Sequential treatment with chemotherapy and Blinatumomab to improve the response and survival of patients affected by a form of cancer that affects the cells from which give origin to white cells (cells present in blood)
- Conditions
- Acute Lymphoblastic Leukemia Philadelphia Chromosome Negative (Ph-)MedDRA version: 21.0Level: LLTClassification code 10000844Term: Acute lymphoblastic leukaemiaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2017-004251-23-IT
- Lead Sponsor
- FONDAZIONE GIMEMA (GRUPPO ITALIANO MALATTIE EMATOLOGICHE DELL' ADULTO) FRANCO MANDELLI ONLUS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 149
1. Signed written informed consent according to ICH/EU/GCP and national local laws.
2. Age 18-65 years.
3. A diagnosis of untreated Ph- CD19+ BCP ALL is required, either de novo or secondary to chemo-radiotherapy for another cancer. Pre-treatment with low-dose corticosteroids in patients presenting with hyperleukocytosis is allowed. All diagnostic procedures need to be performed on freshly obtained bone marrow and blood samples.
4. Full cytological, cytochemical, cytogenetic and immunobiological disease characterization according to EGIL and WHO classifications.
5. BM and PB sampling are required for MRD evaluations. Detailed indications on patient registration, storage of representative diagnostic material and diagnostic work-up, including the forwarding of samples for MRD studies are given in Appendix A.
6. ECOG performance status 0-2, unless a performance of 3 is unequivocally caused by the disease itself and not by pre-existing comorbidity, that is considered and/or documented to be reversible following the application of anti-leukemic therapy and appropriate supportive measures.
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 145
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4
1. Diagnosis of Burkitt’s leukemia or lymphoma (mature B-ALL), Ph+ ALL, CD19- BCP ALL, T-ALL, lymphoblastic lymphoma (BM involvement by blast cells <25%).
2. Active CNS leukemia documented by diagnostic lumbar puncture on days -1 to -5 prior to the
first blinatumomab administration, or any other clinical sign or symptom ascribable to symptomatic/documented CNS disease at time of each planned blinatumomab course.
3. Down’s syndrome.
4. Pre-existing, uncontrolled pathology such as heart failure (congestive/ischemic, acute myocardial infarction within the past 3 months, untreatable arrhythmias, NYHA classes III and IV), severe liver disease with serum bilirubin >3 mg/dL and/or ALT >3 x upper normal limit (unless attributable to ALL), kidney function impairment with serum creatinine >2 mg/dL (unless attributable to ALL), and severe neuropsychiatric disorder that impairs the patient’s ability to understand and sign the informed consent, or to cope with the intended treatment plan. N.B. For altered liver and kidney function tests, eligibility criteria can be reassessed at 24-96 hours, following the institution of adequate supportive measures.
5. Presence of serious, active, uncontrolled infections.
6. Pre-existing HIV positive serology (i.e. already known before enrolment). If HIV positivity is detected after enrolment, the patient is sent off study.
7. A history of cancer that is not in a remission phase following surgery and/or radiotherapy and/or chemotherapy, with life expectancy <1 year.
8. Pregnancy declared by the patient herself, unless a decision is taken with the patient to induce a therapeutic abortion in order to carry on with ALL therapy. A pregnancy test is performed at diagnosis but does not preclude the enrolment into study. Fertile patients will be advised to adopt contraceptive methods while on treatment
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the trial is to assess the impact of blinatumomab in increasing the rate of early MRD negativiy at week 14 i.e. TP3 in adult patients with Ph- CD19+ BCP ALL in first CR.;Secondary Objective: 1. Complete remission (CR)<br>2. Disease-free survival (DFS)<br>3. Overall survival (OS)<br>4. Cumulative incidence of relapse (CIR)<br>5. Bone marrow MRD response at weeks 4, 10, 23 and 30, i.e. TPs 1, 2, 4 and 5<br>6. Treatment-related mortality (TRM)<br>7. MRD negativity, DFS, OS, CIR and TRM according to patient age, diagnostic ALL subset and risk category<br>8. MRD monitoring<br>9. Safety;Primary end point(s): L'endpoint primario di questo studio è di aumentare il tasso di negatività della MRD precoce ottenuto dopo il primo ciclo di blinatumomab (MRD TP3 / settimana 14) in pazienti adulti con ALL-BCP Ph-CD19 +.;Timepoint(s) of evaluation of this end point: Week 14
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Complete remission (CR) after induction chemotherapy course 1 or 2.<br>2. Disease-free survival (DFS) at 36 months<br>3. Overall survival (OS) at 36 months<br>4. Cumulative incidence of relapse (CIR) at 36 months<br>5. Percentage of patients with bone marrow MRD negative, weakly positive =10-4, and positive<br>=10-4 or 10-3 at weeks 4-30, i.e. TPs 1-5<br>6. Treatment-related mortality (TRM)<br>7. DFS, OS, CIR and TRM in different age groups, diagnostic ALL subsets and risk categories<br>8. MRD levels at different time points<br>9. Safety in terms of number and rate of adverse events and serious adverse events.;Timepoint(s) of evaluation of this end point: After 1st and 2nd cycle of chemotherapy (CR)<br>At 36 months (OS, DFS, CIR)<br>MRD every 3 months<br>At the end of the study