Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Neoplasms by Histologic Type

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Azacitidine

Decitabine

Ponatinib

Sorafenib

Quizartinib

Crenolanib

Antimetabolites

Enzyme Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Cohort #1: Participants with no previous leukemia therapy (including no previous FLT3 inhibitor therapy) for either: a) front-line treatment of elderly (age 65 and greater) FLT3-mutated AML patients, or b) patients unable or unwilling to receive standard intensive therapy.

Part 1: Ponatinib at starting dose of 30 mg by mouth every day for one 28 day cycle. If disease does not respond to ponatinib alone, participant continues on to Part 2 of study.

Part 2 Phase I Dose Escalation: Ponatinib at starting dose of 30 mg by mouth every day of a 28 day cycle. 5-azacytidine at dose of 75 mg/m2/d administered subcutaneously (SQ) or intravenously (IV) for on Days 1-7 of every 28 day cycle.

Part 2 Phase II Dose Expansion: Ponatinib at maximum tolerated dose from Phase I by mouth every day of a 28 day cycle. 5-azacytidine 75 mg/m2/d administered subcutaneously (SQ) or intravenously (IV) on Days 1-7 of every 28 day cycle.

Cohort #2: Participants with relapsed/refractory FLT3-mutated AML that have not received prior FLT3 inhibitor therapy.

Part 1: Participants receive Ponatinib at starting dose of 30 mg by mouth every day for one 28 day cycle. If disease does not respond to ponatinib alone, participant continues on to Part 2 of study.

Part 2 Phase I Dose Escalation: Ponatinib at starting dose of 30 mg by mouth every day of a 28 day cycle. 5-azacytidine at dose of 75 mg/m2/d administered subcutaneously (SQ) or intravenously (IV) for on Days 1-7 of every 28 day cycle.

Part 2 Phase II Dose Expansion: Ponatinib at maximum tolerated dose from Phase I by mouth every day of a 28 day cycle. 5-azacytidine 75 mg/m2/d administered subcutaneously (SQ) or intravenously (IV) on Days 1-7 of every 28 day cycle.

Cohort #3: Participants with relapsed/refractory FLT3-mutated AML, that have received previous FLT3 inhibitor therapy (including, but not limited to, quizartinib, crenolanib, sorafenib, other FLT3 inhibitors).

Part 1: Participants receive Ponatinib at starting dose of 30 mg by mouth every day for one 28 day cycle. If disease does not respond to ponatinib alone, participant will continue on to Part 2 of study.

Part 2 Phase I Dose Escalation: Ponatinib at starting dose of 30 mg by mouth every day of a 28 day cycle. 5-azacytidine at dose of 75 mg/m2/d administered subcutaneously (SQ) or intravenously (IV) for on Days 1-7 of every 28 day cycle.

Part 2 Phase II Dose Expansion: Ponatinib at maximum tolerated dose from Phase I by mouth every day of a 28 day cycle. 5-azacytidine 75 mg/m2/d administered subcutaneously (SQ) or intravenously (IV) on Days 1-7 of every 28 day cycle.

Part 1: Ponatinib at starting dose of 30 mg by mouth every day for one 28 day cycle.

Part 2 Phase I Dose Escalation: Ponatinib at starting dose of 30 mg by mouth every day of a 28 day cycle.

Part 2 Phase II Dose Expansion: Ponatinib at maximum tolerated dose from Phase I by mouth every day of a 28 day cycle.

Part 2 Phase I Dose Escalation: 5-azacytidine at dose of 75 mg/m2/d administered subcutaneously (SQ) or intravenously (IV) for on Days 1-7 of every 28 day cycle.

Part 2 Phase II Dose Expansion: 5-azacytidine 75 mg/m2/d administered subcutaneously (SQ) or intravenously (IV) on Days 1-7 of every 28 day cycle.

5-azacytidine

About 30 days after end-of-study visit, study staff calls participant and asks if they have had any side effects and/or started any new treatment(s).

If disease appears to be responding to study drugs, study staff calls participant every 3-6 months for up to 5 years and asks how they are doing and about any side effects they may be having.

Phone Calls

Naval Daver, MD

The goal of Part 1 of this clinical research study is to learn if ponatinib alone can help to control FLT3-mutated AML or FLT3-mutated high-risk MDS. The safety of this drug will also be studied.

The goal of Part 2 of this clinical research study is to find the highest tolerable dose of ponatinib in combination with 5-azacytidine and to learn if the highest dose level found can help to control FLT3-mutated AML or FLT3-mutated high-risk MDS. The safety of this combination will also be studied.

Study Groups:

If participant is found to be eligible to take part in this study, they will be assigned to either Part 1 or Part 2 based on when they join this study.

If participant is enrolled in Part 1, they will receive ponatinib alone for the first cycle. If the doctor thinks it is needed, the dose level may be increased. If the disease does not respond to ponatinib alone, participant will continue on to Part 2 of this study.

Part 2 of this clinical research study will have 2 phases: Phase 1 (dose escalation) and Phase 2 (dose expansion).

In Part 2, participant will be assigned to a study group based on when they join this study. Up to 3 groups of 30 participants will be enrolled in Phase 1 of Part 2, and up to 60 participants will be enrolled in Phase 2.

If participant is enrolled in Phase 1, the dose of ponatinib they receive will depend on when they join this study. The first group of participants will receive the lowest dose level of ponatinib. Each new group will receive a higher dose of ponatinib than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of ponatinib is found.

If participant is enrolled in Phase 2, they will receive ponatinib at the highest dose that was tolerated in Phase 1.

All participants in Part 2 will receive the same dose level of 5-azacytidine.

Study Drug Administration:

Each study cycle is 28 days.

Participant will take ponatinib tablets by mouth 1 time every day while they are on study. Participant should swallow the tablets whole. Participant should not crush them.

If participant is enrolled in Part 2, they will receive 5-azacytidine either by vein over about 1 hour or as an injection under the skin on Days 1-7 of each study cycle or on Days 1-5, 8, and 9 of each study cycle (if the clinic is closed on a weekend).

If the doctor thinks it is needed, the dose level, dosing schedule, or study cycle may be changed and/or delayed. The study doctor will discuss any changes with participant.

Study Visits:

On Day 1 of each cycle (+/- 4 days), participant will have a physical exam.

On Day 1 (+/-1 day) of Cycles 1-3 and then every 3 cycles after that (Cycles 6, 9, 12, and so on), participant will have an EKG.

On Day 1 of Cycle 2 and then every 3 cycles after that, participant will have an ECHO or MUGA performed.

One (1) time each week during Cycles 1-3 and then 1 time every 2-4 weeks after that, blood (about 1 tablespoon) will be drawn for routine tests. Participant may be able to have these blood draws performed at a local lab or clinic that is closer to their home. The results of the testing will be sent to MD Anderson for review.

On Day 28 (+/- 7 days) of Cycles 1, 3, and then every 1-3 cycles after that, participant will have a bone marrow aspiration/biopsy to check the status of the disease.

One (1) time every 3 cycles, if participant can become pregnant, blood (about 1-2 tablespoons) will be drawn for a pregnancy test.

At any time while participant is on study, if the doctor thinks it is needed:

* Blood (about 1-2 tablespoons) will be drawn for routine tests.
* Participant may have a bone marrow aspiration/biopsy to check the status of the disease.

Length of Study:

Participant will receive ponatinib alone or ponatinib and 5-azacytidine for as long as the doctor thinks it is in their best interest. Participant will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if they are unable to follow study directions.

Patient's participation on the study will be over after the follow-up visits.

End-of-Study Visit:

Within 14 days after participant's last dose of study drug(s):

* Participant will have a physical exam.
* Blood (about 2-3 tablespoons) will be drawn for routine tests.
* If the doctor thinks it is needed, participant will have a bone marrow aspirate/biopsy to check the status of the disease.

Follow-Up:

About 30 days after the end-of-study visit, a member of the study staff will call participant to ask if they have had any side effects and/or started any new treatment(s). This call should last about 5 minutes. If the study staff thinks it is needed, participant may also be asked to come into the clinic for a physical exam.

Long-Term Follow-Up:

If the disease appears to be responding to the study drugs, a member of the study staff will call participant every 3-6 months for up to 5 years to ask how they are doing and about any side effects they may be having. Each call should last about 5 minutes. Participant may also be asked to come into the clinic for a physical exam, if the study staff thinks it is needed.

This is an investigational study. 5-azacytidine is FDA approved and commercially available for the treatment of myelodysplastic syndrome (MDS). Ponatinib is commercially available and FDA approved for the treatment of specific groups of chronic myeloid leukemia (CML) participants. Their use in this study is considered investigational. The study doctor can explain how the study drugs are designed to work.

Up to 132 participants will take part in this study. All will be enrolled at MD Anderson.

Dose-Escalation Study of Ponatinib, a FLT3 Inhibitor, With and Without Combination of 5-Azacytidine, in Patients With FLT3-Mutated Acute Myeloid Leukemia (AML)

Phase I/II, Dose-Escalation Study of Ponatinib, a FLT3 Inhibitor, With and Without Combination of 5-Azacytidine, in Patients With FLT3-Mutated Acute Myeloid Leukemia (AML)

MTD defined as highest dose level with \</= 1 out of 6 patients experience a dose limiting toxicity (DLT) during the first 28 days of treatment. DLT defined as clinically significant non-hematologic adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications.

CRc defined as complete remission (CR), complete remission with incomplete platelet recovery (CRp), or complete remission with incomplete blood count recovery (CRi). Response defined by achievement of CRc at any point in time within the first 3 cycles of therapy, or prior to going off study, for those patients discontinuing treatment before completion of 3 cycles of therapy.

Ariad Pharmaceuticals

M.D. Anderson Cancer Center

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Myeloproliferative Disorders

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

Ponatinib at a dose of 45 mg orally, once daily. If a dose is missed or vomited, the next dose should not be increased to account for missing a dose. Total duration of therapy 3 to 5 years.

Ponatinib at a dose of 30 mg orally, once daily. If a dose is missed or vomited, the next dose should not be increased to account for missing a dose. Total duration of therapy 3 to 5 years.

Starting dose: 45 mg by mouth once daily.

Jorge Cortes, MD

The goal of this clinical research study is to learn if ponatinib can help to control Chronic Myeloid Leukemia (CML) in accelerated phase. The safety of this drug will also be studied.

Ponatinib is designed to block the function of BCR-ABL, which is the abnormal protein responsible for causing leukemia in certain cells.

Ponatinib may cause a blood clot to form in an artery or in a vein. Depending on the location of the clot, this could cause a heart attack, a stroke, severe damage to other tissue, or death. A blood clot may occur within 2 weeks after you start taking the drug. About 25% (1 in 4) of patients taking the drug form an abnormal clot. Blood clots can occur in patients that do not have other known risk factors for forming clots. If you develop a blood clot, you will need to stop taking ponatinib. In some cases, emergency surgery could be needed to remove the clot and restore blood flow.

Study Drug Administration:

You will take ponatinib by mouth 1 time every day while you are on study with about a cup (8 ounces) of water. You should not eat within 2 hours before or after taking the drug. You will complete a study diary in which you will record the date and time that you take the study drug each time. If you miss any doses, you will also note this in the study diary. Bring this diary to every study visit, as described below.

Study Visits:

The tests and procedures for this study have a wide range of time in which they can be done. In general, your schedule of study visits will be as follows:

* Weekly in Month 1
* Monthly in Year 1
* Three (3) to 4 times in Year 2
* Two (2) to 3 times in every year after that

The study staff will help you schedule your study visits. The following tests and procedures will be performed:

* Every 1-2 weeks for the first 4 weeks, then every 4-6 weeks for the first year, then every 3-4 months for the next year, then every 4-6 months after that, blood (about 1/2 tablespoon) will be drawn for routine tests.
* Every 3 months for the first year, you will have an ECG.
* Every 3 months for the first year, then every 6-12 months after that, you will have a physical exam.
* Every 3-4 months for the first year, then every 6-12 months after that, blood (about 2 teaspoons) will be drawn to measure levels of leukemia cells in your body.
* Every 3-4 months for the first year, then every 6-12 months for the next 2 years, then every 2-3 years after that, you will have a bone marrow aspirate for genetic testing and to check the status of the disease.

Length of Participation:

You may continue taking the study drug for up to 5 years. You will be taken off study early if intolerable side effects occur, if the disease gets worse, or if you are unable to follow study directions.

Your participation on the study will be over when you have completed the follow-up visit/call.

Follow-Up:

If you leave the study, you will be called or you will come to the clinic within 30 days to learn about any side effects or symptoms you may be having. If you are called, this call will last about 2-3 minutes.

This is an investigational study. Ponatinib is FDA approved to treat patients with certain types of leukemia. Its use in this study is investigational.

Up to 80 patients will take part in this study. All will be enrolled at MD Anderson.

Participants enrolled before July 25, 2013 were given a starting dose of 45 mg per day. The study was amended and the dose was lowered due to tolerability. Participants enrolled after this date were given a starting dose of 30 mg per day.

Ponatinib - Frontline for Chronic Myeloid Leukemia (CML) in Accelerated Phase (AP)

Ponatinib as Initial Therapy for Patients With Chronic Myeloid Leukemia in Accelerated Phase

Proportion of participants with previously-untreated accelerated phase CML attaining complete cytogenetic response (CCyR) at 6 months of treatment with Ponatinib classified according to suppression of the Philadelphia chromosome (Ph) by cytogenetics (FISH if cytogenetic analysis not informative, e.g., insufficient metaphases). CCyR defined as Ph positive 0%.

Proportion of participants with previously-untreated accelerated phase CML receiving treatment of Ponatinib achieving a Complete cytogenetic response (CCyR). Classified according to suppression of the Philadelphia chromosome (Ph) by cytogenetics (FISH if cytogenetic analysis not informative, e.g., insufficient metaphases. CCyR is defined as Ph positive 0%.

Time to toxicity monitoring defined as any grade 3 or 4 drug-related non-hematologic adverse event that has not resolved to grade 2 or less after 6 weeks of optimal therapeutic management, or drug-related toxicity of any grade that in the opinion of the investigator prevents further therapy with ponatinib. Time to toxicity monitored using the Bayesian method of Thall, et al.

Ponatinib 45 mg

Ponatinib 30 mg

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Jorge Cortes, MD/Professor, Leukemia

Ponatinib 45 mg orally, once daily. Dose escalation to 30 mg possible for participants with adverse events.

Ponatinib 30mg orally, once daily. Dose escalation to 30 mg possible for participants with adverse events.

Number of Participants With Complete Cytogenetic Response (CCyR)

Elevated Amylase

Lipase Elevation

Pancreatitis

Abdominal Pain

Hypertension

Elevated alanine aminotransferase (ALT)

One participant was not included in analysis.

Toxicity Profile: Most Common Grade 3-4 Non-Hematologic Adverse Events (AEs) Seen in More Than 1 Participant

Overall Study

Gland and Hormone Related Diseases

Thyroid Neoplasms

Thyroid Diseases

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Thyroid Cancer, Medullary

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Rearranged during transfection (RET) mutation positive

Rearranged during transfection (RET) mutation negative

Ponatinib tablets will be administered orally, continually, once daily at a dose of 30 mg. A cycle of ponatinib is defined as 28 consecutive days starting with the first day of the treatment cycle. Treatment will be administered primarily in an outpatient setting.

James Gulley, M.D.

Background:

* Medullary thyroid cancer (MTC) represents 5% of thyroid cancers and presents as a hereditary (25% of cases) or sporadic (75% of cases) neuroendocrine malignancy.
* MTC arises from the parafollicular C-cells of the thyroid.
* Germline mutations in the rearranged during transfection (RET) proto-oncogene occur in virtually all of hereditary MTC cases, and somatic RET mutations occur in 50% of sporadic cases.
* Drugs targeting RET kinase such as vandetanib and cabozantinib have shown efficacy in the treatment of advanced or metastatic MTC, however, more effective RET inhibitors are needed for previously untreated patients as well as patients who have become refractory to other molecular targeted therapeutics (MTTs).
* Ponatinib, a drug that is Food and Drug Administration (FDA) approved as a therapy for chronic myelogenous leukemia

(CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), is a potent inhibitor of RET kinase.

Primary Objective:

-To determine the objective overall response rate (complete response \[CR\] + partial response

\[PR\] by Response Evaluation Criteria in Solid Tumors (RECIST) to ponatinib in the treatment of patients with advanced or metastatic MTC previously treated with cabozantinib and vandetanib who: 1) have tumors with RET mutations and 2) have tumors without RET mutations.

Eligibility:

* Patients must have histologically confirmed, unresectable, locally advanced or metastatic MTC, with measurable disease by RECIST criteria.
* Patients must have disease amenable to biopsy and be willing to undergo biopsy for molecular analysis, and also have adequate archival material from their thyroidectomy or from a tumor biopsy obtained prior to beginning any systemic therapy.
* Patients must have failed or been intolerant to prior treatment with both cabozantinib and vandetanib.
* The last dose of prior systemic therapy must be more than 28 days prior to the first dose of ponatinib
* Radiation therapy is permitted if the last treatment was received more than 28 days prior to the first dose of ponatinib.

Design:

* Open label phase II trial with 2 treatment groups:
* RET mutation positive MTC, previously treated with vandetanib and cabozantinib
* RET mutation negative MTC, previously treated with vandetanib and cabozantinib
* Patients will receive ponatinib 30 mg orally daily until disease progression or until the development of intolerable side effects.
* Tumor response will be assessed by RECIST 1.1 criteria at 8 weeks and then every 12 weeks thereafter. After one year on study, tumor response will be assessed every 16 weeks.
* Patients will have a biopsy of their MTC for molecular analysis prior to initiating treatment with ponatinib. Patients will also have a biopsy of their MTC at the time of tumor progression, should that occur.

Background:

* Medullary thyroid cancer (MTC) represents 5% of thyroid cancers and presents as a hereditary (25% of cases) or sporadic (75% of cases) neuroendocrine malignancy.
* MTC arises from the parafollicular C-cells of the thyroid.
* Germline mutations in the rearranged during transfection (RET) proto-oncogene occur in virtually all of hereditary MTC cases, and somatic RET mutations occur in 50% of sporadic cases.
* Drugs targeting RET kinase such as vandetanib and cabozantinib have shown efficacy in the treatment of advanced or metastatic MTC, however, more effective RET inhibitors are needed for previously untreated patients as well as patients who have become refractory to other molecular targeted therapeutics (MTTs).
* Ponatinib, a drug that is Food and Drug Administration (FDA) approved as a therapy for chronic myelogenous leukemia

(CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), is a potent inhibitor of RET kinase.

Primary Objective:

-To determine the objective overall response rate (complete response \[CR\] + partial response \[PR\] by Response Evaluation Criteria in Solid Tumors (RECIST) to ponatinib in the treatment of patients with advanced or metastatic MTC previously treated cabozantinib and vandetanib who: 1) have tumors with RET mutations and 2) have tumors without RET mutations.

Eligibility:

* Patients must have histologically confirmed, unresectable, locally advanced or metastatic MTC, with measurable disease by RECIST criteria.
* Patients must have disease amenable to biopsy and be willing to undergo biopsy for molecular analysis, and also have adequate archival material from their thyroidectomy or from a tumor biopsy obtained prior to beginning any systemic therapy.
* Patients must have failed or been intolerant to prior treatment with both cabozantinib and vandetanib.
* The last dose of prior systemic therapy must be more than 28 days prior to the first dose of ponatinib.
* Radiation therapy is permitted if the last treatment was received more than 28 days prior to the first dose of ponatinib.

Design:

* Open label phase II trial with 2 treatment groups:
* RET mutation positive MTC, previously treated with vandetanib and cabozantinib
* RET mutation negative MTC, previously treated with vandetanib and cabozantinib
* Patients will receive ponatinib 30 mg orally daily until disease progression or until the development of intolerable side effects.
* Tumor response will be assessed by RECIST 1.1 criteria at 8 weeks and then every 12 weeks thereafter. After one year on study, tumor response will be assessed every 16 weeks.
* Patients will have a biopsy of their MTC for molecular analysis prior to initiating treatment with ponatinib. Patients will also have a biopsy of their MTC at the time of tumor progression, should that occur.

Ponatinib for Advanced Medullary Thyroid Cancer

A Phase II Study of Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer

Defined as the percentage of participants with a best response (complete response (CR) + partial response (PR)) recorded from the start of the treatment until disease progression/recurrence assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is the disappearance of all target lesions. Any pathological lymph nodes (Whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

Progression free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

Compare the molecular profile of tumor deoxyribonucleic acid (DNA) prior to treatment with the molecular profile at the time of progression. Prior to the first dose of ponatinib and at time of progression, subjects were to undergo a biopsy of the primary tumor or any metastatic site for analysis of tumor DNA for rearranged during transfection (RET) or rat sarcoma (RAS) mutation. Progression is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is defined as at least a 20% decrease in the sum of diameters of target lesions, taking as reference the smallest sum on study.

Responders are those subjects with a best biomarker response of complete response (CR) or partial response (PR) and who achieve a clinical response of CR or PR assessed by the following criteria. Biomarker: complete response (CR) is normalization (\</= upper limit of normal (ULN)) of CTN (i.e., normal \<10 pg/mL) following treatment, confirmed with a repeat CTN level at least 4 weeks apart. Partial response (PR) is a \>/=50% decrease in the CTN level relative to baseline level, confirmed with a repeat CTN level at least 4 weeks apart. Clinical: complete response (CR) is an average of 0-2 formed stools per day for a period of at least 4 weeks. Partial response (PR) is a \>50% decrease in the average stool frequency relative to baseline and a change in stool consistency from watery to loose (partially formed) for a period of at least 4 weeks.

Objective response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is the disappearance of all target lesions. Any pathological lymph nodes (Whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. Stable disease (SD) is neither shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Responders are those subjects with a best biomarker response of complete response (CR) or partial response (PR) and who achieve a clinical response of CR or PR assessed by the following criteria. Biomarker: complete response (CR) is normalization (\</= upper limit of normal (ULN)) of CTN (i.e., normal 0-2.5 mcg/L) following treatment, confirmed with a repeat CEA level at least 4 weeks apart. Partial response (PR) is a \>/=50% decrease in the CEA level relative to baseline level, confirmed with a repeat CEA level at least 4 weeks apart. Clinical: complete response (CR) is an average of 0-2 formed stools per day for a period of at least 4 weeks. Partial response (PR) is a \>50% decrease in the average stool frequency relative to baseline and a change in stool consistency from watery to loose (partially formed) for a period of at least 4 weeks.

Overall survival is defined as the time between the first day of treatment to the day of disease progression.

National Cancer Institute (NCI)

National Institutes of Health Clinical Center (CC)

Principal Investigator

No participants were enrolled in the RET mutation negative group; study closed prematurely.

Rearranged during transfection) (RET)

Ponatinib: Ponatinib tablets will be administered orally, continually, once daily at a dose of 30 mg. A cycle of ponatinib is defined as 28 consecutive days starting with the first day of the treatment cycle. Treatment will be administered primarily in an outpatient setting.

RET Mutation Positive Participants

Rearranged during transfection (RET)

Ponatinib: Ponatinib tablets will be administered orally, continually, once daily at a dose of 30 mg. A cycle of ponatinib is defined as 28 consecutive days starting with the first day of the treatment cycle. Treatment will be administered primarily in an outpatient setting.

Age, Categorical

Gender

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Dr. James Gulley

Complete Response

Partial Response

Overall Response Rate.

Progression Free Survival

Number of Participants With Adverse Events

RET mutation

RAS mutation

Although molecular profiling was to be completed prior to first dose of ponatinib and at time of progression, samples were tested on arrival only as mutational status was an eligibility requirement. No participants were enrolled in the RET mutation negative group; study closed prematurely.

Molecular Differences in Advanced Medullary Thyroid Cancer (MTC)

None of the participants achieved a clinical response and no data were collected for this assessment. No participants were enrolled in the RET mutation negative group; study closed prematurely.

Changes in Serum Levels of MTC Tumor Markers Calcitonin (CTN) and Its Relation With Clinical Response

Complete Response (CR)

Partial Response (PR)

Progressive Disease (PD)

Stable Disease (SD)

One participant died on study during cycle 2. No participants were enrolled in the RET mutation negative group; study closed prematurely.

Objective Response to Ponatinib

Changes in Serum Levels of MTC Tumor Markers Carcinoemybryonic Antigen (CEA) and Its Relation With Clinical Response

Overall Survival

RET Mutation Positive Participants.

Blast Crisis

Cell Transformation, Neoplastic

Carcinogenesis

Neoplastic Processes

This is an observational registry to further characterize the safety profile of patients with chronic myeloid leukemia in the chronic phase (CP-CML), accelerated phase (AP-CML), blast phase (BP-CML), or Ph+ALL treated with Iclusig (ponatinib) in routine clinical practice in the US. The registry is focused on analysis of vascular occlusive events.

The registry is being conducted in an effort to better understand rates, risk factors, and outcomes associated with vascular occlusive events in patients treated with Iclusig (ponatinib) in real world settings. This registry study will collect information about patient demographics, leukemia diagnosis, previous anti-cancer treatments, history of cardiovascular disease, risk factors for vascular complications, and concurrent medications (including antiplatelet and/or anticoagulant agents).

An Observational Registry to Evaluate the Incidence of and Risk Factors for Vascular Occlusive Events Associated With ICLUSIG®

A Postmarketing Observational Registry to Evaluate the Incidence of and Risk Factors for Vascular Occlusive Events Associated With ICLUSIG® (Ponatinib) in Routine Clinical Practice in the United States (OMNI).

All VOEs will be entered into the EDC (Electronic Data Capture system)

Subject medical history and family medical history will be entered into the EDC

The category/type of outcome (e.g. Death, Disability/Permanent Damage, Hospitalization, Other), the time of duration, and status (continuing, resolved, fatal) will be entered into the EDC.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Dose-Escalation Study of Ponatinib, a FLT3 Inhibitor, With and Without Combination of 5-Azacytidine, in Patients With FLT3-Mutated Acute Myeloid Leukemia (AML)	NCT02829840	Leukemia FLT3-Mutated Ac... FLT3-Mutated Hi...	Ponatinib 5-azacytidine Phone Calls	18 Years -	M.D. Anderson Cancer Center
Ponatinib - Frontline for Chronic Myeloid Leukemia (CML) in Accelerated Phase (AP)	NCT01570868	Leukemia	Ponatinib	18 Years -	M.D. Anderson Cancer Center
Ponatinib for Advanced Medullary Thyroid Cancer	NCT01838642	Thyroid Neoplas...	Ponatinib	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
An Observational Registry to Evaluate the Incidence of and Risk Factors for Vascular Occlusive Events Associated With ICLUSIG®	NCT02455024	Myeloid Leukemi...		18 Years -	Takeda
An Observational Registry to Evaluate the Incidence of and Risk Factors for Vascular Occlusive Events Associated With ICLUSIG®	NCT02455024	Myeloid Leukemi...		18 Years -	Takeda
Ponatinib for Advanced Medullary Thyroid Cancer	NCT01838642	Thyroid Neoplas...	Ponatinib	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
Ponatinib - Frontline for Chronic Myeloid Leukemia (CML) in Accelerated Phase (AP)	NCT01570868	Leukemia	Ponatinib	18 Years -	M.D. Anderson Cancer Center
Ponatinib - Frontline for Chronic Myeloid Leukemia (CML) in Accelerated Phase (AP)	NCT01570868	Leukemia	Ponatinib	18 Years -	M.D. Anderson Cancer Center
An Observational Registry to Evaluate the Incidence of and Risk Factors for Vascular Occlusive Events Associated With ICLUSIG®	NCT02455024	Myeloid Leukemi...		18 Years -	Takeda
Dose-Escalation Study of Ponatinib, a FLT3 Inhibitor, With and Without Combination of 5-Azacytidine, in Patients With FLT3-Mutated Acute Myeloid Leukemia (AML)	NCT02829840	Leukemia FLT3-Mutated Ac... FLT3-Mutated Hi...	Ponatinib 5-azacytidine Phone Calls	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for ap24534

Every month we try and update this database with for ap24534 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 ap24534

Every month we try and update this database with for ap24534 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 ap24534 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.