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Trial record 1 of 1 for:    EWALL-BOLD | All | Germany
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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 : July 29, 2020
Sponsor:
Information provided by (Responsible Party):
Nicola Goekbuget, Goethe University

Tracking Information
First Submitted Date  ICMJE March 12, 2018
First Posted Date  ICMJE March 29, 2018
Last Update Posted Date July 29, 2020
Actual Study Start Date  ICMJE June 1, 2018
Estimated Primary Completion Date September 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 21, 2018)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 29, 2018)
  • Overall Survival [ Time Frame: 1 year after start of therapy ]
    Probability of overall survival at 1 year after start of therapy
  • 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
  • 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
  • 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
  • Continuous complete remission [ Time Frame: 1 year after start of therapy ]
    Probability of continuous complete remission at 1 year
  • Relapse free survival [ Time Frame: 1 year after start of therapy ]
    Probability of relapse free survival at 1 year
  • Event-free survival [ Time Frame: 1 year after start of therapy ]
    Probability of event-free survival at 1 year
  • 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
  • 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
  • Treatment deviation 1 [ Time Frame: until end of treatment (up to 39 weeks) ]
    Rate of treatment interruptions
  • Treatment deviation 2 [ Time Frame: until end of treatment (up to 39 weeks) ]
    Duration of treatment interruptions
  • Treatment deviation 3 [ Time Frame: until end of treatment (up to 39 weeks) ]
    Dose reductions
  • Treatment deviation 4 [ Time Frame: until end of treatment (up to 39 weeks) ]
    Mitigation strategies
  • Treatment deviation 5 [ Time Frame: until end of treatment (up to 39 weeks) ]
    Rate of withdrawals
Original Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2018)
  • Overall Survival [ Time Frame: 1 year after start of therapy ]
    Probability of overall survival at 1 year after start of therapy
  • 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
  • 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
  • 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
  • Continuous complete remission [ Time Frame: 1 year after start of therapy ]
    Probability of continuous complete remission at 1 year
  • Relapse free survival [ Time Frame: 1 year after start of therapy ]
    Probability of relapse free survival at 1 year
  • Event-free survival [ Time Frame: 1 year after start of therapy ]
    Probability of event-free survival at 1 year
  • 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
  • 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
  • Treatment deviations [ Time Frame: until end of treatment (up to 39 weeks) ]
    Rate and duration of treatment interruptions, dose reductions, mitigation strategies and rate of withdrawals
Current Other Pre-specified Outcome Measures
 (submitted: March 29, 2018)
  • Hospitalisation time [ Time Frame: until end of treatment (up to 39 weeks) ]
    Number of hospitalisation days
  • Infusion pump systems [ Time Frame: until end of treatment (up to 39 weeks) ]
    Use of infusion pump systems
  • Ambulatory care services [ Time Frame: until end of treatment (up to 39 weeks) ]
    Use of ambulatory care services
  • 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
Original Other Pre-specified Outcome Measures
 (submitted: March 21, 2018)
  • Hospitalisation time, infusion pump systems, ambulatory care services [ Time Frame: until end of treatment (up to 39 weeks) ]
    Document and analyse hospitalisation time, use of infusion pump systems, use of ambulatory care services
  • 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
 
Descriptive Information
Brief Title  ICMJE Treatment of Older Patients With B-precursor ALL With Sequential Dose Reduced Chemotherapy and Blinatumomab
Official Title  ICMJE 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)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE B-Precursor ALL
Intervention  ICMJE Drug: Blinatumomab
Patients will receive standard of care chemotherapy before blinatumomab, between blinatumomab cycles and after blinatumomab.
Other Name: blincyto
Study Arms  ICMJE 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.

Intervention: Drug: Blinatumomab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 21, 2018)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 1, 2023
Estimated Primary Completion Date September 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 56 Years to 74 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Nicola Goekbuget, MD +49 (0)69 - 6301 ext 6365 goekbuget@em.uni-frankfurt
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03480438
Other Study ID Numbers  ICMJE EWALL-BOLD
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Nicola Goekbuget, Goethe University
Study Sponsor  ICMJE Goethe University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Nicola Goekbuget, MD Johann Wolfgang Goethe University Hospital
PRS Account Goethe University
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP