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

Sponsor
Goethe University (Other)
Overall Status
Recruiting
CT.gov ID
NCT03480438
Collaborator
(none)
50
Enrollment
21
Locations
1
Arm
67
Anticipated Duration (Months)
2.4
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
50 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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)
Actual Study Start Date :
Jun 1, 2018
Anticipated Primary Completion Date :
Sep 1, 2023
Anticipated Study Completion Date :
Jan 1, 2024

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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 Outcome Measures

    1. Overall Survival [1 year after start of therapy]

      Probability of overall survival at 1 year after start of therapy

    2. 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

    3. 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

    4. 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

    5. Continuous complete remission [1 year after start of therapy]

      Probability of continuous complete remission at 1 year

    6. Relapse free survival [1 year after start of therapy]

      Probability of relapse free survival at 1 year

    7. Event-free survival [1 year after start of therapy]

      Probability of event-free survival at 1 year

    8. 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

    9. Quality of life Score [until end of maintenance therapy (up to 27 months)]

      Quality of life measures (EORTC standard scales) at different time-points during induction and consolidation

    10. Treatment deviation 1 [until end of treatment (up to 39 weeks)]

      Rate of treatment interruptions

    11. Treatment deviation 2 [until end of treatment (up to 39 weeks)]

      Duration of treatment interruptions

    12. Treatment deviation 3 [until end of treatment (up to 39 weeks)]

      Dose reductions

    13. Treatment deviation 4 [until end of treatment (up to 39 weeks)]

      Mitigation strategies

    14. Treatment deviation 5 [until end of treatment (up to 39 weeks)]

      Rate of withdrawals

    Other Outcome Measures

    1. Hospitalisation time [until end of treatment (up to 39 weeks)]

      Number of hospitalisation days

    2. Infusion pump systems [until end of treatment (up to 39 weeks)]

      Use of infusion pump systems

    3. Ambulatory care services [until end of treatment (up to 39 weeks)]

      Use of ambulatory care services

    4. 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    56 Years to 74 Years
    Sexes Eligible for Study:
    All
    Accepts 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)

    1. Negative pregnancy test in women of childbearing potential

    2. Ability to understand and willingness to sign a written informed consent

    3. 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

    1. 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

    2. 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

    3. Current autoimmune disease or history of autoimmune disease with potential CNS involvement

    4. Known exclusion criteria to recommended chemotherapy

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

    6. Subject received prior anti-CD19 therapy

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

    8. 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

    1. 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

    2. 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

    3. 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

    4. 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

    5. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University Hospital of Frankfurt (Main) Frankfurt (Main) Hessen Germany 60590
    2 Uniklinik RWTH Aachen Aachen Germany
    3 Charité - Campus Benjamin Franklin Berlin Germany
    4 Vivantes Klinikum Neukölln Berlin Germany
    5 Städtisches Klinikum Braunschweig Braunschweig Germany
    6 Klinikum Bremen Mitte Bremen Germany
    7 Evangelisches Krankenhaus Essen-Werden Essen Germany
    8 Universitätsklinikum Halle Halle (Saale) Germany
    9 Uniklinik Hamburg Eppendorf Hamburg Germany
    10 Evangelisches Krankenhaus Hamm Hamm Germany
    11 Städtisches Klinikum Karlsruhe Karlsruhe Germany
    12 Universitätsklinikum Schleswig-Holstein Kiel Germany
    13 Gemeinschaftsklinikum Mittelrhein Koblenz Germany
    14 Universitätsklinikum Leipzig Leipzig Germany
    15 Klinikum Großhadern München Germany
    16 Klinikum rechts der Isar der TU München München Germany
    17 Klinikum Oldenburg Oldenburg Germany
    18 Universitätsklinik Tübingen Tübingen Germany
    19 Universitätsklinikum Ulm Ulm Germany
    20 Helios Klinikum Wuppertal Wuppertal Germany
    21 Uniklinik Würzburg Würzburg Germany

    Sponsors and Collaborators

    • Goethe University

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Nicola Goekbuget, MD, Goethe University
    ClinicalTrials.gov Identifier:
    NCT03480438
    Other Study ID Numbers:
    • EWALL-BOLD
    First Posted:
    Mar 29, 2018
    Last Update Posted:
    Aug 18, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Blinatumomab

    Study Results

    No Results Posted as of Aug 18, 2022