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

Neoplasm, Residual

Neoplastic Processes

Anti-Infective Agents

Inotuzumab Ozogamicin

Antineoplastic Agents, Immunological

Anti-Bacterial Agents

Antibiotics, Antitubercular

Immunotoxins

Immunoconjugates

Immunologic Factors

patients enrolled treated with the combination of Olverembatinib and Inotuzumab to clear the persistent MRD.

patients in this arm will accept a 28 days treatment regimen: Olverembatinib 40mg QOD (d1 to d28 )and Inotuzumab Ozogamicin 1.2mg/m2 (divided into 2 days, d1 and d8, 0.6mg/m2, respectively).

the usage of Olverembatinib combined with Inotuzumab Ozogamicin

Hematopoietic stem cell transplantation (HSCT) is the effective and even the only cure treatment option for ph+ acute lymphocyte leukemia (ph+ALL). However, the outcome has been insufficient and relapse remains the major cause of treatment failure and poor survival, especially for patients with persistent minimal residual disease (MRD). It is believed that clearance of MRD pre-HSCT could significantly reduce the incidence of relapse post-HSCT. Olverembatinib has been documented as a promising third generation of TKIs. Meanwhile, Inotuzumab ozogamicin (InO) , an antibody-drug conjugate approved in the US and the European Union, has been applied in relapsed/refractory acute lymphoblastic leukemia (R/R ALL) and achieved good treatment outcome. This prospective, single arm and multicenter study is to investigate the efficacy and safety of combination of Olverembatinib and Ino for MRD clearance before bridging to HSCT.

A Study of Olverembatinib Combined With Inotuzumab Ozogamicin in the Treatment ph+ ALL With MRD Persistent Positive

A Prospective, Single-arm, Multi-center Study of Olverembatinib Combined With Inotuzumab Ozogamicin in the Treatment ph+ ALL With MRD Persistent Positive

The ratio of patients achieved MRD remission. The MRD remission was defined as the fusion gene BCR-ABL quantification in bone marrow samples was lower than the detection limit of RT-PCR ( \< 0.01 %, the residual number of leukemia cells detected in our hospital was 0.0032 % ) ; at the same time, flow cytometry ( FACS ) was used to monitor the MRD of the cells, and the proportion of abnormal cells \< 0.1 % was MRD-

For patients achived MRD remission, HSCT will be performed. The one year overall survival after HSCT will be the seconday outcom.

For patients achived MRD remission, HSCT will be performed. The one year relaspe free survival after HSCT will be the seconday outcom.

For patients achived MRD remission, HSCT will be performed. The one year non-relaspe mortality after HSCT will be the seconday outcom.

Institute of Hematology & Blood Diseases Hospital, China

Translocation, Genetic

Chromosome Aberrations

Imatinib Mesylate

Novartis Pharmaceuticals

The objective of this study is to determine the efficacy and safety of imatinib mesylate in patients diagnosed as having Philadelphia chromosome positive acute lymphocytic leukemia (ALL).

Efficacy Study of Imatinib Mesylate to Treat Philadelphia-Positive Acute Lymphocytic Leukemia

Phase II Study of Imatinib Mesylate for Philadelphia-Positive Acute Lymphocytic Leukemia

Blast Crisis

Cell Transformation, Neoplastic

Carcinogenesis

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
Ponatinib for Chronic Myeloid Leukemia (CML) Evaluation and Ph+ Acute Lymphoblastic Leukemia (ALL)	NCT01207440	Chronic Myeloid... Ph+ Acute Lymph...	Ponatinib	18 Years -	Takeda
A Study of Olverembatinib Combined With Inotuzumab Ozogamicin in the Treatment ph+ ALL With MRD Persistent Positive	NCT05603156	Ph+ ALL Bone Marrow Tra... Minimal Residua...	the usage of Ol...	18 Years -	Institute of Hematology & Blood Diseases Hospital, China
Efficacy Study of Imatinib Mesylate to Treat Philadelphia-Positive Acute Lymphocytic Leukemia	NCT00154349	Philadelphia Ch...	Imatinib Mesyla...	15 Years -	Novartis
Efficacy Study of Imatinib Mesylate to Treat Philadelphia-Positive Acute Lymphocytic Leukemia	NCT00154349	Philadelphia Ch...	Imatinib Mesyla...	15 Years -	Novartis
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 Chronic Myeloid Leukemia (CML) Evaluation and Ph+ Acute Lymphoblastic Leukemia (ALL)	NCT01207440	Chronic Myeloid... Ph+ Acute Lymph...	Ponatinib	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

Spots Global Cancer Trial Database for ph+all

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

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