B-Precursor ALL
Conditions
Brief summary
The trial proposed here attempts to reduce induction chemotherapy to phase I of standard induction in patients with B-precursor ALL. Induction phase II will be replaced by blinatumomab. The initial treatment phase is followed by sequential chemotherapy and further blinatumomab cycles.
Detailed description
Blinatumomab is a bispecific single-chain antibody construct designed to link B cells and T cells resulting in T-cell activation and a cytotoxic T-cell response against CD19 expressing cells. In Phase II-III clinical trials 43-69 % of the patients treated with blinatumomab in relapsed/refractory ALL with poor prognostic features, achieved a complete hematologic remission and around 80 % of these obtained a molecular remission as well. Blinatumomab thus has demonstrated significant antileukemic activity in relapsed/refractory adult ALL. The ultimate goal for optimised management of adult ALL is to integrate targeted compounds with known single-drug activity into first-line treatment.
Interventions
DRUGBlinatumomab
Patients will receive standard of care chemotherapy before blinatumomab, between blinatumomab cycles and after blinatumomab.
Sponsors
Goethe University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
56 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with newly diagnosed CD19 positive B-precursor ALL 2. Greater than 25 % blasts in bone marrow 3. Eastern Cooperative Oncology Group (ECOG) performance status \<= 2 4. Charlson comorbidity score \<= 2 5. Age \> 55 and \< 75 years at the time of informed consent 6. Renal and hepatic function as defined below: * AST (SGOT), ALT(SGPT) and AP \< 5x upper limit of normal (UNL) (unless related to leukemic liver infiltration by investigator assessment) * Total bilirubin \< 1.5x ULN (unless related to Gilbert's Meulengracht disease) * Creatinine \< 1.5x ULN * Creatinine clearance \>= 50 mL/min (e.g. calculated according Cockroft & Gault) 7. Negative pregnancy test in women of childbearing potential 8. Ability to understand and willingness to sign a written informed consent 9. For Germany: Participation in the registry of the German Multicenter Study Group for Adult ALL (GMALL)
Exclusion criteria
1. Antileukemic pretreatment (GMALL prephase with dexamethasone and cyclophosphamide allowed) 2. History of malignancy other than ALL within 5 years prior to start of protocol-specified therapy with the exception of: * Malignancy treated with curative intent and with no known active disease present for 2 years before enrollment and felt to be at low risk for recurrence by the treating physician including * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence 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 3. History or presence of clinically relevant (per investigator's assessment) CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome or psychosis 4. Active ALL in the CNS confirmed by CSF analysis) or testes (clinical diagnosis) or other extramedullary involvement; non-bulky lymph node (\< 7.5 cm diameter) involvement will be accepted 5. Current autoimmune disease or history of autoimmune disease with potential CNS involvement 6. Known
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hematologic and MRD response after induction therapy | after induction therapy (up to 8 weeks) | Proportion of patients achieving a complete hematologic remission and a complete molecular remission (MRD response or complete MRD response) after induction therapy defined as one cycle of chemotherapy and one cycle of blinatumomab |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relapse free survival | 1 year after start of therapy | Probability of relapse free survival at 1 year |
| Treatment deviation 2 | until end of treatment (up to 39 weeks) | Duration of treatment interruptions |
| Treatment deviation 3 | until end of treatment (up to 39 weeks) | Dose reductions |
| Treatment deviation 4 | until end of treatment (up to 39 weeks) | Mitigation strategies |
| Treatment deviation 5 | until end of treatment (up to 39 weeks) | Rate of withdrawals |
| Overall Survival | 1 year after start of therapy | Probability of overall survival at 1 year after start of therapy |
| Adverse Events | continuously until end-of-core-study (week 43) | Rate and grade of adverse events (AE) according to CTC-AE in induction phase I, blinatumomab induction and during blinatumomab cycle I, II and III |
| MRD response after induction and consolidation | after induction and consolidation (up to 35 weeks) | Proportion of patients who achieve a MRD response or a complete MRD response after induction consolidation |
| Time to MRD relapse | continuously until end of maintenance therapy (up to 27 months) | Time to MRD relapse after prior achievement of MRD response or complete MRD response |
| Continuous complete remission | 1 year after start of therapy | Probability of continuous complete remission at 1 year |
| Event-free survival | 1 year after start of therapy | Probability of event-free survival at 1 year |
| Relapse localisation | In case of relapse, continuously until end of maintenance therapy (up to 27 months) | Proportion of different relapse localisation in relation to total number of relapses |
| Quality of life | until end of maintenance therapy (up to 27 months) | Quality of life measures (EORTC=European Organisation for Research and Treatment of Cancer standard scales) at different time-points during induction and consolidation; this is a multidimensional questionnaire with different scales per item such als functional scale, global health status and symptoms. Details are outlined in respective manuals (https://qol.eortc.org/manuals/) |
| Treatment deviation 1 | until end of treatment (up to 39 weeks) | Rate of treatment interruptions |
Other
| Measure | Time frame | Description |
|---|---|---|
| Ambulatory care services | until end of treatment (up to 39 weeks) | Use of ambulatory care services |
| Biologic markers | continuously until end of consolidation therapy (up to 35 weeks) | Measurement of biologic markers in bone marrow and peripheral blood throughout induction and consolidation therapy |
| Infusion pump systems | until end of treatment (up to 39 weeks) | Use of infusion pump systems |
| Hospitalisation time | until end of treatment (up to 39 weeks) | Number of hospitalisation days |
Countries
Germany
Outcome results
None listed