De novo Philadelphia-Chromosome positive acute lymphoblastic leukemia (Ph+ALL) MedDRA version: 24.0 Level: LLT Classification code 10080018 Term: Philadelphia positive acute lymphocytic leukemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Iclusig ®
Pharmaceutical Form: Film-coated tablet
Trade Name: Blincyto
Product Name: Blinatumomab
Pharmaceutical Form: Powder and solvent for concentrate for solution for infusion
Produc
Sponsors
Goethe-University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female patients >= 18 years, LLN (lower limit of normal) of potassium and magnesium, or cor-rected to within normal limits with supplements, prior to the first dose of study medication • Serum lipase = 1.5 x ULN. For serum lipase > ULN - = 1.5 x ULN, value must be considered not clinically significant and not associated with risk factors for acute pancreatitis • Normal QTcF interval =450 ms for males and =470 ms for females • Signed and dated written informed consent is available • Participation in the registry of the German Multicenter Study Group for Adult ALL (GMALL) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 215 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: • History of malignancy other than ALL diagnosed within 5 years (yrs) prior to start of pro-tocol-specified therapy with defined exceptions: • Adequately treated non-melanoma skin cancer or lentigo maligna without evi-dence of disease • Adequately treated cervical carcinoma in situ without evidence of disease • Adequately treated breast ductal carcinoma in situ without evidence of disease • Prostatic intraepithelial neoplasia without evidence of prostate cancer • Contraindications against the use of Imatinib, Ponatinib, chemotherapy or Blinatumomab • Patient previously treated with tyrosine kinase inhibitors • Nursing women • Known impaired cardiac function, including any of the following: • LVEF 470 msec for females and >450 msec for males on screening ECG. If QTc > 470 msec for females and > 450 msec for males and electrolytes are not within normal ranges before ponatinib dosing, elec-trolytes should be corrected and then the patient rescreened for QTcF criterion. • Myocardial infarction within 12 months prior to starting study treatment • Other clinical significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension) • Symptomatic peripheral vascular disease • Any history of ischemic stroke or transient ischemic attacks (TIAs) • History or presence of clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, cerebrovascular ischemia/haemorrhage, severe brain injuries, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis (with exception of CNS leukemia that is well con-trolled with intrathecal therapy) • History or active relevant autoimmune disease • Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation • Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) or active infection with Hepatitis B or C • History of pancreatitis within 6 months previous to start of treatment within the trial • Treatment with any other investigational agent or participating in another trial within 30 days prior to entering this study • Inadequate hepatic functions defined as ASAT or ALAT > 2,5 times the institutional upper limit of normal or > 5 times ULN if considered due to leukemia • Total bilirubin > 1.5-fold the institutional upper limit unless considered to be due to organ involvement by the leukemia or to M. Gilbert / M. Meulengracht • Concurrent severe diseases which exclude the administration of therapy e.g. severe, uncontrolled acute or chronic infections • Inability to understand and/or unwillingness to sign a written informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To prove non-inferiority in the overall survival (OS) of patients with Ph+ ALL and molecular CR treated with tyrosinkinase inhibitor (TKI), chemotherapy (chemo) alternating with Blina-tumomab (Blina) (TKI-Chemo-Blina) versus immediate SCT;Secondary Objective: To compare the rate of molecular complete remission after induction and first consolida-tion with chemotherapy and Ponatinib versus Imatinib. To evaluate the - molecular CR rate after Blina in patients with molecular failure (MolFail) - OS in subgroups in comparison with groups from previous GMALL trials - safety and efficacy of the treatment elements - quality of life (QoL), pt reported adverse events (PRAE) and comorbidities ;Primary end point(s): Probability of overall survival at 2,3 and 4 years from randomization I in patients with mo-lecular remission after consolidation 1 comparing a combination treatment of tyro-sinkinase inhibitor, Blinatumomab and chemotherapy versus the immediate SCT ;Timepoint(s) of evaluation of this end point: After 2, 3 and 4 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Rate of molecular complete remission at week 11 after consolidation with chemotherapy in combination with Ponatinb versus Imatinib. • Probability of remission duration, relapse-free survival, and cumulative incidence of re-lapse at different time-points in patients with molecular remission after consolidation 1 comparing a combination treatment of tyrosinkinase inhibitor, Blinatumomab and chemo-therapy versus the immediate SCT • Probability of Overall Survival, remission duration, relapse-free survival, and cumulative incidence of relapse at different time-points in patients with molecular persistence (molec-ular failure and MRD positivity below quantitative range) after consolidation 1 receiving blinatumomab combined with Ponatinib versus Imatinib followed by allogeneic stem cell transplantion • Relapse localisation and relapse characteristics including the frequency of patients with molecular relapse in proportion to total hematological relapse in o Patients transplanted in molecular remission after consolidation 1 o Patients with molecular remission after consolidation 1 receiving a combination treatment of ponatinib in combination with Blinatumomab and chemotherapy o Patients with molecular remission after consolidation 1 receiving a combination treatment of Imatinib in combination with Blinatumomab and chemotherapy o Patients with molecular persistence after consolidation 1 receiving a combination treatment of Imatinib in combination with Blinatumomab followed by allogeneic SCT o Patients with molecular persistence after consolidation 1 receiving a combination treatment of Ponatinib in combination with Blinatumomab followed by allogeneic SCT • Proportion of patients who achieve hematological and molecular remission or experience molecular failure treated with Ponatinib versus Imatinib at different time-points during in-duction and after first consolidation therapy • Overall incidence and severity of AEs in patients (CTC-AE 4.0) in | — |
Countries
Germany
Contacts
Public ContactGMALL-Studienzentrale
Goethe-University, Universitätsklinikum Frankfurt, Med. Klinik II
Outcome results
None listed