search
Back to results

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

Primary Purpose

Chronic Myeloid Leukemia, Ph+ Acute Lymphoblastic Leukemia

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ponatinib
Sponsored by
Ariad Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myeloid Leukemia focused on measuring CML, ALL, PH, ponatinib, Ph+ALL, T315I mutation, Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Participants must have CML in any phase (CP, AP, or BP of any phenotype) or Ph+ ALL
  • Previously treated with and developed resistance or intolerance to dasatinib or nilotinib OR developed the T3151 mutation after any tyrosine kinase inhibitor (TKI) therapy
  • ≥18 years old
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Minimum life expectancy of ≥3 months
  • Adequate kidney function
  • Adequate liver function
  • Normal pancreatic function
  • Normal QT Fridericia-corrected interval (QTcF) ≤450 ms for males and ≤470 ms for females
  • Negative pregnancy test (if woman of childbearing potential)
  • Agree to use effective form of contraception (as applicable)
  • Ability to comply with study procedures, in the Investigator's opinion

Exclusion Criteria:

  • Received prior TKI treatment within 7 days prior to receiving the first dose of ponatinib, or have not recovered from adverse events (except alopecia) due to agents previously administered.

  • Received other therapies as follows:

    1. For CML chronic phase (CP) and accelerated phase (AP) participants, received hydroxyurea or anagrelide within 24 hours prior to receiving the first dose of ponatinib; interferon, cytarabine, or immunotherapy within 14 days prior to first dose of ponatinib; or any other cytotoxic chemotherapy, radiotherapy, or investigational therapy within 28 days prior to receiving the first dose of ponatinib.
    2. For CML blast phase (BP) participants, received chemotherapy within 14 days prior to the first dose of ponatinib.
    3. For Ph+ ALL participants, received corticosteroids within 24 hours before the first dose of ponatinib; or vincristine within 7 days prior to the first dose of ponatinib; or received other chemotherapy within 14 days prior to the first dose of ponatinib.
  • Underwent stem cell transplant <60 days prior to receiving first dose of ponatinib
  • Evidence of on-going graft versus-host disease (GVHD), or GVHD requiring immunosuppressive therapy
  • Taking medications that are known to be associated with Torsades de Pointes
  • Require concurrent treatment with immunosuppressive agents (other than corticosteroids prescribed for a short course of therapy)
  • Previously treated with ponatinib
  • CML CP participants are excluded if they are in Complete cytogenetic response (CCyR)
  • Participants with CML AP, CML BP, or Ph+ ALL are excluded if they are in Major Hematologic Response (MaHR).
  • Have active Central Nervous System (CNS) disease
  • Have significant or active cardiovascular disease
  • Have a significant bleeding disorder unrelated to CML or Ph+ALL
  • Have a history of pancreatitis or alcohol abuse
  • Have uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL)
  • Have malabsorption syndrome or other gastrointestinal illness that could affect absorption of ponatinib
  • Diagnosed with another primary malignancy in the past 3 years
  • Pregnant or lactating
  • Underwent major surgery within 14 days prior to first dose of ponatinib
  • Have ongoing or active infection
  • Suffer from any other condition or illness that would compromise safety or interfere with evaluation of the drug

Sites / Locations

  • Royal North Shore Hospital
  • Princess Alexandra Hospital
  • Royal Adelaide Hospital
  • Alfred Hospital
  • Peter MacCallum Cancer Centre
  • UCL Bruxelles
  • UZ Leuven
  • Institut Bergonie
  • Hopital Andre Mignot
  • Hopital Claude Huriez CHRU
  • Chu Brabois
  • Hopital Archet
  • Hopital St. Louis
  • Hopital Edouard Herriot
  • Entre Hospitalier Universitaire
  • Hopital de Purpan
  • Charite - Universitatsmedizin Berlin,
  • Klinikum der Goethe Universitat,
  • Universitatsklinikum Jena
  • University of Heidelberg
  • III. Med. Klinik und Poliklinik
  • Universita di Bologna
  • University of Modena
  • University of Milano Bicocca
  • University of Turin
  • University Tor Vergata
  • The Catholic University of Korea, Seoul St.Mary's Hospital
  • VU University Medical Center
  • University Medical Center Groeningen
  • Singapore General Hospital
  • Hospital Clinic
  • La Paz
  • Hospital Universitario de Salamanca
  • Hospital Clinico of Valencia
  • Lund University
  • Karolinska Hospital
  • University Hospital Uppsala
  • Gartnavel General Hospital
  • Royal Liverpool University Hospital
  • Hammersmith Hospital
  • Royal Victoria Infirmary
  • University of Nottingham

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort A: CP-CML R-I

Cohort B: CP-CML with T315I Mutation

Cohort C: Accelerated Phase (AP)-CML R-I

Cohort D: AP-CML with T315I Mutation

Cohort E: Blast Phase (BP)-CML/Ph+ ALL R-I

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

Unassigned to Cohorts A-F

Arm Description

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).

Outcomes

Primary Outcome Measures

Percentage of CP-CML Participants With Major Cytogenetic Response (MCyR)
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.
Percentage of AP-CML Participants With Major Hematologic Response (MaHR)
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.
Percentage of BP-CML/Ph+ ALL Participants With MaHR
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.

Secondary Outcome Measures

Percentage of CP-CML Participants With CHR
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).
Percentage of CP-CML Participants With Confirmed MCyR
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.
Percentage of CP-CML Participants With Major Molecular Response (MMR)
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).
Percentage of AP-CML or BP-CML/Ph+ ALL Participants With MCyR
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.
Percentage of AP-CML or BP-CML/Ph+ ALL Participants With Confirmed MCyR
Confirmed MCyR is defined as 2 assessments of CCyR or PCyR at least 28 days apart.
Percentage of AP-CML or BP-CML/Ph+ ALL Participants With MMR
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).
Time to Response
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
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.
Progression-free Survival (PFS)
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.
Overall Survival (OS)
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.
Number of Participants With Treatment-Emergent Adverse Event (TEAE) and Serious AE (SAE)
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.

Full Information

First Posted
September 20, 2010
Last Updated
January 18, 2021
Sponsor
Ariad Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT01207440
Brief Title
Ponatinib for Chronic Myeloid Leukemia (CML) Evaluation and Ph+ Acute Lymphoblastic Leukemia (ALL)
Acronym
PACE
Official Title
A Pivotal Phase 2 Trial of Ponatinib (AP24534) in Patients With Refractory Chronic Myeloid Leukemia and Ph+ Acute Lymphoblastic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
September 30, 2010 (Actual)
Primary Completion Date
December 20, 2018 (Actual)
Study Completion Date
January 17, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ariad Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myeloid Leukemia, Ph+ Acute Lymphoblastic Leukemia
Keywords
CML, ALL, PH, ponatinib, Ph+ALL, T315I mutation, Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
449 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort A: CP-CML R-I
Arm Type
Experimental
Arm Description
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).
Arm Title
Cohort B: CP-CML with T315I Mutation
Arm Type
Experimental
Arm Description
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).
Arm Title
Cohort C: Accelerated Phase (AP)-CML R-I
Arm Type
Experimental
Arm Description
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).
Arm Title
Cohort D: AP-CML with T315I Mutation
Arm Type
Experimental
Arm Description
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).
Arm Title
Cohort E: Blast Phase (BP)-CML/Ph+ ALL R-I
Arm Type
Experimental
Arm Description
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).
Arm Title
Cohort F: BP-CML or Ph+ ALL with T315I Mutation
Arm Type
Experimental
Arm Description
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).
Arm Title
Unassigned to Cohorts A-F
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Ponatinib
Other Intervention Name(s)
AP24534, Iclusig
Intervention Description
Ponatinib tablets.
Primary Outcome Measure Information:
Title
Percentage of CP-CML Participants With Major Cytogenetic Response (MCyR)
Description
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.
Time Frame
Up to 12 months after initiation of study treatment
Title
Percentage of AP-CML Participants With Major Hematologic Response (MaHR)
Description
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.
Time Frame
Up to 6 months after initiation of study treatment
Title
Percentage of BP-CML/Ph+ ALL Participants With MaHR
Description
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.
Time Frame
Up to 6 months after initiation of study treatment
Secondary Outcome Measure Information:
Title
Percentage of CP-CML Participants With CHR
Description
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).
Time Frame
Every 3 cycles up to 39 cycles, followed by every subsequent sixth cycle (Up to approximately 48 months after first dose)
Title
Percentage of CP-CML Participants With Confirmed MCyR
Description
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.
Time Frame
Every 3 cycles up to 39 cycles, followed by every subsequent sixth cycle (Up to approximately 48 months after first dose)
Title
Percentage of CP-CML Participants With Major Molecular Response (MMR)
Description
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).
Time Frame
Every 3 cycles up to 39 cycles, followed by every subsequent sixth cycle (Up to approximately 48 months after first dose)
Title
Percentage of AP-CML or BP-CML/Ph+ ALL Participants With MCyR
Description
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.
Time Frame
Every 2 cycles up to 26 cycles, followed by every 3 cycles from cycles 27 through 39, and then every subsequent sixth cycle (Up to approximately 48 months after first dose)
Title
Percentage of AP-CML or BP-CML/Ph+ ALL Participants With Confirmed MCyR
Description
Confirmed MCyR is defined as 2 assessments of CCyR or PCyR at least 28 days apart.
Time Frame
Every 2 cycles up to 26 cycles, followed by every 3 cycles from cycles 27 through 39, and then every subsequent sixth cycle (Up to approximately 48 months after first dose)
Title
Percentage of AP-CML or BP-CML/Ph+ ALL Participants With MMR
Description
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).
Time Frame
Every 2 cycles up to 26 cycles, followed by every 3 cycles from cycles 27 through 39, and then every subsequent sixth cycle (Up to approximately 48 months after first dose)
Title
Time to Response
Description
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.
Time Frame
Up to approximately 48 months after first dose
Title
Duration of Response
Description
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.
Time Frame
Up to approximately 48 months after first dose
Title
Progression-free Survival (PFS)
Description
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.
Time Frame
Every 12 weeks ± 2 weeks from last dose of study drug or the investigator/participant decision to discontinue treatment, whichever occurred later (Up to approximately 96 months after last dose)
Title
Overall Survival (OS)
Description
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.
Time Frame
From the first dose of study treatment until death (Up to 96 months post last dose)
Title
Number of Participants With Treatment-Emergent Adverse Event (TEAE) and Serious AE (SAE)
Description
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.
Time Frame
From first dose up to 30 days after last dose of the study drug (Up to approximately 49 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants must have CML in any phase (CP, AP, or BP of any phenotype) or Ph+ ALL Previously treated with and developed resistance or intolerance to dasatinib or nilotinib OR developed the T3151 mutation after any tyrosine kinase inhibitor (TKI) therapy ≥18 years old Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 Minimum life expectancy of ≥3 months Adequate kidney function Adequate liver function Normal pancreatic function Normal QT Fridericia-corrected interval (QTcF) ≤450 ms for males and ≤470 ms for females Negative pregnancy test (if woman of childbearing potential) Agree to use effective form of contraception (as applicable) Ability to comply with study procedures, in the Investigator's opinion Exclusion Criteria: Received prior TKI treatment within 7 days prior to receiving the first dose of ponatinib, or have not recovered from adverse events (except alopecia) due to agents previously administered. Received other therapies as follows: For CML chronic phase (CP) and accelerated phase (AP) participants, received hydroxyurea or anagrelide within 24 hours prior to receiving the first dose of ponatinib; interferon, cytarabine, or immunotherapy within 14 days prior to first dose of ponatinib; or any other cytotoxic chemotherapy, radiotherapy, or investigational therapy within 28 days prior to receiving the first dose of ponatinib. For CML blast phase (BP) participants, received chemotherapy within 14 days prior to the first dose of ponatinib. For Ph+ ALL participants, received corticosteroids within 24 hours before the first dose of ponatinib; or vincristine within 7 days prior to the first dose of ponatinib; or received other chemotherapy within 14 days prior to the first dose of ponatinib. Underwent stem cell transplant <60 days prior to receiving first dose of ponatinib Evidence of on-going graft versus-host disease (GVHD), or GVHD requiring immunosuppressive therapy Taking medications that are known to be associated with Torsades de Pointes Require concurrent treatment with immunosuppressive agents (other than corticosteroids prescribed for a short course of therapy) Previously treated with ponatinib CML CP participants are excluded if they are in Complete cytogenetic response (CCyR) Participants with CML AP, CML BP, or Ph+ ALL are excluded if they are in Major Hematologic Response (MaHR). Have active Central Nervous System (CNS) disease Have significant or active cardiovascular disease Have a significant bleeding disorder unrelated to CML or Ph+ALL Have a history of pancreatitis or alcohol abuse Have uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL) Have malabsorption syndrome or other gastrointestinal illness that could affect absorption of ponatinib Diagnosed with another primary malignancy in the past 3 years Pregnant or lactating Underwent major surgery within 14 days prior to first dose of ponatinib Have ongoing or active infection Suffer from any other condition or illness that would compromise safety or interfere with evaluation of the drug
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director Clinical Science
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Royal North Shore Hospital
City
St Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Facility Name
Princess Alexandra Hospital
City
Woolloongabba
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Alfred Hospital
City
Box Hill
State/Province
Victoria
ZIP/Postal Code
3128
Country
Australia
Facility Name
Peter MacCallum Cancer Centre
City
East Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
Facility Name
UCL Bruxelles
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Institut Bergonie
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Hopital Andre Mignot
City
Le Chesnay
ZIP/Postal Code
78157
Country
France
Facility Name
Hopital Claude Huriez CHRU
City
Lille
ZIP/Postal Code
59307
Country
France
Facility Name
Chu Brabois
City
Nancy
ZIP/Postal Code
54551
Country
France
Facility Name
Hopital Archet
City
Nice
ZIP/Postal Code
6202
Country
France
Facility Name
Hopital St. Louis
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
Hopital Edouard Herriot
City
Pierre-Benite
ZIP/Postal Code
69495
Country
France
Facility Name
Entre Hospitalier Universitaire
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
Hopital de Purpan
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Charite - Universitatsmedizin Berlin,
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Klinikum der Goethe Universitat,
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Universitatsklinikum Jena
City
Jena
ZIP/Postal Code
07747
Country
Germany
Facility Name
University of Heidelberg
City
Mannheim
ZIP/Postal Code
68169
Country
Germany
Facility Name
III. Med. Klinik und Poliklinik
City
Munchen
ZIP/Postal Code
81675
Country
Germany
Facility Name
Universita di Bologna
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
University of Modena
City
Modena
ZIP/Postal Code
41124
Country
Italy
Facility Name
University of Milano Bicocca
City
Monza
ZIP/Postal Code
20052
Country
Italy
Facility Name
University of Turin
City
Orbassano (TO)
ZIP/Postal Code
10043
Country
Italy
Facility Name
University Tor Vergata
City
Roma
ZIP/Postal Code
144
Country
Italy
Facility Name
The Catholic University of Korea, Seoul St.Mary's Hospital
City
Seoul
ZIP/Postal Code
137-701
Country
Korea, Republic of
Facility Name
VU University Medical Center
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
University Medical Center Groeningen
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Facility Name
Singapore General Hospital
City
Singapore
ZIP/Postal Code
169608
Country
Singapore
Facility Name
Hospital Clinic
City
Barcelona
ZIP/Postal Code
8036
Country
Spain
Facility Name
La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hospital Universitario de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Hospital Clinico of Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
Lund University
City
Lund
ZIP/Postal Code
22185
Country
Sweden
Facility Name
Karolinska Hospital
City
Stockholm
ZIP/Postal Code
17176
Country
Sweden
Facility Name
University Hospital Uppsala
City
Uppsala
ZIP/Postal Code
75185
Country
Sweden
Facility Name
Gartnavel General Hospital
City
Glasgow
ZIP/Postal Code
G12 0XB
Country
United Kingdom
Facility Name
Royal Liverpool University Hospital
City
Liverpool
ZIP/Postal Code
L7 8XP
Country
United Kingdom
Facility Name
Hammersmith Hospital
City
London
ZIP/Postal Code
W12 0NN
Country
United Kingdom
Facility Name
Royal Victoria Infirmary
City
Newcastle
ZIP/Postal Code
NE2 4HH
Country
United Kingdom
Facility Name
University of Nottingham
City
Nottingham
ZIP/Postal Code
NG5 1PB
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing Access Criteria
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Citations:
PubMed Identifier
29567798
Citation
Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre PD, Paquette R, Chuah C, Nicolini FE, Apperley JF, Khoury HJ, Talpaz M, DeAngelo DJ, Abruzzese E, Rea D, Baccarani M, Muller MC, Gambacorti-Passerini C, Lustgarten S, Rivera VM, Haluska FG, Guilhot F, Deininger MW, Hochhaus A, Hughes TP, Shah NP, Kantarjian HM. Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial. Blood. 2018 Jul 26;132(4):393-404. doi: 10.1182/blood-2016-09-739086. Epub 2018 Mar 22.
Results Reference
result
PubMed Identifier
34991679
Citation
Januzzi JL, Garasic JM, Kasner SE, McDonald V, Petrie MC, Seltzer J, Mauro M, Croce K, Berman E, Deininger M, Hochhaus A, Pinilla-Ibarz J, Nicolini F, Kim DW, DeAngelo DJ, Kantarjian H, Xu J, Hall T, Srivastava S, Naranjo D, Cortes J. Retrospective analysis of arterial occlusive events in the PACE trial by an independent adjudication committee. J Hematol Oncol. 2022 Jan 6;15(1):1. doi: 10.1186/s13045-021-01221-z. Erratum In: J Hematol Oncol. 2022 Mar 23;15(1):33.
Results Reference
derived
PubMed Identifier
24180494
Citation
Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre P, Paquette R, Chuah C, Nicolini FE, Apperley JF, Khoury HJ, Talpaz M, DiPersio J, DeAngelo DJ, Abruzzese E, Rea D, Baccarani M, Muller MC, Gambacorti-Passerini C, Wong S, Lustgarten S, Rivera VM, Clackson T, Turner CD, Haluska FG, Guilhot F, Deininger MW, Hochhaus A, Hughes T, Goldman JM, Shah NP, Kantarjian H; PACE Investigators. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med. 2013 Nov 7;369(19):1783-96. doi: 10.1056/NEJMoa1306494. Epub 2013 Nov 1.
Results Reference
derived
PubMed Identifier
22825216
Citation
O'Hare T, Zabriskie MS, Eiring AM, Deininger MW. Pushing the limits of targeted therapy in chronic myeloid leukaemia. Nat Rev Cancer. 2012 Jul 24;12(8):513-26. doi: 10.1038/nrc3317. Erratum In: Nat Rev Cancer. 2012 Dec;12(12):886.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs