Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Philadelphia Chromosome

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Acute Graft Versus Host Disease

Lymphosarcoma

Chronic Myeloproliferative Disorders

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Nilotinib

Dasatinib

Ponatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

CP-CML participants R-I to dasatinib or nilotinib were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

CP-CML participants who had T315I mutation of breakpoint cluster region-Abelson complex (BCR-ABL) were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

AP-CML R-I to dasatinib or nilotinib were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

AP-CML participants who had T315I mutation of BCR-ABL were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

BP-CML or Ph+ ALL R-I to dasatinib or nilotinib or Ph+ ALL R-I to dasatinib or nilotinib were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

BP-CML or Ph+ ALL participants who had T315I mutation of BCR-ABL were administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

Participants who were not assigned to any of the cohorts and have no T315I mutation at study entry and were not R-I to dasatinib or nilotinib, administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

Medical Director Clinical Science

The purpose of this study is to determine the efficacy of ponatinib in patients with chronic myeloid leukemia (CML) in chronic phase (CP), accelerated phase (AP) or blast phase (BP) or with philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) who either are resistant or intolerant to either dasatinib or nilotinib, or have the (T)hreonine-315-(I)soleucine (T315I) mutation.

The preliminary analysis of the phase 1 clinical trial revealed evidence of clinical antitumor activity in patients with resistance to approved second-generation tyrosine kinase inhibitors (TKI), dasatinib and nilotinib, including patients with the T315I mutation of the BCR-ABL gene (BCR-ABL). This Phase 1 study, taken together with the strong preclinical data that characterize ponatinib, provides the rationale for moving to a pivotal phase 2 trial of this agent in a population of patients with chronic myeloid leukemia (CML) and Ph+ Acute Lymphoblastic Leukemia (ALL) who are resistant or intolerant to prior TKI therapy and in those patients with the T315I mutation.

PACE is a multi-center, international, phase 2, uncontrolled, open-label trial of oral ponatinib in patients with Philadelphia chromosome-positive (Ph+) disease. The study enrolled 449 patients. Participants assigned to 1 of 6 cohorts in accordance with disease group and received:

* Ponatinib 45 mg

This multi-center trial is conducted worldwide. The overall time to participate in this study is 96 months after last dose of study drug treatment.

Ponatinib for Chronic Myeloid Leukemia (CML) Evaluation and Ph+ Acute Lymphoblastic Leukemia (ALL)

A Pivotal Phase 2 Trial of Ponatinib (AP24534) in Patients With Refractory Chronic Myeloid Leukemia and Ph+ Acute Lymphoblastic Leukemia

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

MCyR is defined as percentage of participants with complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). Cytogenetic response is the percentage of Philadelphia chromosome positive (Ph+) metaphases in bone marrow (BM). Response is further defined as MCyR: CCyR or PCyR, where CCyR: no Ph+ cells; PCyR: 1 to 35% Ph+ cells.

MaHR is defined as percentage of participants with complete hematologic response (CHR) or no evidence of leukemia (NEL). Response criteria for CHR is reported as white blood cells (WBC)≤institutional upper limit of normal, absolute neutrophil count (ANC)≥1000/mm\^3, platelets≥100,000/mm\^3, no blasts or promyelocytes in peripheral blood, BM blasts ≤5%, \<5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood \<5%, no extramedullary involvement; Response criteria for NEL is reported as WBC≤institutional upper limit of normal, no blasts or promyelocytes in peripheral blood, BM blasts ≤5%, \<5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood \<5%, no extramedullary involvement, at least 1 of the following: (i) 20,000/mm\^3≤platelets\<100,000/mm\^3; (ii) 500/mm\^3≤ANC\<1000/mm\^3.

MaHR is defined as percentage of participants with CHR or NEL. Response criteria for CHR is reported as WBC≤institutional upper limit of normal, ANC≥1000/mm\^3, platelets ≥100,000/mm\^3, no blasts or promyelocytes in peripheral blood, BM blasts ≤5%, \<5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood \<5%, no extramedullary involvement; Response criteria for NEL is reported as WBC≤ institutional upper limit of normal, no blasts or promyelocytes in peripheral blood, BM blasts ≤5%, \<5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood \<5%, no extramedullary involvement, at least 1 of the following: (i) 20,000/mm\^3 ≤platelets\<100,000/mm\^3; (ii) 500/mm\^3≤ANC\<1000/mm\^3.

Response criteria for CHR is reported as WBC≤institutional upper limit of normal, platelets\<450,000/mm\^3, no blasts or promyelocytes in peripheral blood, \<5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood \<5%, no extramedullary involvement (including no hepatomegaly or splenomegaly).

Confirmed MCyR is defined as 2 assessments of CCyR or PCyR at least 28 days apart. For CP participants entering the trial in PCyR, confirmed MCyR is defined as 2 assessments of CCyR at least 28 days apart.

MMR is defined as a ratio of reverse transcribed transcript of BCR-ABL to ABL ≤0.1% on the international scale (equivalent to a 3-log reduction in transcript).

MCyR is defined as percentage of participants with CCyR or PCyR. Cytogenetic response is the percentage of Ph+ metaphases in BM. Response is further defined as MCyR: CCyR or PCyR, where CCyR: no Ph+ cells; PCyR: 1 to 35% Ph+ cells.

Confirmed MCyR is defined as 2 assessments of CCyR or PCyR at least 28 days apart.

Time to response is defined as the interval from the first dose of study treatment until the criteria for response are first met, censored at the last assessment of response. Median time to response was estimated using the Kaplan-Meier method.

Duration of Response is defined as the interval between the first assessment at which the criteria for response are met until the criteria for progression are met, censored at the last date at which the criteria for response are met. Duration of response was estimated by the Kaplan-Meier method as the probability of remaining in response.

PFS is defined as the interval from the first dose of study treatment until the criteria for progression or death are met, censored at the last response assessment. Progression from CP is reported as death, development of AP or BP, loss of CHR (in the absence of cytogenetic response), confirmed by development in complete blood counts (CBCs) at least 4 weeks apart, loss of MCyR, increasing WBC in participant without CHR defined by doubling of WBC to \>20K on 2 occasions at least 4 weeks apart; Progression from AP is reported as death, development of confirmed BP, loss of previous major or minor hematologic response over a 2-week period, no decrease from baseline levels in percentage blasts in peripheral blood or BM on all assessments over a 4-week period; Progression from BP or Ph+ ALL is reported as death, increasing blasts in peripheral blood or BM over a 4 week period.

OS is defined as the interval from the first dose of study treatment until death, censored at the last date at which participant was known to be alive.

An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy.

Ariad Pharmaceuticals

At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Cohort A: CP-CML R-I

Cohort B: CP-CML With T315I Mutation

Cohort C: AP-CML R-I

Cohort D: AP-CML With T315I Mutation

Cohort E: BP-CML/Ph+ ALL R-I

Cohort F: BP-CML or Ph+ ALL With T315I Mutation

Unassigned AP/CP-CML

Participants who were not assigned to any of the cohorts and have no T315I mutation at study entry and were not resistant or intolerant to dasatinib or nilotinib, administered ponatinib 45 mg, tablet, orally, once daily until disease progression or development of intolerance or if they met one or more of the protocol defined criteria for discontinuation (Up to approximately 48 months).

Unassigned to Cohorts A-F

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

ECOG-PS measured on-therapy assessed participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (\>50% of waking hrs), capable of all self care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair \>50% of waking hrs; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=dead.

1 participant from the cohort F had missing ECOG data.

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

Time From Diagnosis to First Dose

The safety population included all participants who received at least 1 dose of ponatinib.

Medical Director

Treated population included all participants assigned to Cohorts A to F who received at least 1 dose of ponatinib. The data for this outcome measure is applicable for Cohorts A and B only.

Percentage of CP-CML Participants With Major Cytogenetic Response (MCyR)

Treated population included all participants assigned to Cohorts A to F who received at least 1 dose of ponatinib. The data for this outcome measure is applicable for Cohorts C and D only.

Percentage of AP-CML Participants With Major Hematologic Response (MaHR)

Treated population included all participants assigned to Cohorts A to F who received at least 1 dose of ponatinib. The data for this outcome measure is applicable for Cohorts E and F only.

Percentage of BP-CML/Ph+ ALL Participants With MaHR

Percentage of CP-CML Participants With CHR

Percentage of CP-CML Participants With Confirmed MCyR

Percentage of CP-CML Participants With Major Molecular Response (MMR)

Treated population included all participants assigned to Cohorts A to F who received at least 1 dose of ponatinib. The data for this outcome measure is applicable for Cohorts C to F only.

Percentage of AP-CML or BP-CML/Ph+ ALL Participants With MCyR

Percentage of AP-CML or BP-CML/Ph+ ALL Participants With Confirmed MCyR

Percentage of AP-CML or BP-CML/Ph+ ALL Participants With MMR

Hematologic Response

Cytogenetic Response

Molecular Response

Treated population included all participants assigned to Cohorts A to F who received at least 1 dose of ponatinib. Median time to response was reported for responders only. Participants who did not achieve the specified response were censored at the last response assessment. Number analyzed: participants with data available at given time-point.

Time to Response

Treated population included all participants assigned to Cohorts A to F who received at least 1 dose of ponatinib. Number analyzed is number of participants with data available for analysis at given time-point

Duration of Response

Treated population included all participants assigned to Cohorts A to F who received at least 1 dose of ponatinib.

Progression-free Survival (PFS)

Overall Survival (OS)

TEAE

Number of Participants With Treatment-Emergent Adverse Event (TEAE) and Serious AE (SAE)

Overall Study

Nutritional and Metabolic Diseases

Hypoxia

Disease Progression

Acidosis

Acidosis, Lactic

Signs and Symptoms, Respiratory

Acid-Base Imbalance

Metabolic Diseases

The purpose of this study is to analyze the gene expression patterns associated with various microenvironmental stresses in tumors to understand their roles in tumor progression and treatment responses. To achieve this goal, we will perform gene expression analysis of the tumor samples collected from an IRB-approved study (IRB #: 4516-05-2R2) International Phase III Study of Chemoradiotherapy versus Chemoradiotherapy Plus Hyperthermia for Locally Advanced Cervical Cancer directed by Dr. Mark Dewhirst. We will correlate the gene expression signatures of different microenvironmental stresses with the measured physiological parameters to understand their role in tumor progression, treatment response and clinical outcomes.

Jen-Tsan Chi, Ph.D.

In the first part of the proposal, we will determine the cellular responses to various microenvironmental factors (such as lactosis, acidosis, hypoxia, glucose deprivation) in cultured epithelial cells (commercially obtained) making use of DNA microarray analysis. From the analysis of these microarray assays, we will obtain the gene signatures reflecting how cells respond to these environments stresses. These gene signatures will be used to analyze and annotate the gene expression patterns in the tumor samples and whether hyperthermia will affect the physiological parameters and the corresponding gene signatures.

In the second part of the proposal, we will work with Dr. Dewhirst to perform gene expression study of cervical cancer samples from a phase III, multicenter, randomized clinical trial (IRB 4516-05-2R2). The subjects will de-identified and we will not obtain directly the PHI of the subjects in this trial. Subjects will be randomized to chemoradiotherapy alone or chemoradiotherapy + hyperthermia. For subjects randomized to hyperthermia, heat treatments will be administered concurrently with chemotherapy once weekly during the course of external beam radiation. In the hyperthermia suite, catheters will be placed in the cervical os, vagina and rectum for internal temperature monitoring. Hyperthermia will be given externally to the pelvis and abdomen using the BSD Sigma 60 ,Sigma Eye or Sigma Ellipse systems. Initial power will be limited to less than 1500 watts with phase and amplitude adjusted for equal surface electric fields in each quadrant of the applicator. Heating will continue for 60 minutes after average cervical os or interstitial temperatures of 40°C have been achieved, or for a maximum total duration of 90 minutes, whichever is longest. The bolus temperature will be 37° at initiation of power and will be reduced as necessary for patient comfort and/or to help maintain oral temperature of 38.5C. Power will also be reduced or treatment will be stopped at the patient request, or due to intractable pain, nausea or vomiting, if normal tissue temperature rises to 44°C, pulse \> 160, BP \> 180/100 or \< 90/50, altered mental status, or systemic temperature \> 38.5°C.

A. The research materials will include the tumor biopsy obtained before and after HT treatments to be used for gene expression studies as well as for the IHC and ISH studies to the findings from our microarray analysis. We will also obtain the information on the tumor physiological parameters information measured in these tumors.

B. The data of the tumor physiological parameters measured and the response to treatments and other clinical outcomes of these patients will also be acquired.

C. Only the physicians taking care of the patients will have access to the patient identifies and other Protected Health Information (PHI). All information will be de-identified and remain anonymous during the studies.

D. The specimens will be collected when the patients undergo medical care for their respective diseases. No new materials or data will need to be collected specifically for this proposal. These biopsies and physiological measurements are included in the original proposed clinical trials.

The Gene Expression Studies of the Role of Tumor Microenvironments in Tumor Progression

The Gene Expression Studies of Tumor Microenvironments and Their Roles in Tumor Progression

Duke University

Mouth and Tooth Diseases

Head and Neck Neoplasms

Xerostomia

Salivary Gland Diseases

Mouth Diseases

Stomatognathic Diseases

Herbal and Botanical

Hibiscus

Aqualief

Placebo

Ester Orlandi, MD

The treatment of xerostomia is aimed to increase existing saliva flow or replace lost secretions, the control of the state of oral health, the control of dental caries, and the treatment of possible infections.

Therapy options in xerostomia depend on the presence of residual secretion or the absence of it. When residual secretory capacity is present, it is advisable to regularly stimulate the salivary glands by mechanical or gustatory stimuli as supportive oral care.

Aqualief® is a food supplement based on carnosine and hibiscus. These two ingredients are mixed in specific proportions to form a pH buffering system which maintains the pH of the oral cavity at the proper value which is required for the regular secretion of saliva.

Xerostomia is the biggest and chronic side effect of the RT for head and neck cancer. To treat xerostomia different approach should be followed at the same time: to increase existing saliva flow or replace lost secretions, to control the state of oral health, to control dental caries and to treat possible infections18.

When residual secretory capacity is present, it is advisable to regularly stimulate the salivary glands by mechanical or gustatory stimuli as supportive oral care.

The salivary flow can be stimulated by the use of sugarless chewing gum or xylitol/sorbitol candy or through parasympathomimetic drug such as pilocarpine. Pilocarpine is a natural alkaloid that activates cholinergic receptors, authorized to treat xerostomia. Due to its main mechanism of action, pilocarpine has some muscarinic side effects19, especially vomiting, sweating, headache, increased urinary frequency, wheezing, watery eyes, nausea and gastrointestinal intolerance, hypotension, rhinitis, diarrhea, and visual disturbances. Pilocarpine has also some use restrictions that make it not prescribable to certain patients (patients with asthma, high blood pressure, heart diseases and in therapy with β-blockers cannot use pilocarpine because this drug is a nonselective antagonist of muscarinic receptors and, therefore, it can interfere with the cardiac and respiratory functions).

Acupuncture seems to alleviate radio-induced xerostomia but it mechanism of action is not totally clear and systematic reviews indicate its efficacy as doubtful20,21.

Other products are under investigation and their efficacy in xerostomia due to RT is still unclear.

Aqualief® is a food supplement based on carnosine and hibiscus. These two ingredients are mixed in specific proportions to form a pH buffering system which maintains the pH of the oral cavity at the proper value which is required for the regular secretion of saliva.

Aqualief® is designed as a mucoadesive tablet that will adhere to the cheek internal side, to have a prolonged action. It is expected to gradually release the ingredients over a period of at least two hours.

Aqualief® is being tested in a clinical study on 70 subjects with grade 1-2 xerostomy enrolled at the Dental Clinic of the University of Insubria. The study is currently ongoing therefore results are not yet available.

The aim of this clinical study is to evaluate if Aqualief® can be efficacious in the increasing of the saliva production in patients suffering for xerostomia as consequence of previous RT for head and neck cancer.

To this purpose, this double blind cross over study has been designed: 100 patients will be treated for 8 days with Aqualief®/placebo and then, following a 10 days wash-out period, for further 8 days with placebo /Aqualief®.

randomized, double blind, placebo controlled, cross over study

Effects of Aqualief® in Patients With Xerostomia as Consequence of Radiotherapy for Head and Neck Cancer

Evaluate the Effects of Aqualief® Mucoadhesive Tablets (a Food Supplement Based on Carnosine and Hibiscus) in Patients Who Developed Oral Xerostomia as Consequence of Radiotherapy for Head and Neck Cancer

Change of saliva production, without mechanical stimulation.

Report from patients the facility to use and palatability of the product

Latis S.r.l.

Helsinn Healthcare SA

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Yayi He, PHD,MD

This study aims to explore the application of Surface-enhanced Raman Scatting (SERS) technology in lung cancer surgery and clarify its mechanism through multi-omics mass spectrometry platform, and then further prove the clinical transformation value of this technology.

This study intends to apply the intraoperative navigation system based on Surface-enhanced Raman Scatting (SERS) technology to detect the PH of lung tissue, and to evaluate the benign and malignant resection margins of lung tissue based on this. In order to clarify the discrimination mechanism, a multi-omics mass spectrometry platform is planned to study the internal small molecules and pathway changes. In addition, the patients were followed up for five years to explore the correlation between the prognosis of patients and the PH of lung tissues and lymph nodes, which could prove the clinical transformation value of this technology.

Application of SERS Technology Based Intraoperative Navigation System in Lung Cancer

Application of Surface-enhanced Raman Scatting (SERS) Technology Based Intraoperative Navigation System in Lung Cancer

Time from randomization to death (from any cause).

The time from surgery to recurrence or the end of follow-up was defined.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ponatinib for Chronic Myeloid Leukemia (CML) Evaluation and Ph+ Acute Lymphoblastic Leukemia (ALL)	NCT01207440	Chronic Myeloid... Ph+ Acute Lymph...	Ponatinib	18 Years -	Takeda
The Gene Expression Studies of the Role of Tumor Microenvironments in Tumor Progression	NCT00638040	Hypoxia Lactic Acidosis		18 Years - 50 Years	Duke University
The Gene Expression Studies of the Role of Tumor Microenvironments in Tumor Progression	NCT00638040	Hypoxia Lactic Acidosis		18 Years - 50 Years	Duke University
Ponatinib for Chronic Myeloid Leukemia (CML) Evaluation and Ph+ Acute Lymphoblastic Leukemia (ALL)	NCT01207440	Chronic Myeloid... Ph+ Acute Lymph...	Ponatinib	18 Years -	Takeda
Effects of Aqualief® in Patients With Xerostomia as Consequence of Radiotherapy for Head and Neck Cancer	NCT03601962	Xerostomia Asialia Hyposalivation Mouth Dryness	Aqualief Placebo	18 Years -	Helsinn Healthcare SA
Application of SERS Technology Based Intraoperative Navigation System in Lung Cancer	NCT05881057	Lung Cancer		19 Years - 75 Years	Shanghai Pulmonary Hospital, Shanghai, China
Effects of Aqualief® in Patients With Xerostomia as Consequence of Radiotherapy for Head and Neck Cancer	NCT03601962	Xerostomia Asialia Hyposalivation Mouth Dryness	Aqualief Placebo	18 Years -	Helsinn Healthcare SA

Spots Global Cancer Trial Database for ph

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

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