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

patients with Chronic Myeloid Leukemia - Chronic Phase (CML-CP) who initiated 3L for CML-CP

Novartis Pharmaceuticals

The study was a retrospective, non-interventional patient chart review and used a panel of oncologists/hematologists from the US to collect real-world clinical outcomes of patients with CML-CP in 3L+ and those with the T315I mutation.

This study included two distinct cohorts of CML-CP patients; that is, patients with CML-CP who initiated 3L for CML-CP (i.e., 3L cohort) and patients with CML-CP with T315I mutation (i.e., T315I cohort).

Study design for the analyses of the 3L cohort:

* The index date: date of initiation of 3L therapy for CML-CP
* The study period: period of ≥ 24 months following the index date unless the patient died before
* Patient characteristics were measured at CML diagnosis and at the index date
* The clinical outcomes of interest were measured during the study period

Study design for the analyses of the T315I cohort:

* The index date: date of initiation of a line of therapy identified as the T315I line of interest (i.e., identification of T315I mutation before initiation or over the course of line of therapy)
* The study period: period of ≥ 24 months following the index date unless the patient died before
* Patient characteristics were measured at CML diagnosis and at the index date.
* The clinical outcomes of interest were measured during the study period

Clinical Outcomes of 3L+ Therapies Among Patients With Chronic Myeloid Leukemia and Those With T315I Mutation

Assessing Real-world Clinical Outcomes of 3L+ Therapies Among Patients With Chronic Myeloid Leukemia and Those With T315I Mutation in the United States (ARC Study)

To evaluate treatment patterns in patients with CML-CP who were previously treated with TKI or other CML treatments and were relapsed/refractory to/were intolerant/had other reasons for switching of CML therapy

To evaluate the effectiveness of TKIs and other CML treatments used in 3L+ settings in patients with CML-CP

To evaluate the effectiveness of TKIs and other treatments used in a line of therapy identified as the T315I line of interest in patients with CML-CP

To evaluate treatment patterns in patients with CML-CP with T315I mutation

To evaluate real-world BCR-ABL testing frequency per the latest National Comprehensive Cancer Network (NCCN) guidelines in 3L settings in patients with CML-CP

To evaluate real-world BCR-ABL testing frequency per the latest NCCN guidelines in patients with CML-CP with T315I mutation

Leukemia, Myeloid, Accelerated Phase

40 mg tablet, taken orally once every other day

HQP1351

Xiaojun Huang, Professor

Qian Jiang, Professor

The purpose of this study is to evaluate the efficacy of HQP1351 in patients with chronic myeloid leukemia in accelerated phase (CML-AP) harboring T315I mutation. The efficacy of HQP1351 was determined by evaluating the subjects' major hematologic response (MaHR).

This is an open, single-arm, multi-center phase 2 clinical study to evaluate the efficacy and safety of oral administrated of HQP1351(40mg, QOD) in CML-AP patients with T315I mutation in China. A total of 20 CML-AP patients will be included in this pivotal study. After screening, eligible subjects will receive oral HQP1351 40mg on a continues once every other day dosing regimen, until disease progression, drug intolerance, or meet other treatment conditions to discontinue the study. During the course of treatment, each subject will be assessed regularly for hematological, cytogenetic and molecular responses. At the same time, safety information also will be evaluated.

A Pivotal Study of HQP1351 in Patients of Chronic Myeloid Leukemia in Accelerated Phase With T315I Mutation

A Phase II Multi-center, Open Label Study of HQP1351 in Chinese Patients of Chronic Myeloid Leukemia With T315I Mutation in Accelerated Phase

During the course of HQP1351 therapy, the relationship between BCR-ABL1 kinase region/other mutations and drug resistance/disease progression will be measured.

Objects' quality of life will be measured during the course of HQP1351 therapy by European Organization for Research and Treatment (EORTC) quality of life questionnaire core-30 version3 \[QLQ-C30(V3) questionnaire\].

MaHR is the proportion of patients achieving Complete hematologic response (CHR) or no evidence of leukemia (NEL). It is defined as the best response obtained by the subjects during the whole treatment process of the study.

CHR is the proportion of patients achieving CHR after being treated with HQP1351. It is defined as the best response obtained by the subjects during the whole treatment process of the study.

MCyR is the proportion of patients achieving Complete cytogenetic response (CCyR: defined as 0% Philadelphia chromosome-positive \[Ph+\] metaphases by cytogenetic analysis of bone marrow) or Partial Cytogenetic Response (PCyR: defined as \>0% to 35% Ph+ metaphases by cytogenetic analysis of bone marrow). It is defined as the best response obtained by the subjects during the whole treatment process of the study.

CCyR is the proportion of patients achieving CCyR after being treated with HQP1351. It is defined as the best response obtained by the subjects during the whole treatment process of the study.

MMR is the proportion of patients achieving a ratio of ≤0.1% breakpoint cluster region (BCR) abelson leukemia (ABL) to ABL transcripts on the international scale (≤0.1% BCR-ABL/ABL\[IS\]) after being treated with HQP1351. It is defined as the best response obtained by the subjects during the whole treatment process of the study.

The time to response is defined as the interval between the first use of HQP1351 and the first date at which the criteria for response are met. The subject who isn't met the response criteria will be censored at the last assessment time.

Duration of response is defined as the interval between the first assessment at which the criteria for response are met until the earliest date at which the criteria for progression are met, and the subject who isn't met the progression criteria will be censored at the last assessment time. The duration of response is calculated only for subjects who achieved response.

PFS is defined as the interval between the first dose date of HQP1351 treatment and the first date at which the criteria for progression are met, or death. The subject who isn't progression or death will be censored at the last response assessment.

OS is defined as the interval between the first dose date of HQP1351 treatment and date of death, censored at the last contact date to be alive.

Patients with HQP1351 treatment related AE, SAE will be assessed according NCI CTCAE Version 5.0.

Ascentage Pharma Group Inc.

Blast Crisis

Blinatumomab

Ascentage Pharma HQP1351 bioavailable inhibitor

Administered in all patients as a continuous IV infusion at the dosage of 28μg daily (9μg daily for Cycle 1 Day 1 to Day 7).

Bill Garrett

Sarah Weaver

Omer Jamy, MD

London Hall

Thad Beck, MD

Paul Koller, MD

Shannon Gleason

Anthony Hunter, MD

Amelia Barkman

Maria Baer, MD

Erik Lewerenz

Sudipto Mukherjee, MD

Jovitta Jacob

Elias Jabbour, MD

Kaysey Orlowski

Vivian Oehler, MD

Yifan Zhai, MD, PhD

A multi-center, open-label, randomized, phase Ib study to evaluate the pharmacokinetics (PK) of HQP1351 and to determine the recommended phase 2 dose (RP2D) of HQP1351 in subjects with CML chronic phase (CP), accelerated phase (AP), or blast phase (BP) or with Ph+ ALL, who have experienced resistance or intolerance to at least two tyrosine kinase inhibitors (TKIs) or in subjects with Ph+ B-cell precursor (BCP) ALL or lymphoid blast phase CML (CML LBP), who have experienced resistance or intolerance to at least one second or later generation TKI.

Approximately 40 patients will be randomized at 3:3:2 ratio into one of three HQP1351 monotherapy dose cohorts (Cohort A, B, and C): 30 mg every other day (QOD), 40 mg QOD, and 50 mg QOD, with 15, 15, and 10 patients in Cohort A, B, and C. The first cycle of 28 days is considered as the dose-limiting toxicity (DLT) observation period. If the incidence of DLTs exceeds 20% (2 patients) in 50 mg dose cohort during the first cycle of therapy, this dose cohort will be stopped. The randomization will be stratified to 4 groups: T315I mutated CML-CP and CML-AP, T315I un-mutated CML-CP, T315I unmutated CML-AP, and CML-BP and Ph+ ALL to ensure that the subgroups are represented across all dose cohorts. Blood samples will be collected from each subject at specified time points to evaluate the PK of HQP1351. RP2D of HQP1351 will be determined based on the comprehensive analyses of the PK, safety, and efficacy data of the US patients treated with HQP1351, when compared with that in the Chinese patients.

Eligible patients will have disease resistance to or intolerance to at least two TKIs, for patients with T315I mutation, number of pretreated TKIs is not restricted. Patients will be administered HQP1351 orally QOD during a period of 28 days (1 cycle).

Cohort D (HQP1351 + blinatumomab) will enroll patients with relapsed/refractory Ph+ BCP ALL or CML-BP using a dose escalation and expansion design. Patients will be administered HQP1351 orally QOD at an assigned dose with blinatumomab at repeated 42-day cycles. The first cycle of 42 days is considered as the DLT observation period. The initial dose of HQP1351 will be 30 mg QOD.

A total of 40 patients will be randomized at 3:3:2 ratio into one of the three dose cohorts (Cohorts A, B, and C): 30 mg every other day (QOD), 40 mg QOD and 50 mg QOD, with 15, 15, and 10 patients in Cohort A, B, and C.

For Cohort D: 14 to 22 Ph+ BCP ALL or CML LBP patients will be enrolled.

Study of HQP1351 in Subjects With Refractory CML and Ph+ ALL

A Phase Ib Study of the Pharmacokinetics, Safety and Efficacy of Orally Administered HQP1351 in Subjects With Refractory Chronic Myeloid Leukemia (CML) and Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)

To evaluate the Maximum Plasma Concentration (Cmax) of HQP1351

To evaluate the Area Under the Curve (AUC) of HQP1351

Leukemia, Myeloid, Chronic-Phase

Asciminib

200 mg asciminib orally twice daily (BID)

Asciminib will be supplied as 20 mg or 40 mg strength tablets will be administered orally in accordance with the assigned cohort.

ABL001

This study will be a multicenter Phase IIIb open-label, three-cohort study of asciminib in patients with CML-CP without T315I mutation who have had at least 2 prior TKIs and CML-CP harboring the T315I mutation with at least 1 prior TKI

This trial consists of three periods: screening and baseline for up to 21 days, active treatment for up to 72 weeks and a safety follow up period for 30 days.

One hundred and fifteen (115) patients with chronic myeloid leukemia in chronic phase (CML-CP) without T315I mutation who have had at least 2 prior Tyrosine Kinase Inhibitors (TKIs) and CML-CP with the T315I mutation with at least 1 prior TKI will be considered for the current study

Informed consent will be obtained before any procedures are performed for the study including eligibility assessments. The results of the real time quantitative polymerase chain reaction (RQ-PCR) must be available prior to randomization and first dose of study treatment.

Patients with CML-CP without T315I mutation will be randomly assigned to either cohort A or B. Patients with the T315I mutation will be enrolled in cohort C. During treatment period asciminib will be taken orally: Cohort A will be administered 40 mg twice a day, Cohort B will be administered 80 mg once a day and Cohort C will be administered 200 mg twice a day. The patients will be treated up to end of study treatment period defined as up to 72 weeks after the last patient receives the first dose. Patients may be discontinued from treatment with the study drug at any time due to unacceptable toxicity, disease progression and/or at the discretion of the investigator or the patient.

Cohort A and B will be randomized but not C

Asciminib in Monotherapy for Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and Without T315I Mutation

An Open Label, Multi-center Phase IIIb Study of Asciminib (ABL001) Monotherapy in Previously Treated Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and Without T315I Mutation

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on

https://www.clinicalstudydatarequest.com/

Adverse events (AEs) and serious adverse events (SAEs) will be summarized by cohort. Clinically significant findings for vitals, laboratory values and electrocardiogram (ECG) will be reported as adverse events and or serious adverse events as determined by the investigator.

A complete hematologic response (CHR) is defined as all of the following present for ≥ 4 weeks: white blood count (WBC) \<10 x 109/L, platelet count \<450 x 109/L, basophils \<5%, no blasts and promyelocytes in peripheral blood, myelocytes + metamyelocytes \< 5% in peripheral blood, no evidence of extramedullary disease, including spleen and liver

The rate of molecular response (MR2) by 12, 24, 48 and 72 weeks after the start of first study medication is defined as ≥ 2 log reduction of BCR-ABL (transcript from standardized baseline or ≤ 1% BCR-ABL/ABL % by international scale, measured by real-time quantitative polymerase chain reaction (RQ-PCR). BCR-ABL fusion gene is also called the Philadelphia chromosome. Rate for MMR is defined as ≥ 3 log reduction, MR4 is defined as ≥ 4 log reduction and MR4.5 is defined as ≥ 4.5 log reduction.

Time to achieving a response level is defined as the time from the date of the first dose of study medication to the first documented achievement of a each defined response level. Time to achieve a specific response level will be analyzed using the Kaplan-Meier Product-Limit method. Patients who are known to be without achieving that response level will be censored at the last adequate assessment.

Duration of Response (DOR) is the time from the date of the first documented a molecular response level to the date of first documented loss of the response level or death due to any cause, whichever occurs first. DOR for each response level will be analyzed using the Kaplan-Meier Product-Limit method. Participants continuing without that event will be censored at the date of their last adequate response assessment.

Progression Free Survival (PFS) is defined as time from the first dose of study medication to disease progression to accelerated phase/blast crisis (AP/BC) or death due to any cause, whichever occurs first. PFS will be analyzed using the Kaplan-Meier Product-Limit method

Overall Survival (OS) is defined as the time from the first dose of study medication to death due to any cause during study. If a patient is not known to have died, then OS will be censored at the latest date the patient was known to be alive. OS will be analyzed using the Kaplan-Meier Product-Limit method

Translocation, Genetic

Chromosome Aberrations

80 mg once daily at approximately the same time each day or 40 mg twice daily per Investigator's discretion at approximately 12-hour intervals

200 mg twice daily at approximately 12-hour intervals

Film-coated tablets with 40 mg dose strength taken orally

The Drugs Controller General of India (DCGI) has granted approval for Asciminib film-coated 40 mg tablets on 20 Oct 2023 with the condition to perform a Phase IV clinical study in Indian patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) per the India Prescribing Information (PI). The purpose of this prospective, multicenter, single-arm, open-label, Phase IV study is, therefore, to confirm the safety and efficacy of Asciminib in Indian patients with Ph+ CML-CP (without threonine-315 residue with isoleucine \[T315I\] mutation), previously treated with 2 or more tyrosine kinase inhibitors (TKIs) and patients with Ph+ CML-CP with T315I mutation.

This is a Phase IV, prospective, multicenter, single-arm, open-label, post-authorization interventional study to assess the safety and efficacy of asciminib in Indian participants with Ph+ CML-CP (without T315I mutation), previously treated with 2 or more TKIs and participants with Ph+ CML-CP with T315I mutation irrespective of the line of treatment.

The study will include 3 periods: a screening period (up to 21 days), a treatment period of up to 6 months with asciminib (with dosing according to mutation status), and a safety follow-up period for 30 days after the last dose of the study treatment. Completion of the safety follow-up period after the last dose of the study treatment will be considered as the End of Study (EOS).

After obtaining the written informed consent form (ICF) from the participant or their legally authorized representatives (LARs), the participants will undergo screening procedures to confirm their eligibility for the study.

The results of the breakpoint cluster region gene-Abelson proto-oncogene 1, nonreceptor tyrosine kinase gene (BCR::ABL1) real-time quantitative polymerase chain reaction (RQ-PCR) as well as the T315I mutation report need to be established and documented prior to enrollment into the study in the screening period in line with the inclusion criteria of the study. Participants with previously documented T315I mutated CML-CP will be directly considered for the screening procedures. If the status of the T315I mutation is not known, the participant will undergo a standardized Sanger sequencing/PCR/next-generation sequencing (NGS)-based T315I mutation test (as per the availability at the site).

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
Clinical Outcomes of 3L+ Therapies Among Patients With Chronic Myeloid Leukemia and Those With T315I Mutation	NCT05611216	Chronic Myeloid...		18 Years -	Novartis
A Pivotal Study of HQP1351 in Patients of Chronic Myeloid Leukemia in Accelerated Phase With T315I Mutation	NCT03883100	Chronic Myeloid...	HQP1351	18 Years -	Ascentage Pharma Group Inc.
Study of HQP1351 in Subjects With Refractory CML and Ph+ ALL	NCT04260022	Leukemia, Myelo... Myeloid Leukemi... Chronic Myeloid... Philadelphia Po... B Cell Precurso...	Ascentage Pharm... Blinatumomab	18 Years -	Ascentage Pharma Group Inc.
Ponatinib for Chronic Myeloid Leukemia (CML) Evaluation and Ph+ Acute Lymphoblastic Leukemia (ALL)	NCT01207440	Chronic Myeloid... Ph+ Acute Lymph...	Ponatinib	18 Years -	Takeda
Clinical Outcomes of 3L+ Therapies Among Patients With Chronic Myeloid Leukemia and Those With T315I Mutation	NCT05611216	Chronic Myeloid...		18 Years -	Novartis
Asciminib in Monotherapy for Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and Without T315I Mutation	NCT04666259	Chronic Myeloge...	ABL001	18 Years -	Novartis
Clinical Study of Asciminib in Previously Treated Indian Patients With Ph+ CML-CP Without T315I Mutation and in Patients With Ph+ CML-CP With T315I Mutation	NCT06427811	Philadelphia Ch...	Asciminib	18 Years -	Novartis
French Study to Highlight the Unmet Treatment Needs of 3L+ CP-CML and With T315I-mutated CML Patients	NCT05619978	Chronic Myeloid...	3L Therapy T315I	18 Years - 99 Years	Novartis
Study of HQP1351 in Subjects With Refractory CML and Ph+ ALL	NCT04260022	Leukemia, Myelo... Myeloid Leukemi... Chronic Myeloid... Philadelphia Po... B Cell Precurso...	Ascentage Pharm... Blinatumomab	18 Years -	Ascentage Pharma Group Inc.

Spots Global Cancer Trial Database for t315i mutation