Phase II Trial for the Treatment of Older Patients With Newly Diagnosed CD19 Positive, Ph/BCR-ABL Negative B-precursor Acute Lymphoblastic Leukemia With Sequential Dose Reduced Chemotherapy and Blinatumomab (EWALL-BOLD)
Overview
- Phase
- Phase 2
- Intervention
- Blinatumomab
- Conditions
- B-Precursor ALL
- Sponsor
- Goethe University
- Enrollment
- 52
- Locations
- 21
- Primary Endpoint
- Hematologic and MRD response after induction therapy
- Status
- Completed
- Last Updated
- 7 months ago
Overview
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.
Investigators
Nicola Goekbuget
MD
Goethe University
Eligibility Criteria
Inclusion Criteria
- •Patients with newly diagnosed CD19 positive B-precursor ALL
- •Greater than 25 % blasts in bone marrow
- •Eastern Cooperative Oncology Group (ECOG) performance status \<= 2
- •Charlson comorbidity score \<= 2
- •Age \> 55 and \< 75 years at the time of informed consent
- •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)
Exclusion Criteria
- •Antileukemic pretreatment (GMALL prephase with dexamethasone and cyclophosphamide allowed)
- •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
- •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
- •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
- •Current autoimmune disease or history of autoimmune disease with potential CNS involvement
Arms & Interventions
Blinatumomab
Patients will receive blinatumomab at a dose of 28 μg/day as continuous intravenous infusion at constant flow rate for four weeks defined as one treatment cycle. Up to four cycles will be performed. In case of defined toxicities, the dose of blinatumomab may be reduced to 9 μg/day.
Intervention: Blinatumomab
Outcomes
Primary Outcomes
Hematologic and MRD response after induction therapy
Time Frame: 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 Outcomes
- Treatment deviation 1(until end of treatment (up to 39 weeks))
- Treatment deviation 5(until end of treatment (up to 39 weeks))
- Overall Survival(1 year after start of therapy)
- Adverse Events(continuously until end-of-core-study (week 43))
- MRD response after induction and consolidation(after induction and consolidation (up to 35 weeks))
- Time to MRD relapse(continuously until end of maintenance therapy (up to 27 months))
- Relapse localisation(In case of relapse, continuously until end of maintenance therapy (up to 27 months))
- Treatment deviation 2(until end of treatment (up to 39 weeks))
- Treatment deviation 3(until end of treatment (up to 39 weeks))
- Treatment deviation 4(until end of treatment (up to 39 weeks))
- Continuous complete remission(1 year after start of therapy)
- Relapse free survival(1 year after start of therapy)
- Quality of life(until end of maintenance therapy (up to 27 months))
- Event-free survival(1 year after start of therapy)