Clinical Trials /

Ibrutinib and Blinatumomab in Treating Patients With Relapsed or Refractory B Acute Lymphoblastic Leukemia

NCT02997761

Description:

This phase II trial studies how well ibrutinib and blinatumomab work in treating patients with B acute lymphoblastic leukemia that has come back or is not responding to treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as blinatumomab, may interfere with the ability of cancer cells to grow and spread. Giving ibrutinib and blinatumomab may work better in treating patients with relapsed or refractory B acute lymphoblastic leukemia.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ibrutinib and Blinatumomab in Treating Patients With Relapsed or Refractory B Acute Lymphoblastic Leukemia
  • Official Title: A Phase 2 Study of Ibrutinib and Blinatumomab in Relapsed and Refractory B-Cell Acute Lymphoblastic Leukemia

Clinical Trial IDs

  • ORG STUDY ID: 945122
  • SECONDARY ID: UCDCC#266
  • SECONDARY ID: UCDCC#266
  • SECONDARY ID: P30CA093373
  • SECONDARY ID: NCI-2016-01882
  • NCT ID: NCT02997761

Conditions

  • Adult B Acute Lymphoblastic Leukemia
  • Philadelphia Chromosome Positive

Interventions

DrugSynonymsArms
BlinatumomabAnti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody, Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103, Blincyto, MEDI-538, MT-103Treatment (ibrutinib, blinatumomab)
IbrutinibBTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765Treatment (ibrutinib, blinatumomab)

Purpose

This phase II trial studies how well ibrutinib and blinatumomab work in treating patients with B acute lymphoblastic leukemia that has come back or is not responding to treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as blinatumomab, may interfere with the ability of cancer cells to grow and spread. Giving ibrutinib and blinatumomab may work better in treating patients with relapsed or refractory B acute lymphoblastic leukemia.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the efficacy of ibrutinib and blinatumomab in patients with relapsed or
      refractory B acute lymphoblastic leukemia (B-ALL) as measured by complete response (CR) rate.

      SECONDARY OBJECTIVES:

      I. To further examine the efficacy and safety of ibrutinib and blinatumomab in patients with
      relapsed or refractory B-ALL as measured by overall response rate (ORR, defined as CR plus CR
      with incomplete count recovery [CRi]), relapse free survival (RFS), overall survival (OS),
      minimal residual disease (MRD) response, proportion of patients bridged to allogeneic
      hematopoietic cell transplant (allo-HCT), and toxicity.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (ibrutinib, blinatumomab)ExperimentalINDUCTION THERAPY: Patients receive ibrutinib PO QD on days 1-49 of course 1 and days 1-42 of course 2, and blinatumomab IV on days 8-35 of course 1 and days 1-28 of course 2 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION THERAPY: Patients with CR/CRi after Induction Therapy receive ibrutinib PO QD on days 1-42 and blinatumomab IV on days 1-28. Treatment repeats every 42 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive ibrutinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Blinatumomab
  • Ibrutinib

Eligibility Criteria

        Inclusion Criteria:

          -  Pathologically confirmed diagnosis of relapsed or refractory B-cell acute
             lymphoblastic leukemia/lymphoma with measurable bone marrow lymphoblasts or
             biopsy-proven extramedullary site measurable by computed tomography (CT) or positron
             emission tomography (PET)/CT imaging; Philadelphia chromosome-positive (Ph+) B-ALL
             patients must have failed treatment with at least one second generation tyrosine
             kinase inhibitor; prior allo-HCT is allowed

          -  No hematologic parameters for inclusion; transfusion-dependent patients are eligible
             and platelet counts should be maintained greater than 10,000/mm^3 throughout cycles 1
             and 2

          -  Bilirubin less than or equal to 1.5 x upper limit of normal (ULN) (unless bilirubin
             rise is due to Gilbert's syndrome or B-ALL or non-hepatic origin)

          -  Serum aspartate transaminase (aspartate aminotransferase [AST]) or alanine
             transaminase (alanine aminotransferase [ALT]) less than or equal to 3 x ULN (unless
             due to B-ALL)

          -  Estimated creatinine clearance greater than or equal to 30 ml/min (Cockcroft-Gault) or
             serum creatinine less than or equal to 2 x ULN

          -  Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 x ULN and partial
             thromboplastin time (PTT) (activated partial thromboplastin time [aPTT]) =< 1.5 x ULN
             (unless B-ALL related)

          -  Karnofsky performance status (KPS) performance status of 60% or greater

          -  Ability to understand and willingness to sign an informed consent form

          -  Ability to adhere to the study visit schedule and other protocol requirements

          -  Female subjects who are of non-reproductive potential (i.e., post-menopausal by
             history - no menses for >= 1 year; OR history of hysterectomy; OR history of bilateral
             tubal ligation; OR history of bilateral oophorectomy); female subjects of childbearing
             potential must have a negative serum or urine pregnancy test within 72 hours prior to
             the first study drug administration

          -  Male and female subjects who agree to use both a highly effective methods of birth
             control (e.g., condoms, implants, injectables, combined oral contraceptives, some
             intrauterine devices [IUDs], complete abstinence, or sterilized partner) and a barrier
             method (e.g. condoms, vaginal ring, sponge, etc) during the period of therapy and for
             90 days after the last dose of study drug

          -  Eligibility of patients receiving any medications or substances known to affect or
             with the potential to affect the activity or pharmacokinetics of ibrutinib or
             blinatumomab will be determined following review of their case by the investigator

        Exclusion Criteria:

          -  Diagnosis of T acute lymphoblastic leukemia (T-ALL) or Burkitt's leukemia/lymphoma

          -  Patients with current evidence of active central nervous system (CNS) leukemia

          -  History of treatment with ibrutinib or blinatumomab

          -  Investigational therapy, chemotherapy, immunotherapy, radiotherapy, or systemic graft
             versus host disease (GVHD) therapy within two weeks or five half-lives (whichever is
             shorter); steroids, hydroxyurea and/or leukapheresis are allowed to control blast
             count prior to the first dose of study drug

          -  Prior allo-HCT less than three months from the time of enrollment

          -  Any active acute GVHD or chronic GVHD greater than grade 1

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to ibrutinib and blinatumomab or other agents used in this study

          -  Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug

          -  Recent culture-documented infection requiring intravenous antimicrobials that was
             completed =< 7 days before the first dose of study drug or any uncontrolled active
             systemic infection; fever of unknown origin is not an exclusion criterion, as this may
             be disease-related

          -  Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved
             to Common Terminology Criteria for Adverse Event (CTCAE, version [v]4.03), grade =< 2,
             or to the levels dictated in the inclusion/exclusion criteria with the exception of
             alopecia

          -  Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia

          -  History of stroke or intracranial hemorrhage within 6 months prior to enrollment

          -  Active infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or
             hepatitis B virus (HBV); subjects who are positive for hepatitis B core antibody,
             hepatitis B surface antigen, or hepatitis C antibody must have a negative polymerase
             chain reaction (PCR) result before enrollment; those who are PCR positive will be
             excluded; subjects with HIV must have a CD4 count at or above the institutional lower
             limit of normal and not taking prohibited CYP3A strong inhibitors

          -  Major surgery within 4 weeks of first dose of study drug

          -  Any life-threatening illness, medical condition, or organ system dysfunction,
             including but not limited to, ongoing or active infection, symptomatic congestive
             heart failure, unstable angina pectoris, cardiac arrhythmia, active autoimmune
             disorder, or psychiatric illness/social situations that, in the investigator's
             opinion, could compromise the subject's safety or put the study outcomes at undue
             risk; currently active, clinically significant cardiovascular disease, such as
             uncontrolled arrhythmia or class 3 or 4 congestive heart failure as defined by the New
             York Heart Association Functional Classification; or a history of myocardial
             infarction, unstable angina, or acute coronary syndrome within 6 months prior to
             enrollment

          -  History of other malignancies, except for malignancy surgically resected (or treated
             with other modalities) with curative intent, adequately treated in situ carcinoma of
             the breast or cervix uteri, basal cell carcinoma of the skin or localized squamous
             cell carcinoma of the skin; malignancy treated with curative intent with no known
             active disease present for >= 3 years

          -  Concomitant use of warfarin or other Vitamin K antagonists

          -  Subjects who received a strong cytochrome P 450 3A (CYP3A) inhibitor within 7 days
             prior to the first dose of ibrutinib or subjects who require continuous treatment with
             a strong CYP3A inhibitor

          -  Currently active, clinically significant hepatic impairment Child-Pugh class B or C
             according to the Child Pugh classification

          -  Breastfeeding or pregnant

          -  Participation in clinical trials with other investigational agents not included in
             this trial throughout the duration of this trial

          -  Unwilling or unable to participate in all required study evaluations and procedures or
             unable to understand the purpose and risks of the study and to provide a signed and
             dated informed consent form (ICF) and authorization to use protected health
             information (in accordance with national and local subject privacy regulations)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of CR
Time Frame:Up to 91 days
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Incidence of adverse events graded according to the National Cancer Institute CTCAE v4.03
Time Frame:Up to 6 months
Safety Issue:
Description:
Measure:MRD response
Time Frame:Up to 6 months
Safety Issue:
Description:
Measure:ORR defined as CR plus CRi assessed by disease-specific response criteria
Time Frame:Up to 6 months
Safety Issue:
Description:
Measure:OS
Time Frame:From the time of first study drug administration until the date of progression or death from any cause, assessed for up to 6 months
Safety Issue:
Description:
Measure:RFS
Time Frame:Time from CR/CRi until the date of progression or death from any cause, assessed for up to 6 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Brian Jonas

Last Updated

March 21, 2019