Clinical Trials /

Blinatumomab and Tyrosine Kinase Inhibitor Therapy in People With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

NCT04329325

Description:

: The purpose of this study is to test whether blinatumomab in combination with TKI therapy (such as dasatinib) is an effective treatment for people with Ph+ ALL. Researchers want to improve the response to standard-of-care treatment of corticosteroids + TKI therapy by adding the study drug, blinatumomab.

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Blinatumomab and Tyrosine Kinase Inhibitor Therapy in People With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
  • Official Title: Phase II Study of Blinatumomab and Concurrent Oral Tyrosine Kinase Inhibitor Therapy as Consolidation and Maintenance Therapy for Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Following Chemotherapy-Sparing Induction

Clinical Trial IDs

  • ORG STUDY ID: 19-343
  • NCT ID: NCT04329325

Conditions

  • Acute Lymphoblastic Leukemia
  • Philadelphia Chromosome-Positive

Interventions

DrugSynonymsArms
BlinatumomabBlinatumomab & Concurrent Oral Tyrosine Kinase Inhibitor Ther
corticosteroidsBlinatumomab & Concurrent Oral Tyrosine Kinase Inhibitor Ther

Purpose

The purpose of this study is to test whether blinatumomab in combination with TKI therapy is an effective treatment for people with Ph+ ALL. Researchers want to improve the response to standard-of-care treatment of corticosteroids + TKI therapy by adding the study drug, blinatumomab. The study will also test the safety of blinatumomab in combination with the TKI therapy drug dasatinib.

Trial Arms

NameTypeDescriptionInterventions
Blinatumomab & Concurrent Oral Tyrosine Kinase Inhibitor TherExperimentalPatients may receive corticosteroids and/or hydroxyurea at the discretion of the treating physician prior to beginning induction therapy. A seven-day corticosteroid pre-phase, which can include days of corticosteroid receipt prior to protocol registration, will precede initiation of TKI therapy on day 1.
  • Blinatumomab
  • corticosteroids

Eligibility Criteria

        Inclusion Criteria:

          -  Able to give informed consent

          -  Age ≥ 18 years of age

          -  Direct bilirubin ≤2x upper limit of normal (ULN), AST and ALT ≤10x upper limit of
             normal (ULN). Higher bilirubin and AST/ALT levels are acceptable if thought related to
             Ph+ ALL.

          -  Confirmed diagnosis of acute lymphoblastic leukemia (ALL) by morphology,
             immunohistochemistry, and/or multiparameter flow cytometry, with confirmation of
             Philadelphia chromosome positivity (Ph+) by cytogenetic studies (karyotype/FISH),
             molecular studies (BCRABL1 fusion transcripts), or targeted RNA sequencing

          -  No prior therapy for ALL beyond corticosteroids, hydroxyurea, or prophylactic
             intrathecal/intra-Ommaya chemotherapy Acceptable end-organ function (i.e. not meeting
             exclusion criteria below)

          -  Amenable to practicing an effective method of birth control during treatment and for
             at least 3 months following treatment on study

          -  ECOG performance status 0-2

        Exclusion Criteria:

          -  Philadelphia chromosome-negative ALL

          -  Mature B-cell ALL (e.g. Burkitt leukemia/lymphoma)

          -  Active extramedullary disease at time of study entry, including known CNS-3 disease
             (≥5 WBC/microliter and positive cytology or flow cytometry). Note: LP and/or CNS
             imaging prior to treatment initiation is not required, but if the patient is found to
             have active CNS-3 disease (by LP) or evidence of CNS involvement on imaging in the
             course of evaluation of clinical findings, enrollment is not permissible.

          -  Presence of known ABL kinase mutations conferring resistance to dasatinib at time of
             study entry, including T315I mutation. Note: ABL mutation testing prior to treatment
             initiation is neither recommended nor required, but if results of such mutation
             testing are known, enrollment of a patient with known ABL kinase mutations conferring
             dasatinib resistance is not permissible.

          -  Unable to tolerate initial therapy with dasatinib in the determination of the
             investigator, or unable to tolerate oral medication.

          -  Creatinine >1.5x upper limit of normal and estimated GFR <30 mL/min (based on 24-hour
             urine collection to determine creatine clearance or CKD-EPI equation)

          -  Heart disease meeting one or more of the following criteria:

               -  New York Heart Association (NYHA) stage III or IV congestive heart failure

               -  Myocardial infarction <6 months prior to enrollment

               -  History of clinically significant ventricular arrhythmia

               -  History of cardiomyopathy with left ventricular ejection fraction ≤20%

               -  Pre-treatment Fredericia-adjusted QTc (QTcF) of >500 msec, unless the patient is
                  thought to be an acceptable candidate for dasatinib after consultation with a
                  cardiologist (including, but not limited to situations in which QTcF is thought
                  not representative of true length of repolarization due to pre-existing bundle
                  branch block or ventricular pacing)

          -  Patients with active hepatitis B infection (as manifest by either detectable hepatitis
             B virus DNA by PCR and/or positivity for hepatitis B surface antigen) are ineligible

          -  Patients with active hepatitis C infection (as manifest by detectable hepatitis C
             virus RNA by PCR) are ineligible. Patients with detectable antibodies to hepatitis C
             virus will be screened by PCR for evidence of active infection.

          -  Patients with HIV infection are ineligible, unless on antiretroviral therapy with
             undetectable HIV RNA by PCR (using an assay with sensitivity to detect levels of ≥50
             copies/mL) and otherwise eligible in the determination of the investigator.

          -  Ongoing need for systemic T-cell suppressive therapy (e.g. corticosteroids,
             tacrolimus, cyclosporine for active autoimmune disease or prior solid organ
             transplantation)

          -  Concurrent active malignancies as defined by malignancies requiring any therapy other
             than expectant observation or hormonal therapy, with the exception of squamous and
             basal cell carcinoma of skin

          -  Uncontrolled systemic fungal, bacterial, viral or other infection

          -  History or presence of uncontrolled or clinically significant neurological disorders
             such as generalized seizure disorder or severe brain injury

          -  Any other issue which, in the opinion of the treating physician, would make the
             patient ineligible for the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:the proportion of evaluable patients with minimal residual disease (MRD)
Time Frame:1 year
Safety Issue:
Description:To determine the proportion of evaluable patients achieving MRD negativity by multiparameter flow cytometry and quantitative PCR of BCR-ABL transcripts

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Blinatumomab
  • Concurrent Oral Tyrosine Kinase Inhibitor
  • Chemotherapy-Sparing Induction
  • 19-343

Last Updated

March 31, 2020