Ponatinib in Adult Ph+ ALL Patients With MRD Positivity or Hematological Relapse

NCT04475731 | Active Not Recruiting Phase 2

• 1 other identifier: ALL2620
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 22

Brief Summary

This is a phase II interventional trial to evaluate if the use of ponatinib, with or without chemotherapy, can induce a molecular remission in MRD-positive patients, in patients in hematologic and extra-hematologic relapse and in the few patients who never achieved an hematologic remission after whatever prior treatment.

Conditions

Philadelphia-Positive ALL; Acute Lymphoblastic Leukemia, in Relapse

Outcome Measures

Primary Outcomes (1)

• MRD negativity/reduction rate

  Rate of patients who achieve a MRD negativity/MRD reduction following treatment with either Ponatinib alone or in combination with systemic chemotherapy

  After 3 months of treatment

Secondary Outcomes (10)

• Duration of CMR

  at 24 months

• Hematologic remission rate

  at 24 months

• Best molecular response

  at 24 months

• Rate of AE/SAEs

  at 24 months

• Mutational analysis

  at 24 months

Study Arms (1)

Experimental arm

EXPERIMENTAL

MRD+ Ph+ ALL adult patients will receive Ponatinib x 4 weeks x 3 courses; +/-Concomitant chemotherapy (according to hematologic status). Patients will receive the study drug until disease relapse or progression.

Drug: Ponatinib

Interventions

Ponatinib DRUG

Ponatinib 45 mg/day x 4 weeks x 3 courses. +/- chemotherapy: * vincristine or * L-VAMP (leucovorin, vincristine, aracytin, methotrexate, prednisone)

Experimental arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ph+ ALL patients with evidence of MRD disease or in hematologic and extra-hematologic relapse/refractoriness after any previous treatment, will be considered eligible to enter the study.
• Age ≥18 years old with no upper age limit.
• Adequate hepatic function 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
• aspartate aminotransferase (AST) ≤2.5 × ULN.
• Adequate pancreatic function as defined by the following criterion:
• \- serum lipase and amylase ≤1.5 × ULN.
• For females of childbearing potential, a negative pregnancy test must be documented prior to enrollment.
• Female and male patients who are fertile must agree to use an effective form of contraception with their sexual partners from enrollment through 4 months after the end of treatment.
• Signed written informed consent according to ICH/EU/GCP and national local laws.

You may not qualify if:

• WHO performance status ≤ 50% (Karnofsky) or ≥ 3 (ECOG).
• Uncontrolled active HBV or HCV hepatitis, or AST/ALT ≥ 2.5 x ULN and bilirubine ≥ 1.5 x ULN not due to the disease.
• History of acute pancreatitis within 1 year of study or history of chronic pancreatitis.
• History of alcohol abuse.
• Ongoing or active uncontrolled infections.
• Uncontrolled hypertriglyceridemia (triglycerides \>450 mg/dL).
• 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 enrollment
• congestive heart failure within 6 months prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards within 6 months prior to enrollment
• 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 mm Hg; systolic \>140 mm Hg). Patients with hypertension should be under treatment on study entry to effect blood pressure control.
• Taking medications that are known to be associated with Torsades de Pointes.

Sponsors & Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto: lead

Study Sites (22)

Aou Ospedali Riuniti "Umberto I - G.M. Lancisi - G. Salesi"- Ancona - Sod Clinica Ematologica

Ancona, Italy

Location

Area Vasta N. 5 Ascoli Piceno - S. Benedetto Del Tronto, Presidio Ospedaliero Av5 Osp. Gen. Prov.Le "C.G.Mazzoni" - Uoc Ematologia

Ascoli Piceno, Italy

Location

Ao Di Rilievo Nazionale E Di Alta Specialità "San Giuseppe Moscati" - Avellino - Uoc Ematologia Con Unità Di Trapianto

Avellino, Italy

Location

Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto

Bari, Italy

Location

Asst Papa Giovanni Xxiii - Ospedale Di Bergamo - Sc Ematologia

Bergamo, Italy

Location

Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia

Bologna, Italy

Location

Asst Degli Spedali Civili Di Brescia - Uo Ematologia

Brescia, Italy

Location

Aso S. Croce E Carle - Cuneo - Sc Ematologia

Cuneo, Italy

Location

Aou Careggi - Firenze - Sod Ematologia

Florence, Italy

Location

Aou Policlinico "G. Martino" - Messina - Uoc Ematologia

Messina, Italy

Location

Aulss 3 Serenissima, Ospedale Dell'Angelo - Mestre - Uo Ematologia

Mestre, Italy

Location

Asst Grande Ospedale Metropolitano Niguarda - Milano - Sc Ematologia

Milan, Italy

Location

Irccs Ospedale S. Raffaele - Milano - Uo Oncoematologia

Milan, Italy

Location

Aou Federico Ii - Napoli - Uoc Ematologia

Napoli, Italy

Location

Ao Di Perugia, Ospedale S. Maria Della Misericordia - Ematologia E Trapianto Midollo Osseo

Perugia, Italy

Location

Ao Ospedali Riuniti Marche Nord - Ospedale San Salvatore - Pesaro - Uoc Ematologia E Centro Trapianti

Pesaro, Italy

Location

Università Degli Studi Di Roma "Sapienza" - Dipartimento Di Medicina Traslazionale E Di Precisione - U.O.C. Ematologia

Roma, Italy

Location

Aou "San Giovanni Di Dio E Ruggi D'Aragona" - Salerno - Uoc Ematologia E Trapianti Di Cellule Staminali Emopoietiche

Salerno, Italy

Location

Ente Ecclesiastico Casa Sollievo Della Sofferenza - San Giovanni Rotondo - Ematologia

San Giovanni Rotondo, Italy

Location

Aou Senese - Uoc Ematologia E Trapianti

Siena, Italy

Location

Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2

Torino, Italy

Location

Aou Integrata Di Verona, Policlinico G.B. Rossi - Uoc Ematologia

Verona, Italy

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

ponatinib

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2020
• First Posted: July 17, 2020
• Study Start: May 4, 2021
• Primary Completion: November 1, 2024
• Study Completion: November 1, 2024
• Last Updated: October 22, 2024

Record last verified: 2024-10

Locations

IT (22)