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

Last updated: May 28, 2024
Sponsor: Brian Jonas
Overall Status: Active - Recruiting

Phase

2

Condition

Leukemia

Treatment

Ibrutinib

Blinatumomab

Clinical Study ID

NCT02997761
945122
UCDCC#266
P30CA093373
NCI-2016-01882
  • Ages > 18
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Pathologically confirmed diagnosis of relapsed or refractory B-cell acutelymphoblastic leukemia/lymphoma with measurable bone marrow lymphoblasts orbiopsy-proven extramedullary site measurable by computed tomography (CT) or positronemission tomography (PET)/CT imaging; Philadelphia chromosome-positive (Ph+) B-ALLpatients must have failed treatment with at least one second generation tyrosinekinase inhibitor; prior allo-HCT is allowed

  • No hematologic parameters for inclusion; transfusion-dependent patients are eligibleand 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 bilirubinrise is due to Gilbert's syndrome or B-ALL or non-hepatic origin)

  • Serum aspartate transaminase (aspartate aminotransferase [AST]) or alaninetransaminase (alanine aminotransferase [ALT]) less than or equal to 3 x ULN (unlessdue 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 partialthromboplastin time (PTT) (activated partial thromboplastin time [aPTT]) =< 1.5 xULN (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 byhistory - no menses for >= 1 year; OR history of hysterectomy; OR history ofbilateral tubal ligation; OR history of bilateral oophorectomy); female subjects ofchildbearing potential must have a negative serum or urine pregnancy test within 72hours prior to the first study drug administration

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

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

Exclusion

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 systemicgraft versus host disease (GVHD) therapy within two weeks or five half-lives (whichever is shorter); steroids, hydroxyurea and/or leukapheresis are allowed tocontrol 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 orbiologic composition to ibrutinib and blinatumomab or other agents used in thisstudy

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

  • Recent culture-documented infection requiring intravenous antimicrobials that wascompleted =< 7 days before the first dose of study drug or any uncontrolled activesystemic infection; fever of unknown origin is not an exclusion criterion, as thismay be disease-related

  • Unresolved toxicities from prior anti-cancer therapy, defined as having not resolvedto 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 exceptionof 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) orhepatitis B virus (HBV); subjects who are positive for hepatitis B core antibody,hepatitis B surface antigen, or hepatitis C antibody must have a negative polymerasechain reaction (PCR) result before enrollment; those who are PCR positive will beexcluded; subjects with HIV must have a CD4 count at or above the institutionallower 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 congestiveheart failure, unstable angina pectoris, cardiac arrhythmia, active autoimmunedisorder, or psychiatric illness/social situations that, in the investigator'sopinion, could compromise the subject's safety or put the study outcomes at unduerisk; currently active, clinically significant cardiovascular disease, such asuncontrolled arrhythmia or class 3 or 4 congestive heart failure as defined by theNew York Heart Association Functional Classification; or a history of myocardialinfarction, unstable angina, or acute coronary syndrome within 6 months prior toenrollment

  • History of other malignancies, except for malignancy surgically resected (or treatedwith other modalities) with curative intent, adequately treated in situ carcinoma ofthe breast or cervix uteri, basal cell carcinoma of the skin or localized squamouscell carcinoma of the skin; malignancy treated with curative intent with no knownactive 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 daysprior to the first dose of ibrutinib or subjects who require continuous treatmentwith a strong CYP3A inhibitor

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

  • Breastfeeding or pregnant

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

  • Unwilling or unable to participate in all required study evaluations and proceduresor unable to understand the purpose and risks of the study and to provide a signedand dated informed consent form (ICF) and authorization to use protected healthinformation (in accordance with national and local subject privacy regulations)

Study Design

Total Participants: 20
Treatment Group(s): 2
Primary Treatment: Ibrutinib
Phase: 2
Study Start date:
June 27, 2017
Estimated Completion Date:
September 30, 2025

Study 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.

Connect with a study center

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California 95817
    United States

    Active - Recruiting

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