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

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)

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.

Study Overview

• Status: Completed
• Conditions: B-Precursor ALL
• Intervention / Treatment: Drug: Blinatumomab

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.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany
    • Uniklinik RWTH Aachen
  • Berlin, Germany
    • Charite - Campus Benjamin Franklin
  • Berlin, Germany
    • Vivantes Klinikum Neukölln
  • Braunschweig, Germany
    • Städtisches Klinikum Braunschweig
  • Bremen, Germany
    • Klinikum Bremen Mitte
  • Essen, Germany
    • Evangelisches Krankenhaus Essen-Werden
  • Halle, Germany
    • Universitatsklinikum Halle
  • Hamburg, Germany
    • Uniklinik Hamburg Eppendorf
  • Hamm, Germany
    • Evangelisches Krankenhaus Hamm
  • Karlsruhe, Germany
    • Stadtisches Klinikum Karlsruhe
  • Kiel, Germany
    • Universitätsklinikum Schleswig-Holstein
  • Koblenz, Germany
    • Gemeinschaftsklinikum Mittelrhein
  • Leipzig, Germany
    • Universitätsklinikum Leipzig
  • München, Germany
    • Klinikum Großhadern
  • München, Germany
    • Klinikum rechts der Isar der TU München
  • Oldenburg, Germany
    • Klinikum Oldenburg
  • Tübingen, Germany
    • Universitätsklinik Tübingen
  • Ulm, Germany
    • Universitatsklinikum Ulm
  • Wuppertal, Germany
    • Helios Klinikum Wuppertal
  • Würzburg, Germany
    • Uniklinik Würzburg
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60590
      • University Hospital of Frankfurt (Main)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 56 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Blinatumomab; Patients will receive standard of care chemotherapy before blinatumomab, between blinatumomab cycles and after blinatumomab.; Other Names: blincyto

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hematologic and MRD response after induction therapy	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	after induction therapy (up to 8 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Probability of overall survival at 1 year after start of therapy	1 year after start of therapy
Adverse Events	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	continuously until end-of-core-study (week 43)
MRD response after induction and consolidation	Proportion of patients who achieve a MRD response or a complete MRD response after induction consolidation	after induction and consolidation (up to 35 weeks)
Time to MRD relapse	Time to MRD relapse after prior achievement of MRD response or complete MRD response	continuously until end of maintenance therapy (up to 27 months)
Continuous complete remission	Probability of continuous complete remission at 1 year	1 year after start of therapy
Relapse free survival	Probability of relapse free survival at 1 year	1 year after start of therapy
Event-free survival	Probability of event-free survival at 1 year	1 year after start of therapy
Relapse localisation	Proportion of different relapse localisation in relation to total number of relapses	In case of relapse, continuously until end of maintenance therapy (up to 27 months)
Treatment deviation 1	Rate of treatment interruptions	until end of treatment (up to 39 weeks)
Treatment deviation 2	Duration of treatment interruptions	until end of treatment (up to 39 weeks)
Treatment deviation 3	Dose reductions	until end of treatment (up to 39 weeks)
Treatment deviation 4	Mitigation strategies	until end of treatment (up to 39 weeks)
Treatment deviation 5	Rate of withdrawals	until end of treatment (up to 39 weeks)
Quality of life	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/)	until end of maintenance therapy (up to 27 months)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalisation time	Number of hospitalisation days	until end of treatment (up to 39 weeks)
Infusion pump systems	Use of infusion pump systems	until end of treatment (up to 39 weeks)
Ambulatory care services	Use of ambulatory care services	until end of treatment (up to 39 weeks)
Biologic markers	Measurement of biologic markers in bone marrow and peripheral blood throughout induction and consolidation therapy	continuously until end of consolidation therapy (up to 35 weeks)

Collaborators and Investigators

• Sponsor: Goethe University
• Investigators: Study Director: Nicola Goekbuget, MD, Johann Wolfgang Goethe University Hospital

Publications and helpful links

Helpful Links

• Trial register of the Kompetenznetz Leukaemie
• Clinical Trials Register Results

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Actual): January 10, 2024
• Study Completion (Actual): January 10, 2024

Study Registration Dates

• First Submitted: March 12, 2018
• First Submitted That Met QC Criteria: March 21, 2018
• First Posted (Actual): March 29, 2018

Study Record Updates

• Last Update Posted (Estimated): October 3, 2025
• Last Update Submitted That Met QC Criteria: September 30, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Infections; Virus Diseases; Neoplasms by Histologic Type; DNA Virus Infections; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Epstein-Barr Virus Infections; Herpesviridae Infections; Tumor Virus Infections; Hemic and Lymphatic Diseases; Burkitt Lymphoma; Antineoplastic Agents; blinatumomab
• Other Study ID Numbers: EWALL-BOLD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No