Clinical Trials /

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

NCT03480438

Description:

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.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Treatment of Older Patients With B-precursor ALL With Sequential Dose Reduced Chemotherapy and Blinatumomab
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: EWALL-BOLD
  • NCT ID: NCT03480438

Conditions

  • B-Precursor ALL

Interventions

DrugSynonymsArms
BlinatumomabblincytoBlinatumomab

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
BlinatumomabExperimentalPatients 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.
  • Blinatumomab

Eligibility 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.
      
Maximum Eligible Age:74 Years
Minimum Eligible Age:56 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Goethe University

Last Updated