Clinical Trials /

Blinatumomab in Adult Patients With Minimal Residual Disease (MRD) of B-precursor Acute Lymphoblastic Leukemia

NCT03109093

Description:

This study is designed to confirm the efficacy, safety, and tolerability of blinatumomab in patients with MRD of B- precursor ALL in complete hematological remission including patients with relapse after SCT. The study aims to expand experience generated in previous trials in patients with MRD positive ALL with a focus on additional specific questions.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Blinatumomab in Adult Patients With Minimal Residual Disease (MRD) of B-precursor Acute Lymphoblastic Leukemia
  • Official Title: A Multicenter, Single-arm Study to Assess the Efficacy, Safety, and Tolerability of the BiTE® Antibody Blinatumomab in Adult Patients With Minimal Residual Disease (MRD) of B-precursor Acute Lymphoblastic Leukemia (Blast Successor Trial)

Clinical Trial IDs

  • ORG STUDY ID: GMALL-MOLACT1-BLINA
  • SECONDARY ID: 2015-000733-76
  • NCT ID: NCT03109093

Conditions

  • ALL, Recurrent, Adult

Interventions

DrugSynonymsArms
BlinatumomabblincytoBlinatumomab

Purpose

This study is designed to confirm the efficacy, safety, and tolerability of blinatumomab in patients with MRD of B- precursor ALL in complete hematological remission including patients with relapse after SCT. The study aims to expand experience generated in previous trials in patients with MRD positive ALL with a focus on additional specific questions.

Detailed Description

      Transfer of patients to alloHSCT after one cycle or after subsequent cycles is considered as
      per protocol discontinuation and as premature treatment discontinuation In case of
      hematological or extramedullary relapse, the study treatment will be permanently
      discontinued.

      There will be a safety follow-up visit at 30 days after end of the last infusion. There will
      be efficacy follow-up until 18 months after treatment start. In patients scheduled for SCT
      the 30-day safety-visit may be performed at the latest time point possible before initiation
      of subsequent treatment.
    

Trial Arms

NameTypeDescriptionInterventions
BlinatumomabExperimentalPatients will receive four cycles of treatment, unless criteria for treatment discontinuation apply. The duration of one cycle is 6 weeks, including a four week continuous intravenous infusion and a two week infusion free interval, which may be extended by a maximum of 7 days. Transfer of patients to alloHSCT after one cycle or after subsequent cycles is considered as per protocol discontinuation and as premature treatment discontinuation In case of hematological or extramedullary relapse, the study treatment will be permanently discontinued.
  • Blinatumomab

Eligibility Criteria

        Inclusion Criteria:

          1. Patients with CD19 positive B-precursor ALL in complete hematological remission
             defined as less than 5% blasts in bone marrow after at least three intense
             chemotherapy blocks (e.g., GMALL induction I-II/consolidation I).

          2. Presence of minimal residual disease (MRD) at a level of ≥10-4 (molecular failure or
             molecular relapse) in an assay with a minimum sensitivity of 10-4 documented after an
             interval of at least 2 weeks from last systemic chemotherapy

          3. For evaluation of MRD patients must have at least one molecular marker based on
             individual rearrangements of immunoglobulin, TCR-genes or other suitable genes
             evaluated by the reference laboratory of the trial

          4. Bone marrow function as defined below:

               -  ANC (Neutrophils) >= 1,000/µL

               -  Platelets >= 50,000/µL (transfusion permitted)

               -  HB level >= 9g/dl (transfusion permitted)

          5. Renal and hepatic function as defined below:

               -  AST (GOT), ALT (GPT), and AP < 5 x upper limit of normal (ULN)

               -  Total bilirubin < 1.5 x ULN (unless related to Gilbert's Meulengracht disease)

               -  Creatinine < 1.5x ULN

               -  Creatinine clearance >= 60 mL/min (e.g. calculated according Cockroft&Gault)

          6. Negative HIV test, negative hepatitis B (HbsAg) and hepatitis C virus (anti-HCV) test

          7. Negative pregnancy test in women of childbearing potential

          8. ECOG Performance Status 0 or 1

          9. Age >=18 years

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

         11. Signed and dated written informed consent is available

         12. Participation in the registry of the German Multicenter Study Group for Adult ALL
             (GMALL)

        Exclusion Criteria:

          1. Ph/BCR-ABL positive ALL

          2. Presence of circulating blasts or current extramedullary involvement by ALL

          3. History or presence of clinically relevant CNS pathology (e.g. seizure, paresis,
             aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia,
             Parkinson's disease, cerebellar disease, organic brain syndrome or psychosis)

          4. Current detection of ALL blast cells in cerebro-spinal fluid

          5. History of or active relevant autoimmune disease

          6. Systemic cancer chemotherapy within 2 weeks prior to study treatment (except for
             intrathecal prophylaxis)

          7. Radiotherapy within 4 weeks prior to study treatment

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

          9. Autologous hematopoietic stem cell transplantation (SCT) within six weeks prior to
             study treatment

         10. Allogeneic SCT within 12 weeks before the start of study treatment

         11. Any active acute Graft-versus-Host Disease (GvHD), grade 2-4 according to the
             Glucksberg criteria or active chronic GvHD requiring systemic treatment

         12. Any systemic therapy against GvHD within 2 weeks before start of study treatment

         13. Therapy with monoclonal antibodies (rituximab, alemtuzumab) within 4 weeks prior to
             study treatment

         14. Treatment with any investigational product within four weeks prior to study treatment

         15. Previous treatment with blinatumomab or other anti-CD19-therapy

         16. Known hypersensitivity to immunoglobulins or to any other component of the study drug
             formulation

         17. History of malignancy other than ALL diagnosed within 5 years prior to start of
             protocol-specified therapy with the exception of:

               -  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

         18. Active infection, any other concurrent disease or medical condition that are deemed to
             interfere with the conduct of the study as judged by the investigator

         19. Nursing women

         20. Woman of childbearing potential and is not willing to use 2 highly effective methods
             of contraception while receiving study treatment and for an additional 3 months after
             the last dose of study treatment.

         21. Male who has a female partner of childbearing potential, and is not willing to use 2
             highly effective forms of contraception while receiving study treatment and for at
             least an additional 3 months after the last dose of study treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:MRD response after one cycle
Time Frame:after one cycle of treatment (up to 43 days)
Safety Issue:
Description:Proportion of patients who achieve complete MRD response after one cycle of treatment with blinatumomab in patients with and without prior SCT

Secondary Outcome Measures

Measure:Continuous complete remission
Time Frame:18 months following initiation of blinatumomab
Safety Issue:
Description:Probability of continuous complete remission (remission duration) at 18 months following initiation of blinatumomab
Measure:Hematological relapse-free survival
Time Frame:18 months following initiation of blinatumomab
Safety Issue:
Description:Probability of hematological relapse-free survival rate at 18 months following initiation of blinatumomab
Measure:Overall survival
Time Frame:18 months following initiation of blinatumomab
Safety Issue:
Description:Probability of overall survival at 18 months following initiation of blinatumomab
Measure:Relapse localisations
Time Frame:In Case of Relapse, continuously until End of Follow-Up (up to 18 Months)
Safety Issue:
Description:Frequency of different relapse localisations in proportion to total hematological relapses
Measure:Biological evaluation of hematological and extramedullary relapse
Time Frame:In Case of Relapse, continuously until End of Follow-Up (up to 18 Months)
Safety Issue:
Description:Biological evaluation of hematological and extramedullary relapses including CD19 expression
Measure:Serious Adverse Event (SAE) incidence
Time Frame:continuously until End of Safety-Follow-Up (up to 26 weeks)
Safety Issue:
Description:Overall incidence and severity of adverse events in patients with and without prior SCT (CTCAE 4.0)
Measure:MRD response after two cycles
Time Frame:after two cycles of treatment (up to 85 days)
Safety Issue:
Description:Proportion of patients who achieve complete MRD response after two cycles of treatment with blinatumomab in patients with and without prior SCT
Measure:duration of MRD response
Time Frame:18 months following initiation of blinatumomab
Safety Issue:
Description:Probability of continuous MRD response and complete MRD response and duration of MRD response at 18 months following initiation of blinatumomab
Measure:Time to MRD response
Time Frame:MRD determination after each cycle of treatment (up to 24 weeks)
Safety Issue:
Description:Time to MRD response measured by time-point of first achievement
Measure:GvHD
Time Frame:until End of Safety-Follow-Up (up to 26 weeks)
Safety Issue:
Description:Evaluation of GvHD as part of AE documentation and according to Glucksberg Criteria, grade and localisation.
Measure:treatment related mortality after subsequent SCT
Time Frame:after subsequent SCT (at day 100 and later)
Safety Issue:
Description:• Evaluation of overall survival, remission duration, relapse-free survival and treatment related mortality (at day 100 and later) in patients with SCT in complete remission after blinatumomab
Measure:treatment related mortality
Time Frame:continuously until End of Follow-Up (up to 18 Months)
Safety Issue:
Description:Evaluation of overall survival, remission duration, relapse-free survival and treatment related mortality in patients without SCT in complete remission after blinatumomab
Measure:Quality of Life
Time Frame:until End of Follow-Up (up to 18 Months)
Safety Issue:
Description:Measurement of Quality of Life with EORTC instruments (EORTC QLQ C30 and EQ-5D) at different time-points during treatment

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Goethe University

Trial Keywords

  • ALL
  • acute lymphoblastic leukemia
  • MRD positive
  • minimal residual disease
  • blinatumomab

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