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Ponatinib Plus Reduced-intensity Chemotherapy in the First-line Treatment of Adult Patients With Ph+ ALL (Pona-CELL)

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ClinicalTrials.gov Identifier: NCT04554459
Recruitment Status : Active, not recruiting
First Posted : September 18, 2020
Last Update Posted : December 1, 2022
Sponsor:
Collaborator:
CZECRIN - Czech Clinical Research Infrastructure Network
Information provided by (Responsible Party):
Institute of Hematology and Blood Transfusion, Czech Republic

Study Description
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Brief Summary:
This is a phase II interventional trial to evaluate the efficacy of ponatinib plus reduced-intensity chemotherapy in the first-line treatment of adult patients with Ph+ acute lymphoblastic leukemia. This combination has the potential to improve the depth of molecular responses after the induction phase of treatment. Patients who achieve a complete molecular response (CMR) at week 11 will not be directed to alloSCT and will receive consolidation chemotherapy combined with ponatinib, followed by 24 months of ponatinib maintenance. The aim is to spare individuals with a low probability of relapse from overtreatment with more intensive and toxic transplant procedure.

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia, Adult Ph+ ALL Newly Diagnosed Drug: Ponatinib 15 MG Oral Tablet Phase 2

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Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Ponatinib Plus Reduced-intensity Chemotherapy in the First-line Treatment of Adult Patients With Ph-positive Acute Lymphoblastic Leukemia
Actual Study Start Date : February 16, 2021
Estimated Primary Completion Date : September 1, 2024
Estimated Study Completion Date : September 1, 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: ponatinib plus reduced-intensity chemotherapy
ponatinib plus reduced-intensity chemotherapy in first-line treatment of Adult Ph+ ALL
 Drug: Ponatinib 15 MG Oral Tablet
ponatinib plus reduced-intensity chemotherapy in first-line treatment of Adult Ph+ ALL
Other Names:
  • Iclusig
  • AP24534
  • L01XE24


Outcome Measures
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Primary Outcome Measures :
  1. Complete Molecular Response [ Time Frame: At week 11 (acceptable window + 1 wk); after completion of two induction courses and before starting of the 1st Consolidation cycle (each induction course is 23 days with continuing ponatinib treatment till the outcome assessing) ]
    Percentage of patients with Complete Molecular Response (CMR) after 2 cycles of induction therapy composed by reduced chemotherapy and ponatinib. Minimal Residual Disease (MRD) tested by quantification of BCR-ABL1 transcript using ddPCR method


Secondary Outcome Measures :
  1. CR and CRi [ Time Frame: CR and CRi at the end of the 1st Induction Course (Day 23) and at week 11 (acceptable window + 1wk) after completion of the 2nd Induction Course and before starting of the 1st Consolidation Cycle ]
    Complete Remission (CR) and Complete Remission with incomplete blood count recovery(CRi)

  2. PFS [ Time Frame: Time from the day of CR/CRi documentation until the date of relapse, or death from any cause whichever came first, assessed up to 36 months ]
    Progression Free Survival (PFS)

  3. OS [ Time Frame: Time from the day 1 (starting of the 1st Induction Course) until the date of death from any cause, assessed up to 36 months ]
    Overall Survival (OS)

  4. AlloSCT in the first complete remission [ Time Frame: At week 11 (acceptable window + 1 wk); after completion of two induction courses and before starting of the 1st Consolidation cycle (each induction course is 23 days with continuing ponatinib treatment till the outcome assessing) ]
    Percentage of patients with suboptimal molecular response after completion of 2 induction course containing ponatinib

  5. Severity and occurence of adverse events related to ponatinib [ Time Frame: During the ponatinib treatment up to 30 days after end of treatment ]
    Severity and occurence of adverse events related to ponatinib treatment


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with newly diagnosed, previously untreated, Ph-positive [either t(9;22) and/or BCR-ABL positive] B-precursor acute lymphoblastic leukemia;
  • Age more than 18 years;
  • Eligible to intensive chemotherapy, due to general health status;
  • ECOG (Eastern Cooperative Oncology Group) performance status ≤2;
  • Absence of significant liver disease, as defined by the following criteria: total serum bilirubin ≤1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome, alanine aminotransferase (ALT) ≤2.5 × ULN or ≤5 x ULN if leukemic involvement of the liver is present, and aspartate aminotransferase (AST) ≤2.5 × ULN or ≤5 x ULN if leukemic involvement of the liver is present;
  • Adequate pancreatic function as defined by serum amylase and lipase ≤1.5 × ULN;
  • Diagnostic sample of bone marrow (or peripheral blood with >50% of blasts) available for central MRD assessment;
  • Subject has provided written informed consent prior to any screening procedure.

Exclusion Criteria:

  • Lymphoid blast crisis of chronic myelocytic leukemia (CML);
  • Active serious infection not controlled by oral or intravenous antibiotics;
  • Active known hepatitis B virus (HBV) or hepatitis C virus (HCV) or positive HIV serology;
  • History of acute pancreatitis within 1 year of study or history of chronic pancreatitis;
  • Uncontrolled hypertriglyceridemia (triglycerides > 5.1 µmol/L);
  • Clinically significant, uncontrolled or active cardiovascular disease, specifically including, but not restricted to: any history of myocardial infarction, stroke, or revascularization; unstable angina or transient ischemic attack within 6 months prior to enrolment; congestive heart failure within 6 months prior to enrolment or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards; history of clinically significant (as determined by the treating physician) atrial arrhythmia; any history of ventricular arrhythmia; any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism;
  • Uncontrolled hypertension (diastolic blood pressure >90 mmHg; systolic >140 mmHg). Patients with hypertension should be under treatment on study entry to effect blood pressure control;
  • Creatinine levels > 160 µmol/L or estimated creatinine clearance of < 50 mL/min;
  • GI disease and/or major GI surgery that may significantly alter the absorption of study drug
  • Hypersensitivity to the active substance or to any of the excipients, especially galactose intolerance.
  • Taking any medications or herbal supplements that are known to be strong inhibitors of CYP3A4 within at least 14 days before the first dose of ponatinib;
  • Female patients who are pregnant or breast feeding or patients of childbearing potential not willing to use a highly effective method of contraception during the study and for 3 months following the last dose of study drug;
  • Male patients whose sexual partner(s) are women of childbearing potential who are not willing to use a highly effective method of contraception, one of which includes a condom, during the study;
  • Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention;
  • Any concurrent severe and/or uncontrolled medical condition, which could, in the opinion of the investigator, compromise participation in the study;
  • Concurrent participation in another clinical study with an investigational medical product.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04554459


Locations
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Czechia
University Hospital Brno, Internal hematology and oncology clinic
Brno, Czechia, 60200
University Hospital Hradec Kralove, The 4th Department of Internal Medicine - Hematology
Hradec Králové, Czechia, 50005
University Hospital Olomouc, Hematooncology Clinic
Olomouc, Czechia
University Hospital Ostrava, Hematooncology Clinic
Ostrava, Czechia, 70852
University Hospital Plzen, Hematology and Oncology Department
Plzeň-Lochotín, Czechia, 304 60
University Hospital Kralovske Vinohrady, Internal Hematology Clinic
Praha, Czechia, 10034
Institute of Hematology and Blood Transfusion
Praha, Czechia, 128 00
Sponsors and Collaborators
Institute of Hematology and Blood Transfusion, Czech Republic
CZECRIN - Czech Clinical Research Infrastructure Network
Investigators
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Principal Investigator: Cyril Salek, MD Institute of Hematology and Blood Transfusion, Czech Republic
More Information
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Additional Information:

Publications of Results:

Other Publications:

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Responsible Party: Institute of Hematology and Blood Transfusion, Czech Republic
ClinicalTrials.gov Identifier: NCT04554459    
Other Study ID Numbers: Pona-CELL
First Posted: September 18, 2020    Key Record Dates
Last Update Posted: December 1, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
 Immunoproliferative Disorders
Immune System Diseases
Ponatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action