Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Patients With Newly Diagnosed or Refractory/Recurrent Primary Central Nervous System Lymphoma (PCNSL) and Refractory/Recurrent Secondary Central Nervous System Lymphoma (SCNSL)

  • STATUS
    Recruiting
  • End date
    Dec 19, 2023
  • participants needed
    109
  • sponsor
    Memorial Sloan Kettering Cancer Center
Updated on 19 June 2022

Summary

The purpose of this study is to test any good or bad effects of the study drug called of ibrutinib (also known as Imbruvica™). At this stage of this trial, the study is investigating whether Ibrutinib can be incorporated into the established first-line chemotherapy regimen rituximab, methotrexate, vincristine, and procarbazine (R-VMP) in order to further refine the first-line induction therapy for PCNSL, as observed by a superior CRR (complete response rate) (ARM D RECRUITING ONLY)

Details
Condition Adult Patients With Newly Diagnosed or Relapsed or Refractory Primary Central Nervous System Lymphoma (PCNSL), Or Relapsed or Refractory Secondary Central Nervous System Lymphoma (SCNSL)
Treatment Ibrutinib, procarbazine, HD- Methotrexate (MTX), Rituximab + HD- Methotrexate (MTX)
Clinical Study IdentifierNCT02315326
SponsorMemorial Sloan Kettering Cancer Center
Last Modified on19 June 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Participants must be able to understand and be willing to sign a written informed
Men and woman who are at least 18 years of age on the day of consenting to the study
consent document
Histologically or cystologically documented PCNSL or histologically documented
systemic diffuse large B-cell lymphoma (DLBCL)
Patients must have relapsed/refractory PCNSL or relapsed/refractory SCNSL (Arm A, B
Participants must have an ECOG performance status of 0, 1, or 2
C) or newly diagnosed PCNSL (Arm D)
Participants must have adequate bone marrow and organ function shown by
All patients need to have received at least one prior CNS directed therapy. There is
no restriction on the number of recurrences (Arm A, B , C only)
Patients with parenchymal lesions must have unequivocal evidence of disease
progression on imaging (MRI of the brain or head CT) 21 days prior to study
registration. For patients with leptomeningeal disease only, CSF cytology must
document lymphoma cells and/or imaging findings consistent with CSF disease 21 days
prior to study registration (at the discretion of the investigator) (Arm A, B , C
only)
Absolute neutrophil count (ANC) ≥ 0.75 x 109/L
Patients must be able to tolerate MRI/CT scans
Platelets ≥ 75 x 109/L and no platelet transfusion within the past 21 days prior
Patients must be able to tolerate lumbar puncture and/or Ommaya taps
to study registration
Hemoglobin (Hgb) ≥ 8 g/dL and no red blood cell (RBC) transfusion within the past
days prior to study registration
Arm D: PCNSL patients without one prior CNS directed treatment
International Normalized Ratio (INR) ≤ 1.5 and PTT (aPTT) ≤ 1.5 times the upper
limit of normal
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the
upper limit of normal
Serum bilirubin ≤ 1.5 times the upper limit of normal; or total bilirubin ≤ 3
times the upper limit of normal with direct bilirubin within the normal range in
patients with well documented Gilbert Syndrome
Serum creatinine ≤ 2 times the upper limit of normal
Arm C: calculated creatinine clearance(CrCl) > 50ml/min using the Cockcroft-Gault
equation (Men: CrCl (min/ml) = (140-age) X (actual weight in kg) / 72 X serum
creatinine (mg/dL); Women: CrCl (ml/min) = (140-age) X (actual weight in kg) X
85 / 72 X serum creatinine (mg/dL))
Woman of reproductive potential must agree to use highly effective methods of birth
control during the period of therapy and for 30 days after the last dose of the study
drug. Men who are sexually active must agree to use highly effective contraception
during the period of therapy and for 3 months after the last dose
Female subjects of childbearing potential must have a negative plasma pregnancy test
upon study entry. See section on Pregnancy and Reproduction
Participants must have recovered to grade 1 toxicity from prior therapy (Arm A, B , C
only)
Participates must be able to submit 20 unstained formalin-fixed, paraffin-embedded
(FFPE) slides from the initial tissue diagnosis prior to study registration for
confirmation of diagnosis and correlative studies Arm C1 and C2: SCNSL patients do not
require one prior CNS directed treatment. Newly diagnosed SCNSL patients are eligible
as long as their systemic disease has been treated and does not require any active
treatment

Exclusion Criteria

Patients with SCNSL actively receiving treatment for extra-CNS disease are excluded
Patient has an active concurrent malignancy requiring active therapy
Patient has a known bleeding diathesis (e.g. von Willebrand's disease) or hemophilia
Patient is known to have human immunodeficiency virus (HIV) infection
Patient is known to have an uncontrolled active systemic infection
Arm C and D: Patients with a methotrexate allergies are excluded
Patient is concurrently using other approved or investigational antineoplastic agents
Investigational supportive agents are permitted
Patient has received chemotherapy, monoclonal antibodies or targeted anticancer
therapy ≤ 4 weeks or 5 half-lives, whichever is shorter, or 6 weeks for nitrosurea, or
mitomycin-C prior to starting the study drug, or the patient has not recovered from
the side effects of such therapy Patient has received external beam radiation therapy
to the CNSwithin 21 days of the first dose of the study drug
Patient requires more than 8 mg of dexamethasone daily or the equivalent therapy (Arm
A, B , C only)
The patient has been treated with radio- or toxin-immunoconjugates within 70 days of
the first dose of the study drug
Patient has previously taken is allergic to components of the study drug. For Arms A
and B only: Patient has previously taken ibrutinib
Patient is using warfarin or any other Coumadin-derivative anticoagulant or vitamin K
antagonists. Patients must be off warfarin-derivative anticoagulants for at least
seven days prior to starting the study drug. Low molecular weight heparin is allowed
Patients with congenital bleeding diathesis are excluded
Patient is taking a drug known to be a moderate and strong inhibitor or inducers of
the P450 isoenzyme CYP3A. Participants must be off P450/CYP3A inhibitors and inducers
for at least two weeks prior to starting the study drug
Patient is using systemic immunosuppressant therapy, including cyclosporine A
tacrolimus, sirolimus, and other such medications, or chronic administration of > 5
mg/day or prednisone or the equivalent. Participants must be off of immunosuppressant
therapy for at least 28 days prior to the first dose of the study drug
Patient has significant abnormalities on screening electrocardiogram (EKG) and active
and significant cardiovascular disease such as uncontrolled or symptomatic
arrhythmias, congestive heart failure, hypertension, valvular disease, pericarditis
or myocardial infarction within 6 months of screening
Patient is known to have a history of active or chronic infection with hepatitis C
virus (HCV) or hepatitis B virus (HBV) as determined by serologic tests
Patient underwent major systemic surgery ≤ 2 weeks prior to starting the trial
treatment or who has not recovered from the side effects of such surgery, or who plan
to have surgery within 2 weeks of the first dose of the study drug therapy (Arm A, B
C only)
Patient is unable to swallow capsules or has a disease or condition significantly
affecting gastrointestinal function, such as malabsorption syndrome, resection of the
stomach or small bowel, or complete bowel obstruction
Patient has poorly controlled diabetes mellitus with a glycosylated hemoglobin >8% or
poorly controlled steroid-induced diabetes mellitus with a glycosylated hemoglobin of
>8%
Patient has a life-threatening illness, medical condition, or organ system dysfunction
that, in the opinion of the investigator, could compromise the subject's safety or put
the study outcomes at undue risk
Women who are pregnant or nursing (lactating), where pregnancy is defined as a state
of a female after conception until the termination of gestation, confirmed by a
positive serum hCG laboratory test of > 5 mIU/mL (See section on Pregnancy and
Reproduction)
Patient has undergone prior allogenic stem cell transplant (autologous stem cell
transplant is NOT an exclusion)
The patient is unwell or unable to participate in all required study evaluations and
procedures
Patient is 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 (PHI) in accordance with national and local subject privacy regulations. A
legal representative can consent on behalf of a patient who is able to understand the
purpose and risk of the study but not able to provide a signature on the ICF and
authorization to use PHI due to neurologic deficits (e.g. motor or language deficits)
(Arm A, B , C only)
Arm D: Patients with pre-existing peripheral motor or sensory neuropathy ≥ grade 3 (CTCAE
0)
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