Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04475731
Other study ID # ALL2620
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date May 4, 2021
Est. completion date November 2024

Study information

Verified date February 2024
Source Gruppo Italiano Malattie EMatologiche dell'Adulto
Contact Paola Fazi
Phone 0670390528
Email p.fazi@gimema.it
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

This is a phase II interventional multicenter study for adult patients with Ph+ALL who: - Are MRD+ (i.e. BCR-ABL1/ABL1 >0.01) (or loose their molecular response) after whichever kind of previous treatment. MRD positivity is indeed regarded as a relapse/resistance, since it represents the early recognition of cases who will eventually experience an hematologic recurrence of disease. - Are in hematologic relapse after whichever kind of previous treatment. - Have never achieved an hematologic remission at least after one month of treatment. Patients will be treated with Ponatinib at a dose of 45 mg/die per os for 28 days for 3 cycles and - if in hematologic and extra-hematologic relapse/refractoriness, clinically fit and according to medical decision - with concurrent systemic chemotherapy. In case of CMR achievement, dosing will be reduced to 30 mg. In case of toxicity, Ponatinib will be reduced to 30 (or 15) mg daily.


Recruitment information / eligibility

Status Recruiting
Enrollment 67
Est. completion date November 2024
Est. primary completion date November 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. 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. 2. Age =18 years old with no upper age limit. 3. 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. 4. Adequate pancreatic function as defined by the following criterion: - serum lipase and amylase =1.5 × ULN. 5. For females of childbearing potential, a negative pregnancy test must be documented prior to enrollment. 6. 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. 7. Signed written informed consent according to ICH/EU/GCP and national local laws. Exclusion Criteria: 1. WHO performance status = 50% (Karnofsky) or = 3 (ECOG). 2. Uncontrolled active HBV or HCV hepatitis, or AST/ALT = 2.5 x ULN and bilirubine = 1.5 x ULN not due to the disease. 3. History of acute pancreatitis within 1 year of study or history of chronic pancreatitis. 4. History of alcohol abuse. 5. Ongoing or active uncontrolled infections. 6. Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL). 7. 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. 8. Taking medications that are known to be associated with Torsades de Pointes. 9. 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. 10. Creatinine level >2.5mg/dl or glomerular filtration rate (GFR) <20 ml/min or proteinuria >3.5 g/day. 11. Patients who are currently receiving treatment with any of the medications listed in Appendix E if the medications cannot be either discontinued or switched to a different medication prior to starting study drug. The medications listed in Appendix E have the potential to prolong QT.

Study Design


Related Conditions & MeSH terms


Intervention

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

Locations

Country Name City State
Italy Aou Ospedali Riuniti "Umberto I - G.M. Lancisi - G. Salesi"- Ancona - Sod Clinica Ematologica Ancona
Italy 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 Ao Di Rilievo Nazionale E Di Alta Specialità "San Giuseppe Moscati" - Avellino - Uoc Ematologia Con Unità Di Trapianto Avellino
Italy Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto Bari
Italy Asst Papa Giovanni Xxiii - Ospedale Di Bergamo - Sc Ematologia Bergamo
Italy Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia Bologna
Italy Asst Degli Spedali Civili Di Brescia - Uo Ematologia Brescia
Italy Aso S. Croce E Carle - Cuneo - Sc Ematologia Cuneo
Italy Aou Careggi - Firenze - Sod Ematologia Firenze
Italy Aou Policlinico "G. Martino" - Messina - Uoc Ematologia Messina
Italy Aulss 3 Serenissima, Ospedale Dell'Angelo - Mestre - Uo Ematologia Mestre
Italy Asst Grande Ospedale Metropolitano Niguarda - Milano - Sc Ematologia Milano
Italy Irccs Ospedale S. Raffaele - Milano - Uo Oncoematologia Milano
Italy Aou Federico Ii - Napoli - Uoc Ematologia Napoli
Italy Ao Di Perugia, Ospedale S. Maria Della Misericordia - Ematologia E Trapianto Midollo Osseo Perugia
Italy Ao Ospedali Riuniti Marche Nord - Ospedale San Salvatore - Pesaro - Uoc Ematologia E Centro Trapianti Pesaro
Italy Università Degli Studi Di Roma "Sapienza" - Dipartimento Di Medicina Traslazionale E Di Precisione - U.O.C. Ematologia Roma
Italy Aou "San Giovanni Di Dio E Ruggi D'Aragona" - Salerno - Uoc Ematologia E Trapianti Di Cellule Staminali Emopoietiche Salerno
Italy Ente Ecclesiastico Casa Sollievo Della Sofferenza - San Giovanni Rotondo - Ematologia San Giovanni Rotondo
Italy Aou Senese - Uoc Ematologia E Trapianti Siena
Italy Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2 Torino
Italy Aou Integrata Di Verona, Policlinico G.B. Rossi - Uoc Ematologia Verona

Sponsors (1)

Lead Sponsor Collaborator
Gruppo Italiano Malattie EMatologiche dell'Adulto

Country where clinical trial is conducted

Italy, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Duration of CMR Duration of the CMR status after 3 months of ponatinib treatment at 24 months
Secondary Hematologic remission rate The achievement of an hematologic remission in patients treated for an hematologic and extra-hematoloigc relapse and for a refractory disease. at 24 months
Secondary Best molecular response Best molecular response achieved during the follow-up at 24 months
Secondary Rate of AE/SAEs Safety profile in terms of incidence of grade >3 CTC-NCI side effects and toxicities (AE/SAEs). at 24 months
Secondary Mutational analysis Mutational analysis in terms of occurrence, type and number of BCR-ABL1 kinase domain mutations. at 24 months
Secondary Correlation between biological and MRD parameters Correlation between the achievement and duration of CMR (or MRD reduction) with the type of fusion protein (e.g. p190 or p210) and the potential occurrence of mutations, as well as with additional genomic lesions. at 24 months
Secondary Disease free survival Time interval between the achievement of CHR after three months of ponatinib and hematologic relapse of the disease or death in CHR; patients still alive, in CHR. 24 months
Secondary Overall survival Time interval between treatment start and death for any cause. 24 months
Secondary Cumulative incidence of relapse Time interval between achievement of CHR after three months of ponatinib until the date of first hematologic relapse of the disease. 24 months
Secondary Role of hematological profile on survival outcome Identification of hematological profile on survival outcome at 24 months
See also
  Status Clinical Trial Phase
Recruiting NCT05066958 - Ex-vivo Primed Memory Donor Lymphocyte Infusion to Boost Anti-viral Immunity After T-cell Depleted HSCT Phase 1/Phase 2
Completed NCT04224571 - CCCG Relapsed Acute Lymphoblastic Leukemia 2017 Study in Children Phase 2
Recruiting NCT04888442 - Phase I Study of pCAR-19B in the Treatment of Adult CD19-positive Relapsed/Refractory B-ALL Phase 1
Recruiting NCT05809284 - Determining the Mechanisms of Loss of CAR T Cell Persistence
Recruiting NCT04049383 - CAR-20/19-T Cells in Patients With Relapsed/Refractory B Cell ALL Phase 1
Not yet recruiting NCT05745714 - HEM-iSMART-C: Ruxolitinib + Venetoclax + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients With Relapsed or Refractory Hematological Malignancies Phase 1/Phase 2
Withdrawn NCT05740449 - HEM-iSMART-A: Decitabine / Venetoclax and Navitoclax in Pediatric Patients With Relapsed or Refractory Hematological Malignancies Phase 1/Phase 2
Not yet recruiting NCT06213636 - Fourth-gen CAR T Cells Targeting CD19/CD22 for Highly Resistant B-cell Lymphoma/Leukemia (PMBCL/CNS-BCL). Phase 1/Phase 2
Recruiting NCT04603872 - CAR-T Cells Combined With Dasatinib for Patients With Relapsed and/or Refractory B-cell Hematological Malignancies Early Phase 1
Recruiting NCT06445803 - CD19/CD22 CAR-T Cells in Adults With R/R ALL or NHL Phase 1
Recruiting NCT03957915 - Study of Escalating Doses of INA03 Administered Intravenously as Single Agent in Adult Patients With Relapse/Refractory Acute Leukemia Early Phase 1
Terminated NCT03705507 - International Trial of Selumetinib in Combination With Dexamethasone for the Treatment of Acute Lymphoblastic Leukaemia Phase 1/Phase 2
Recruiting NCT04340167 - Study of Anti-CD22 CAR-T Cells Treating Leukemia Children Phase 2
Recruiting NCT04325841 - Phase II Study of Anti-CD19 CAR-T Cells Treating Leukemia Children Phase 2
Recruiting NCT04605666 - CD19-CAR-T2 Cells for CD19 Positive Acute Lymphoblastic Leukemia Phase 2
Active, not recruiting NCT04340154 - Study of Sequential CAR-T Cell Treating Leukemia Children Phase 2
Recruiting NCT05292664 - Venetoclax Basket Trial for High Risk Hematologic Malignancies Phase 1
Recruiting NCT06316427 - Autologous and Donor-derived CD7 CAR-T Therapy in Refractory or Relapsed T-cell Acute Lymphoblastic Leukemia/Lymphoma Phase 1/Phase 2
Recruiting NCT05310591 - Combination of an Anti-PD1 Antibody With Tisagenlecleucel Reinfusion in Children, Adolescents and Young Adults With Acute Lymphoblastic Leukemia After Loss of Persistence Phase 1/Phase 2
Not yet recruiting NCT05705570 - A Phase I Clinical Trial Using Genetically Engineered Autologous T Cells to Express Chimeric Antigen Receptor (CAR) for Treatment of Patients With Refractory or Relapsed CD19-positive B Lymphoid Malignancies Phase 1