Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

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

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Ponatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

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.

Ariad Pharmaceuticals

M.D. Anderson Cancer Center

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

Heart and Blood Diseases

Substance Related Disorders

Wounds and Injuries

Skin and Connective Tissue Diseases

Cardiomyopathies

Systolic Murmurs

Cardiotoxicity

Osteosarcoma

Heart Diseases

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Sarcoma

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Doxorubicin Induced Cardiomyopathy

Soft Tissue Sarcoma

CMR T1 mapping, T2mapping, T2\* mapping, LGE, ECV

contrast-enhanced cardiac magnetic resonance imaging(MAGNETOM Aera 1.5T)

ELOY YIN WANG, Master

ZHAOMING YE, Doctor

using a contrast-enhanced (CE) cardiac magnetic resonance imaging(CMR) which included the measurement of T1 mapping, T2 mapping, T2\* mapping and late gadolinium enhancement(LGE) sequences, as well as LVEF and extracellular volume(ECV) to evaluate the respective changes before and after anthracycline chemotherapy.

Osteosarcoma is the most common primary malignant bone tumor in children and young adults and accounts for 5% of all pediatric malignancies. The long-standing chemotherapy regimen of doxorubicin and cisplatin with or without methotrexate remains a standard treatment of osteosarcoma.But anthracyclines such as doxorubicin have a notorious cardiotoxic side effect, which causes chemotherapy-related cardiac dysfunction(CTRCD). The American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI) defines it as a decrease in left ventricular ejection fraction (LVEF) of more than 10% to below the lower limit of normal, which is considered an LVEF of 53%, despite symptoms.

Cardiac magnetic resonance imaging is the gold standard for detection of ventricular volume and function. The parametric mapping techniques provide a non-invasive tool for quantifying tissue alterations in myocardial disease and is capable of in vivo tissue characterization.

In this study, the investigators used a contrast-enhanced (CE) cardiac magnetic resonance imaging(CMR), which included the measurement of T1 mapping, T2 mapping, T2\* mapping and late gadolinium enhancement(LGE) sequences, as well as LVEF and extracellular volume(ECV) to evaluate the respective changes before and after anthracycline chemotherapy.

Study Population:

This prospective study was conducted at the Second Affiliated Hospital, School of Medicine, Zhejiang University. All chemotherapy naive patients whose biopsy results show high grade osteosarcoma were considered. Patients with underlying heart disease, severe hypertension, diabetes mellitus and previous history of gadolinium contrast agent allergy were excluded.Patients were treated with a standard chemotherapy protocol containing anthracyclines.

Study Protocol:

All patients underwent a contrast-enhanced (CE) cardiac magnetic resonance imaging(CMR), including measurement of LVEF, T1mapping, T2mapping, T2\*mapping, ECV, LGE before starting chemotherapy (baseline), after neoadjuvant chemotherapy treatment, at the end of treatment (within 1 month), or whenever required by the clinical situation. These times points corresponded to scheduled oncological controls.

The CMR protocol included a standard segmented cine steady-state free-precession sequence, a T2 gradient spin-echo mapping sequence, a T2\* gradient spin-echo mapping sequence, native and post-contrast T1 mapping sequences, and late gadolinium enhancement (LGE) sequence. The imaging parameters for the standard segmented cine steady-state free-precession sequence were as follows: field of view (FOV) 340 X340 mm², slice thickness 8 mm , repetition time (TR) 34.84ms, echo time (TE) 1.14ms, flip angle 67°, voxel size 1.8 X1.8 mm, and number of excitation. The imaging parameters for the T2-gradient-spin-echo mapping sequence were FOV 340X 340 mm², acquisition voxel size 1.8 X1.8 mm², slice thickness 8 mm, 8 echo times ranging from 6.7 to 53.6ms, and flip angle 70°. The T2\* mapping sequence parameter were FOV 340X340 mm², acquisition voxel size 1.3X1.3mm², slice thickness 8mm, 8 echo times ranging from 2.22 to 17.48 (2.22,4.4,6.58,8.76,10.94,13.12,15.3,17.48), and flip angle 20°. The T1 mapping sequence (Modified Look-Locker Inversion recovery \[MOLLI\]) was acquired before and 10 min after contrast administration. All MOLLI sequences were based on a 5(3)3 scheme using a single shot steady-state free precession readout sequence (TR/TI/TE/flip angle 291.84ms/183ms/1.22ms/35°) with an in-plane acquisition resolution of 1.2 X1.2 mm² and an 8mm slice thickness. LGE imaging was performed 8 min after intravenous administration of 0.2mmol/kg gadopentetate dimeglumine contrast agent using a 3-dimensional inversion-recovery spoiled turbo field echo sequence (TR/TE/flip angle 813.6ms/1.09ms/40). Inversion time was adjusted before acquisition using a look-locker scout sequence with different inversion times to ensure proper nulling of the healthy myocardium signal.

The primary end point of the study was completion of chemotherapy with anthracycline drugs.

The secondary end point was cardiotoxicity. The time of occurrence of cardiotoxicity was recorded. Cardiotoxicity was defined as an LVEF reduction \>10% from baseline, or LVEF \<53%.

The following cardiac events were also considered as secondary end points: cardiac death, acute coronary syndromes, acute pulmonary edema, overt HF, and life-threatening arrhythmias.

Evaluation of Myocardial Injury After Anthracycline Chemotherapy in Osteosarcoma Patients Using CMR

Change in T1 mapping values before and after anthracyclin chemotherapy

Change in T2 mapping values before and after anthracyclin chemotherapy

Change in T2\* mapping values before and after anthracyclin chemotherapy

Cancer therapy-related cardiac dysfunction was defined as an LVEF reduction \>10% from baseline, or LVEF \<53%

Second Affiliated Hospital, School of Medicine, Zhejiang University

Breast Neoplasms

Breast Diseases

Skin Diseases

Yvonne Koop, MSc

Saloua El Messaoudi, PhD

Angela Maas, PhD

Robin Nijveldt, PhD

With this study the investigators will assess early cardiac damage by means of Global Longitudinal Strain (GLS) in newly diagnosed breast cancer (BC) patients treated with anthracycline-based chemotherapy, and to investigate whether myocardial damage as measured with T1 / T2 Cardiovascular Magnetic Resonance (CMR) mapping and plasma hs-Troponin T is related to changes in GLS.

Early Detection of Cardiac Damage With CMR in Women With Breast Cancer

A relative reduction in Global Longitudinal Strain (GLS) assessed with CMR

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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
Evaluation of Myocardial Injury After Anthracycline Chemotherapy in Osteosarcoma Patients Using CMR	NCT04461223	Cardiotoxicity Osteosarcoma Myocardial Inju... Chemotherapy In... Doxorubicin Ind...	contrast-enhanc...	8 Years - 50 Years	Second Affiliated Hospital, School of Medicine, Zhejiang University
Ponatinib - Frontline for Chronic Myeloid Leukemia (CML) in Accelerated Phase (AP)	NCT01570868	Leukemia	Ponatinib	18 Years -	M.D. Anderson Cancer Center
Early Detection of Cardiac Damage With CMR in Women With Breast Cancer	NCT04046315	Cardiotoxicity Breast Cancer Chemotherapy In...	CMR	18 Years -	Radboud University Medical Center

Spots Global Cancer Trial Database for cmr

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

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