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

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ClinicalTrials.gov Identifier: NCT03480438
Recruitment Status : Recruiting
First Posted : March 29, 2018
Last Update Posted : May 4, 2021
Sponsor:
Information provided by (Responsible Party):
Nicola Goekbuget, Goethe University

Study Description
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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
B-Precursor ALL Drug: Blinatumomab 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
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Study Type : Interventional  (Clinical Trial)
Estimated 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 : June 1, 2018
Estimated Primary Completion Date : September 1, 2022
Estimated Study Completion Date : January 1, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: blincyto


Outcome Measures
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Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Overall Survival [ Time Frame: 1 year after start of therapy ]
    Probability of overall survival at 1 year after start of therapy

  2. Adverse Events [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 1 year after start of therapy ]
    Probability of continuous complete remission at 1 year

  6. Relapse free survival [ Time Frame: 1 year after start of therapy ]
    Probability of relapse free survival at 1 year

  7. Event-free survival [ Time Frame: 1 year after start of therapy ]
    Probability of event-free survival at 1 year

  8. Relapse localisation [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: until end of treatment (up to 39 weeks) ]
    Rate of treatment interruptions

  11. Treatment deviation 2 [ Time Frame: until end of treatment (up to 39 weeks) ]
    Duration of treatment interruptions

  12. Treatment deviation 3 [ Time Frame: until end of treatment (up to 39 weeks) ]
    Dose reductions

  13. Treatment deviation 4 [ Time Frame: until end of treatment (up to 39 weeks) ]
    Mitigation strategies

  14. Treatment deviation 5 [ Time Frame: until end of treatment (up to 39 weeks) ]
    Rate of withdrawals


Other Outcome Measures:
  1. Hospitalisation time [ Time Frame: until end of treatment (up to 39 weeks) ]
    Number of hospitalisation days

  2. Infusion pump systems [ Time Frame: until end of treatment (up to 39 weeks) ]
    Use of infusion pump systems

  3. Ambulatory care services [ Time Frame: until end of treatment (up to 39 weeks) ]
    Use of ambulatory care services

  4. Biologic markers [ Time Frame: 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
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Ages Eligible for Study:   56 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03480438


Contacts
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Contact: Nicola Goekbuget, MD +49 (0)69 - 6301 ext 6365 goekbuget@em.uni-frankfurt

Locations
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Sponsors and Collaborators
Goethe University
Investigators
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Study Director: Nicola Goekbuget, MD Johann Wolfgang Goethe University Hospital
More Information
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Additional Information:

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Responsible Party: Nicola Goekbuget, MD, Goethe University
ClinicalTrials.gov Identifier: NCT03480438    
Other Study ID Numbers: EWALL-BOLD
First Posted: March 29, 2018    Key Record Dates
Last Update Posted: May 4, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Blinatumomab
Antineoplastic Agents