BCR-ABL \>0.1% IS) in the TFR phase, the patient restarted nilotinib treatment. Patients will be on nilotinib treatment for up to 520 weeks after the last patient entered the nilotinib TFR phase, or until a patient experience unacceptable toxicity, disease progression and/or treatment discontinued at the discretion of the Investigator or if the patient withdrew consent. Nilotinib cessation was not attempted for a second time in the patient who reinitiated treatment or discontinued following the TFR phase.

Nilotinib treatment continuation phase (NTCT) and Nilotinib treatment prolonged continuation phase (NTCT-P): Patients who were not eligible to enter into the TFR phase after completing the 52-week NTCS phase entered the nilotinib treatment continuation (NTCT) phase and would continue treatment with nilotinib for another 52 weeks (a total of 104 weeks of treatment). Patients who were not able to maintain MR4.5 and had a confirmed loss of MR4.5 during the NTCT phase were not eligible to enter the TFR-2 phase. These patients entered into the nilotinib prolonged treatment continuation phase (NTCT-P) and continued nilotinib treatment until 520 weeks after the last patient entered the nilotinib TFR phase, or until the patients experience unacceptable toxicity, disease progression and/or treatment would be discontinued at the discretion of the Investigator or withdrawal of consent.

Nilotinib TFR-2 phase: Patients who maintained MR4.5 during the NTCT phase were eligible to cease nilotinib treatment and enter the TFR-2 phase. The duration of the nilotinib TFR-2 phase is up to 520 weeks after the last patient entered the TFR phase. Patients stopped taking nilotinib therapy on the day they entered the TFR-2 phase.

Nilotinib treatment re-initiation-2 (NTRI-2): If a patient had a loss of MMR or a confirmed loss of MR4 during the TFR-2 phase, he/she entered the nilotinib treatment re-initiation-2 (NTRI-2) phase and resumed nilotinib treatment at a dose of either 300 mg or 400 mg bid.

Safety follow-up was performed within 30 days after the last dose of study treatment or the last day in TFR/TFR-2.

Post-treatment follow-up visits were performed every 12 weeks up to 520 weeks after the last patient entered the nilotinib TFR phase.

Treatment-free Remission After Achieving Sustained MR4.5 on Nilotinib (ENESTop)

A Phase II, Single Arm, Open Label Study of Treatment-free Remission in Chronic Myeloid Leukemia (CML) Chronic Phase (CP) Patients After Achieving Sustained MR4.5 on Nilotinib

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

TFR is defined as no confirmed loss of MR4 (Molecular response 4.0 log reduction from baseline) or loss of MMR (major molecular response) and no re-starting of nilotinib therapy within 12 months following cessation of nilotinib. Confirmed loss of MR4 is two consecutive BCR-ABL \> 0.01% IS. Loss of MMR does not require confirmation. Percentage of patients in TFR is calculated by dividing the number of patients with no documented confirmed loss of MR4, no documented loss of MMR and no re-starting of nilotinib therapy in the first 48 weeks after starting nilotinib TFR phase by the number of patients who entered nilotinib TFR phase, and multiplied by 100.

TFR is defined as no confirmed loss of MR4 (molecular response 4.0 log reduction from baseline) or loss of MMR (major molecular response) and no re-starting of nilotinib therapy within 12 months following cessation of nilotinib. Confirmed loss of MR4 is two consecutive BCR-ABL \> 0.01% IS. Loss of MMR does not require confirmation. Percentage of patients in TFR is calculated by dividing the number of patients with no documented confirmed loss of MR4, no documented loss of MMR and no re-starting of nilotinib therapy in the first 96, 144, 192, 264 weeks and within 6,7,8,9 and 10 years after starting nilotinib TFR phase by the number of patients who entered nilotinib TFR phase, multiplied by 100.

Kaplan-Meier (KM) estimation of PFS. PFS is measured from the date of start of nilotinib TFR phase (cessation of nilotinib) to the date of the earliest of the event: progression to AP/BC, or death from any cause. Patients not known to have recurred 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 (cytogenetic, hematology or extramedullary) for patients who are still on study and at the date of last contact for patients are in follow-up.

Kaplan-Meier (KM) estimation of TFS is measured from the date of the start of the nilotinib TFR phase to the date of the earliest of the following: loss of MMR, confirmed loss of MR4, re-start of nilotinib treatment, progression to AP/BC or death from any cause. Patients not known to have had any of the events or died on or before the cut-off date for the KM analysis will have their TFS interval right-censored at the earlier of the date of their last assessment (PCR, cytogenetic, hematology or extramedullary) for patients who are still on study and at the date of last contact for patients are in follow-up. A TFS sensitivity analysis will be conducted by considering discontinuation from TFR phase due to any reason as an event, in addition to the events as defined above

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.

Descriptive statistics of BCR-ABL over time after re-start of nilotinib therapy. ABL= Abelson leukemia virus and BCR=Break point cluster region

Percentage of patients who are in stable MMR (stable MMR=BCR-ABL ≤ 0.1% IS) at 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks after achievement of that response in the nilotinib re-initiation phase for 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks is calculated by dividing the number of patients achieving MMR any time during the nilotinib re-initiation phase and having the same response at 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks after the first achievement of MMR, irrespective of whether there is loss of MMR in between, by the number of patients who achieved MMR at any time during the nilotinib re-initiation phase, and multiplied by 100.

Percentage of patients who are in stable MR4 (stable MR4=BCR-ABL ≤ 0.01% IS) at 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks after achievement of that response in the nilotinib re-initiation phase for 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks is calculated by dividing the number of patients achieving MR4 any time during the nilotinib re-initiation phase and having the same response at 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks after the first achievement of MR4, irrespective of whether there is loss of MR4 in between, by the number of patients who achieved MR4 at any time during the nilotinib re-initiation phase, and multiplied by 100.

Percentage of patients who are in stable MR4.5 (stable MR4.5=BCR-ABL ≤ 0.0032% IS) at 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks after achievement of that response in the nilotinib re-initiation phase for 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks is calculated by dividing the number of patients achieving MR4.5 any time during the nilotinib re-initiation phase and having the same response at 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks after the first achievement of MR4.5, irrespective of whether there is loss of MR4.5 in between, by the number of patients who achieved MR4.5 at any time during the nilotinib re-initiation phase, multiplied by 100.

Any sign or symptom that occurs during the study treatment plus 30 days post treatment.

NTCS Phase

TFR Phase

NTRI Phase

NTCT Phase

TFR-2 Phase

NTRI-2 Phase

nilotinib treatment prolonged continuation

NTCT-P Phase

All Patients

Caucasian

Black

Asian

Native American

Other

Race/Ethnicity, Customized

Safety Set: The safety set included all patients who received at least one dose of study medication in the Consolidation Phase.

Study Director

Full Analysis Set (FAS): FAS included all patients who entered the TFR phase.

Percentage of Patients in Treatment Free Remission (TFR) Within 48 Weeks

Percentage of Patients in Treatment Free Remission (TFR) Within 96, 144, 192, 264 Weeks and Within 6,7,8,9 and 10 Years

Progression Free Survival (PFS) to Accelerated Phase/Blast Crisis (AP/BC) or Death

Treatment Free Survival (TFS)

Overall Survival (OS)

Change in BCR-ABL (Oncoprotein Product of BCR-ABL Fusion Gene) Transcripts After Re-start of Nilotinib Therapy

Percentage of Patients With Stable MMR in Nilotinib Re-initiation Phase

Percentage of Patients With Stable MR4 in Nilotinib Re-initiation Phase

Percentage of Patients With Stable MR4.5 in Nilotinib Re-initiation Phase

Philadelphia Chromosome

Participants received two 150 \[a total of 300 mg at each dosing\] mg nilotinib capsules twice daily (bid) orally every morning and every evening approximately 12 hours apart and two 200 mg capsules \[a total of 400 mg at each dosing\] for patients enrolled prior to Protocol Amendment 1).

The purpose of this exploratory study will be to examine changes in chronic low grade chronic adverse events, measured by Common Terminology Criteria for Adverse Events (CTCAE) grading, when patients are switched from imatinib to nilotinib therapy.

An Exploratory Trial to Assess the Improvement of Adverse Events in Chronic Myelogenous Leukemia Patients Treated With Imatinib When Switched to Nilotinib Treatment

An Exploratory Trial to Assess the Improvement of Chronic Low-grade Non-hematologic Adverse Events Experienced by Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Treated With Imatinib When Switched to Nilotinib Treatment

A patient was considered improved if 50% or more of the chronic imatinib-related chronic low grade nonhematologic AEs showed improvement (a decrease in CTCAE \[Common Terminology Criteria for Adverse Events\] grade or complete resolution).

Time to complete cytogenetic response is defined as time from baseline to first time of CCyR as documented by bone marrow cytogenetics. Cytogenetic response was assessed as applicable by bone marrow cytogenetics 6, 12, and 18 months after starting imatinib therapy. Assess CCyR by bone marrow cytogenics

Major Molecular Response (MMR) value at Molecular MD is designated a percentage, which is equivalent to a 3-log reduction from a standardized baseline value from the International Randomized Interferon versus STI571 (IRIS) study or 0.1% per International Scale (IS). Time to MMR is defined as time from baseline to first time of MMR as documented by RQ-PCR

Levels of BCR-ABL transcripts were determined by quantitative RQ-PCR testing of peripheral blood and analyzed at a central testing laboratory. Log reduction in BCR-ABL transcripts levels from the standardized baseline value will be calculated for each sample from the reported percent ratio of BCR-ABL transcripts versus control gene transcripts converted to a reference standard.

Duration of Complete Cytogenetic Response is defined as the time from first CCyR to first loss of CCyR as documented by bone marrow cytogenetics, or by FISH assay, whichever is earlier. The duration of CCyR begins on the day of enrollment for patients reporting CCyR at baseline.

For time to CCyR, an event is defined as achievement of CCyR documented by bone marrow cytogenetics.

Duration of Major Molecular Response is defined as the time from first MMR to first loss of MMR as documented by RQ-PCR. The duration of MMR begins on the day of enrollment for patients reporting MMR at baseline.

For time to MMR, an event is defined as achievement of MMR documented by RQ-PCR. Patients with MMR at the Screening RQ-PCR assay are counted as having time to MMR equal to 0.

Time to optimal improvement is defined as the time when the sum of the total CTCAE toxicity grades for a patient's chronic low-grade imatinib-related adverse events reaches its minimum value.

The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.

Safety Set : All participants who received at least one dose of study drug and had at least one post-baseline safety assessment.

End of Cycle 1

End of Cycle 2

End of Cycle 3

Full Analysis Set (FAS): All participants who received at least one dose of study drug.

Percentage of Participants With Improvement in Imatinib Related Chronic Low Grade Non Hematologic Adverse Event (AE) After Switch to Treatment With Nilotinib at End of Cycle 3

Cycle 1

Cycle 2

Cycle 3

Cycle 6

Cycle 9

Cycle 12

FAS : All participants who received at least one dose of study drug.

Percentage of Participants Achieving Complete Cytogenetic Response (CCyR) After Switching to Nilotinib for Participants Not Reporting CCyR at Baseline

Percentage of Participants Achieving Major Molecular Response (MMR) After the Switch in the Therapy for Participants Not Reporting MMR at Baseline

FAS: All participants who received at least one dose of study drug.

Log Change in BCR-Abl Transcript Level From Baseline After the Switch Therapy

Participants with CCyR at baseline

Participants achieving CCyR on study

Duration of Complete Cytogenetic Response

Time to Complete Cytogenetic Response in Participants Not Reporting at Baseline

Participants with MMR at baseline

Participants achieving MMR on study

Duration of Major Molecular Response

Time to Major Molecular Response (MMR) in Participants With MMR Absent at Baseline

Time to Optimal Imatinib-related Adverse Event Improvement

Sunitinib

AMN107

This study will evaluate the efficacy and safety of nilotinib in gastrointestinal stromal tumors patients who failed imatinib and sunitinib therapy.

Efficacy and Safety of AMN107 in Patients With GastroIntestinal Stromal Tumors (GIST) Who Have Failed Both Imatinib and Sunitinib

A Multi-center Phase II Study to Evaluate the Efficacy and Safety of AMN107 (Nilotinib) in Patients With Gastrointestinal Stromal Tumors Who Have Progressed on or Are Intolerant to Both Imatinib and Sunitinib

Nilotinib oral dose of 400 mg BID (800 mg/day) continuous dosing for up to 24 months. Nilotinib oral dose of 300 mg BID (600 mg/day) continuous dosing in case of intolerance. Nilotinib oral dose of 400 mg QD (400 mg/day) continuous dosing in case of intolerance

Novartis Biociências SA - Brazil

This is an open label, non randomized, prospective, multicenter, phase II clinical trial evaluating nilotinib 400 mg BID for the treatment of newly diagnosed CML-AP patients.

Patients enrolled into the study will receive 400mg of nilotinib, orally, twice daily (800mg/day)

Patients will be evaluated for safety throughout the study and for response every month for the first 3 months, then every 3 months thereafter up to month 24.

BCR-ABL transcripts measurement by QRT-PCR and mutation analyses will be done on peripheral blood samples and cytogenetic analyses on bone marrow aspirates.

Laboratory tests (hematology, blood chemistry), ECG and physical examination will be done on every visit.

Drug pharmacokinetics will be assessed in this study. For the screening Baseline periods, see chart attached

Trial Evaluating Nilotinib as Treatment for Newly Diagnosed CML Patients in Accelerated Phase.

A Phase II, Non Randomized, Open Label, Trial Evaluating Nilotinib as Treatment for Newly Diagnosed CML Patients in Accelerated Phase.

The toxicity criteria will be evaluated according to National Cancer Institute - Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 3.0.

To test the efficacy of nilotinib 400 mg BID in inducing complete cytogenetic response (CCyR) at 12 months in newly diagnosed CML-AP patients

Evaluate the rate of complete hematologic response (CHR) with nilotinib 400 mg BID at 3 months.

Evaluate the Quality of Life by FACT-Leu Version 4 questionnaire at 3, 6, 9, 12, 15, 18 and 24 months.

Evaluate the median time to achieve molecular response and the cumulative probability of obtaining molecular response during the first 2 years of treatment. This will be undertaken through the analysis of the best molecular response at 3, 6, 12, 18 and 24 months. MMR will be preferred and it will be defined as a BCR-ABL/ABL ratio ≤ 0.1% IS using RQ-PCR, but any log reduction between 1 and 4,5 logs will be considered a molecular response.

Evaluate the proportion of patients achieving CCyR at 3, 6, 12, 18 and 24 months or undetectable BCR-ABL levels at 12, 18 and 24 months as well as the duration of sustained response.

To correlate the probability of reaching MMR, CMR and CCyR with the risk of progression to blastic phase, relapse and overall survival.

This open-label, multicenter trial will evaluate the efficacy and safety of treatment with AMN107 in chronic myelogenous leukemia (CML) patients that are resistant and/or intolerant to imatinib mesylate therapy.

Efficacy and Safety of Oral AMN107 in Adults With Chronic Myelogenous Leukemia Resistant and/or Intolerant to Imatinib Mesylate Therapy

Nilotinib (AMN107)

imatinib (STI571)

This study will evaluate efficacy and safety of nilotinib versus imatinib in adult patients with unresectable or metastatic gastrointestinal stromal tumors (GIST).

A Study of Nilotinib Versus Imatinib in GIST Patients

A Randomized, Open Label, Multi-center Phase III Study to Evaluate the Efficacy and Safety of Nilotinib Versus Imatinib in Adult Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors (GIST)

PFS was defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Imatinib

Crossover Nilotinib

Crossover Imatinib

patients were on imatinib 400mg once daily in the core phase and then crossed over to nilotinib 400 mg twice a day in the extension phase

Imatinib First, Then Nilotinib

patients were on nilotinib 400 mg twice a day in the core phase and then crossed over to in the extension phase imatinib 400mg once daily

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase II Nilotinib With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (CML)	NCT00129740	Leukemia, Myelo...	Nilotinib	16 Years -	M.D. Anderson Cancer Center
Study of AMN107 With Imatinib in Gastrointestinal Stromal Tumors (GIST)	NCT00135005	Gastrointestina...	AMN107, STI571	18 Years -	Novartis
Phase II Nilotinib With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (CML)	NCT00129740	Leukemia, Myelo...	Nilotinib	16 Years -	M.D. Anderson Cancer Center
Tasigna Neoadjuvant Gastrointestinal Stromal Tumor (GIST)	NCT01270893	Gastrointestina...	Nilotinib	18 Years -	M.D. Anderson Cancer Center
Phase II Nilotinib With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (CML)	NCT00129740	Leukemia, Myelo...	Nilotinib	16 Years -	M.D. Anderson Cancer Center
Treatment-free Remission After Achieving Sustained MR4.5 on Nilotinib (ENESTop)	NCT01698905	Chronic Myeloid...	nilotinib	18 Years -	Novartis
An Exploratory Trial to Assess the Improvement of Adverse Events in Chronic Myelogenous Leukemia Patients Treated With Imatinib When Switched to Nilotinib Treatment	NCT00980018	Chronic Myeloge...	Nilotinib	18 Years -	Novartis
Efficacy and Safety of AMN107 in Patients With GastroIntestinal Stromal Tumors (GIST) Who Have Failed Both Imatinib and Sunitinib	NCT00718562	Gastrointestina...	AMN107	20 Years -	Novartis
Trial Evaluating Nilotinib as Treatment for Newly Diagnosed CML Patients in Accelerated Phase.	NCT01605981	Chronic Myeloid...	AMN107	18 Years -	Novartis
Trial Evaluating Nilotinib as Treatment for Newly Diagnosed CML Patients in Accelerated Phase.	NCT01605981	Chronic Myeloid...	AMN107	18 Years -	Novartis
Efficacy and Safety of Oral AMN107 in Adults With Chronic Myelogenous Leukemia Resistant and/or Intolerant to Imatinib Mesylate Therapy	NCT00264160	Leukemia, Myelo...	AMN107	18 Years -	Novartis
Study of AMN107 With Imatinib in Gastrointestinal Stromal Tumors (GIST)	NCT00135005	Gastrointestina...	AMN107, STI571	18 Years -	Novartis
A Study of Nilotinib Versus Imatinib in GIST Patients	NCT00785785	Gastrointestina...	Nilotinib (AMN1... imatinib (STI57...	18 Years -	Novartis

Spots Global Cancer Trial Database for amn107

Every month we try and update this database with for amn107 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for amn107

Every month we try and update this database with for amn107 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for amn107 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.