Treatment of Older Patients With B-precursor ALL With Sequential Dose Reduced Chemotherapy and Blinatumomab (EWALL-BOLD)

Goethe University

Status and phase: Completed; Phase 2

Conditions: B-Precursor ALL

Treatments: Drug: Blinatumomab

Study type: Interventional

Funder types: Other

Identifiers

NCT03480438

EWALL-BOLD

Details and patient eligibility

About

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.

Full 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.

Enrollment: 52 patients

Sex: All

Ages: 56 to 74 years old

Volunteers: No Healthy Volunteers

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 exclusion criteria to recommended chemotherapy

7. Known positivity of HIV, hepatitis B (HbsAG) or hepatitis C virus (anti-HCV)

8. Subject received prior anti-CD19 therapy

9. Live vaccination within 2 weeks before the start of study treatment

10. Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation:

    Subject has known sensitivity to immunoglobulins or any of the products or components to be administered during dosing

11. Currently receiving treatment in another investigational device or drug study or less than 30 days since ending treatment on another investigational device or drug study(s). Thirty days is calculated from day 1 of protocol-specified therapy

12. Subject likely to not be available to complete all protocol-required study visits or procedures, including follow-up visits, and/or to comply with all required study procedures to the best of the subject's and investigator's knowledge

13. History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator would pose a risk to subject safety of interfere with the study evaluation, procedures or completion

14. Woman of childbearing potential and is not willing to use a highly effective method of contraception while receiving study treatment and for an additional 3 months after the last dose of study treatment

15. Male who has a female partner of childbearing potential, and is not willing to use 2 highly effective forms of contraception while receiving protocol-specified therapy and for at least an additional 3 months after the last dose of protocol-specified therapy.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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52 participants in 1 patient group

Blinatumomab

Experimental group

Description:

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.

Treatment:

Drug: Blinatumomab