De Novo Philadelphia Chromosome Positive (Ph+) Acute Lymphoblastic Leukemia (ALL) MedDRA version: 14.1 Level: LLT Classification code 10000844 Term: Acute lymphoblastic leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: SPRYCEL*60x1CPR RIV 70MG
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: DASATINIB MONOHYDRATE
CAS Number: 863127-77-9
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
G.I.M.E.M.A. GRUPPO ITALIANO MALATTIE EMATOLOGICHE DELL'ADULTO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients with de novo Ph+ and/or BCR/ABL+ ALL. Age 18 years old o = 2. No evidence of central nervous system (CNS) leukemia. Normal serum level of potassium, total calcium corrected for serum albumin magnesium and phosphorus, or correctable with supplements. ALT and AST =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Impaired cardiac function, including any one of the following: LVEF 1mm in 2 or more leads and/or T wave inversions in 2 or more contiguous leads Congenital long QT syndrome. History of or presence of significant ventricular or atrial arrhythmia. Clinically significant resting bradycardia (450 msec on screening ECG (using the QTcF formula). Right bundle branch block plus left anterior hemiblock, bifascicular block. Myocardial infarction within 3 months prior to starting Dasatinib. Angina pectoris. Other clinically significant heart disease (e.g., congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen). Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of Dasatinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). Use of therapeutic warfarin. Acute or chronic liver or renal disease considered unrelated to leukemia. Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol. Active uncontrolled systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment). Treatment with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GMCSF) 1 week prior to starting study drug. Patients who are currently receiving treatment with any of the medications listed in “Appendix H” of the Protocol and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. The medications listed in “Appendix H” of the protocol have the potential to prolong the QT interval. Patients who have received any antileukemic agents and treatments including steroids for more than 14 days including 7 days pretreatment that is part of the protocol. Patients who have received any investigational drug in the last 2 weeks. Patients who have undergone major surgery 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy. Patients who are pregnant or adults of reproductive potential not employing an effective method of birth control. Women of childbearing potential must have a negative serum pregnancy test within 48 hrs prior to administration of Dasatinib. Post-menopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory). Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention. Non compliant to oral medication patients. Significant pleural effusion on baseline chest X-Ray (CXR) or pericardial effusion on baseline echocardiogram. Use of H2 blockers or proton pump inhibitors.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the trial is to estimate the feasibility of a total therapy strategy in de novo adult Ph+ ALL.;Secondary Objective: ? Treatment toxicity; ? The best molecular response obtained during Dasatinib treatment within day +85, whenever achieved from the start of the Dasatinib; ? The achievement of PCR negativity after Dasatinib induction ? The persistency of PCR negativity on maintenance treatment with Dasatinib in patients who achieved PCR negativity during the 85 days induction; ? The best molecular response obtained following Clofarabine-Cyclophosphamide treatment, or allogeneic transplant as consolidation therapy; ? The feasibility of a maintenance program with Dasatinib after consolidation with Clofarabine-Cyclophosphamide or allogeneic transplant; ? Disease-free survival (DFS); ? Cumulative incidence of relapse (CIR); ? Overall survival (OS).;Primary end point(s): The primary endpoint is the rate of patients alive in CHR who have completed the trial treatment according to the therapeutic strategy; in detail: percentage of patients PCR negative at the end of the induction treatment, alive in CHR who have completed six months of maintenance with Dasatinib; percentage of patients PCR positive at the end of the induction treatment, with an allogeneic transplant planned, alive in CHR and who have been transplanted within six months from the end of induction; percentage of patients PCR positive at the end of induction treatment, with chemotherapy planned, alive in CHR and who have received two cycles of chemotherapy within four months since the end of induction.;Timepoint(s) of evaluation of this end point: At the end of the treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? The incidence of grade >2 CTC-NCI side effects and toxicities. ? The median value of the minimum of PCR levels achieved in each patient during the Dasatinib treatment within day +85, whenever achieved from the start of the Dasatinib. ? The rate of patients who become PCR negative after Dasatinib induction. ? Out of patients who become PCR negative after induction, the rate of patients who remain persistently negative during maintenance treatment with Dasatinib (without chemotherapy or allogeneic transplant). ? The median value of the minimum of PCR levels achieved in each patient after an allogeneic transplant or Clofarabine-Cyclophosphamide treatment as consolidation therapy. ? The rate of patients alive in CHR who have completed the maintenance program with Dasatinib after an allogeneic transplant or two cycles of Clofarabine-Cyclophosphamide as consolidation therapy. ? Disease free survival estimation starting from the date of evaluation of CHR. ? Cumulative incidence of relapse estimation starting from the date of evaluation of CHR. ? Overall survival estimation starting from date of inclusion.;Timepoint(s) of evaluation of this end point: During and at the end of the treatment | — |
Countries
Italy
Contacts
Public ContactCentro Dati
GIMEMA
Outcome results
None listed