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BTK Inhibitor

Ibrutinib + Chemotherapy for CNS Lymphoma

Phase 1 & 2

Recruiting

Led By Christian Grommes, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Participants must have an ECOG performance status of 0, 1, or 2

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

Study Summary

This trial is testing whether ibrutinib, a study drug, can be used in conjunction with an established chemotherapy regimen to treat primary central nervous system lymphoma.

Who is the study for?

This trial is for adults with primary or secondary central nervous system lymphoma who have had at least one prior CNS therapy (except for some newly diagnosed cases). They must understand the study and consent, have a certain level of physical function, adequate organ function, agree to use effective birth control, and not be pregnant. Exclusions include uncontrolled infections, certain drug interactions, severe heart conditions, inability to swallow capsules, among others.Check my eligibility

What is being tested?

The trial tests Ibrutinib's effectiveness when added to an established chemotherapy regimen (rituximab + high-dose methotrexate + procarbazine) in patients with central nervous system lymphoma. It aims to improve complete response rates by refining first-line induction therapy.See study design

What are the potential side effects?

Potential side effects may include digestive issues due to chemotherapy drugs like procarbazine and methotrexate; infusion reactions from rituximab; bleeding risks associated with Ibrutinib; as well as general side effects such as fatigue and increased risk of infection.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My bilirubin levels are within the normal range, or slightly elevated due to Gilbert Syndrome.

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I am able to care for myself and perform daily activities.

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My platelet count is above 75 x 109/L and I haven't had a platelet transfusion in the last 3 weeks.

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I agree to use effective birth control during and after the study.

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I have primary CNS lymphoma and haven't had any CNS treatments before.

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My CNS lymphoma has returned after treatment or didn't respond to treatment, or I have newly diagnosed PCNSL.

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My hemoglobin is at least 8 g/dL and I haven't had a blood transfusion in the last 3 weeks.

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My kidney function is good based on a creatinine clearance test.

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My lymphoma is confirmed by lab tests.

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I can undergo spinal fluid tests.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

define the Maximum Tolerated Dose (MTD) of ibrutinib (phase I)

define the Maximum Tolerated Dose (MTD) of ibrutinib in combination with high-dose Methotrexate (HD-MTX)

progression free survival (phase II)

Secondary outcome measures

Duration of response

progression free survival

safety/tolerability of ibrutinib in patients by assessing the frequency and severity of adverse events

Side effects data

From 2022 Phase 3 trial • 201 Patients • NCT03053440

37%

Diarrhoea

32%

Upper respiratory tract infection

29%

Muscle spasms

28%

Contusion

24%

Arthralgia

24%

Hypertension

22%

Oedema peripheral

22%

Anaemia

21%

Epistaxis

20%

Cough

19%

Rash

19%

Fatigue

18%

Back pain

18%

Atrial fibrillation

17%

Urinary tract infection

16%

Neutropenia

16%

Thrombocytopenia

15%

Nausea

15%

Headache

15%

Vomiting

14%

Pneumonia

14%

Dizziness

13%

Haematuria

12%

Peripheral swelling

12%

Pyrexia

12%

Constipation

11%

Localised infection

10%

Pain in extremity

10%

Onychoclasis

10%

Fall

10%

Oropharyngeal pain

10%

Lower respiratory tract infection

10%

Sinusitis

10%

Palpitations

Nasopharyngitis

Hyperuricaemia

Insomnia

Dyspnoea

Haematoma

Skin laceration

Paraesthesia

Dry skin

Dyspepsia

Cellulitis

Conjunctivitis

Skin infection

Iron deficiency

Anxiety

Rhinitis

Cataract

Conjunctival haemorrhage

Pruritus

Hypokalaemia

Syncope

Vision blurred

Abdominal pain

Abdominal pain upper

Nail infection

Neck pain

Purpura

Asthenia

Actinic keratosis

Dermatitis

Stomatitis

Gingival bleeding

Rhinorrhoea

Petechiae

Mouth ulceration

Onychomycosis

Abdominal discomfort

Chest pain

Influenza like illness

COVID-19

Gastroenteritis

Tooth infection

Limb injury

Squamous cell carcinoma of skin

Peripheral sensory neuropathy

Rosacea

Increased tendency to bruise

Gout

Basal cell carcinoma

Folliculitis

Oral herpes

Gastrooesophageal reflux disease

Haemorrhoids

Vertigo

Ecchymosis

Sepsis

Angina pectoris

Retinal haemorrhage

Dry mouth

Chills

Bronchitis

Furuncle

Joint injury

Blood alkaline phosphatase increased

Neutrophil count decreased

Decreased appetite

Joint swelling

Depression

Productive cough

Skin ulcer

Atrial flutter

Hyperglycaemia

Herpes zoster

Tinnitus

Abdominal distension

Dysuria

Pollakiuria

Dry eye

Osteoporosis

Erythema

Bladder transitional cell carcinoma

Hypoalbuminaemia

Rotator cuff syndrome

Inguinal hernia

Acute myocardial infarction

Sinus bradycardia

Dysphagia

Malaise

Cystitis

Alanine aminotransferase increased

Gamma-glutamyltransferase increased

Musculoskeletal chest pain

Seborrhoeic keratosis

Neuralgia

Benign prostatic hyperplasia

Dyspnoea exertional

Nasal congestion

Pneumonitis

Psoriasis

Skin fissures

Skin lesion

Laryngitis

Respiratory tract infection

Bradycardia

Acute kidney injury

Wound infection

Myalgia

Skin toxicity

Ear infection

Paronychia

Osteoarthritis

Pericarditis

Sciatica

Ocular hyperaemia

Nail disorder

Rectal haemorrhage

Cholecystitis

COVID-19 pneumonia

Pleural effusion

Drug withdrawal syndrome

Seasonal allergy

Vitamin D deficiency

Rash maculo-papular

Hypotension

Death

Loss of consciousness

Haemolytic anaemia

Wheezing

Wound infection staphylococcal

Viral infection

Cardiac failure acute

Haemorrhagic disorder

Colitis

Oral blood blister

Upper gastrointestinal haemorrhage

Drug-induced liver injury

Bacterial sepsis

Brain abscess

Device related infection

Gastrointestinal infection

Neurocryptococcosis

Septic shock

Streptococcal bacteraemia

Femoral neck fracture

Femur fracture

Lumbar vertebral fracture

Post procedural haemorrhage

Stress fracture

Subdural haematoma

Lethargy

Subarachnoid haemorrhage

Chronic kidney disease

Urinary bladder haemorrhage

Prostatitis

Acute pulmonary oedema

Laryngeal oedema

Hyponatraemia

Muscular weakness

Rash erythematous

Hyperviscosity syndrome

Melaena

Clostridium difficile infection

Post procedural sepsis

Pyelonephritis

Cerebrovascular accident

Respiratory disorder

Lymphadenopathy

Streptococcal sepsis

Amyloidosis

Influenza

Pneumonia viral

Coronary artery disease

Pericardial haemorrhage

Urosepsis

Spinal stenosis

100%

80%

60%

40%

20%

Study treatment Arm

Arm A: Ibrutinib

Arm B: Zanubrutinib

Trial Design

4Treatment groups

Experimental Treatment

Group I: Arm D: Participants with refractory/recurrent PCNSL or refractory/recurrent SCNSLExperimental Treatment4 Interventions

THIS IS ONLY ARM RECRUITING In Arm D, patients will be treated with 4 cycles of therapy. Methotrexate (3.5 g/m2) will be given at Dday 1 and Dday 15 of each cycle. Rituximab (500 mg/m2) will be given at Dday 0 and Dday 15 of each cycle. Vincristine (1.4mg/m2) will be given at Dday 1 and 15 of cycle 1 and 2 only. Procarbazine (100mg/m2) will be given of Day 1 of each cycle. Ibrutinib will be dosed at 560 mg daily. Arm D will have a safety lead-in of 6 patients. If more than 1 of 6 subjects develop a dose limiting toxicity (DLT) within the first 28 days of therapy (cycle 1), ibrutinib will be reduced to 420 mg daily dosing, and 6 additional patients will be enrolled. If more than 1 of 6 subjects develop a DLT, additional enrollment will be stopped.

Group II: Arm C: Participants with refractory/recurrent PCNSL or refractory/recurrent SCNSLExperimental Treatment3 Interventions

Arm C will investigate the MTD of ibrutinib in combination with HD-MTX and to determine the safety and tolerability of the ibrutinib/HD-MTX combination regimen in PCNSL and SCNSL patients. To minimize drug-drug interaction between HD-MTX and Ibrutinib, Ibrutinib will not be administered concurrently with HD-MTX.

Group III: Arm B: Participants with refractory/recurrent PCNSL or refractory/recurrent SCNSLExperimental Treatment3 Interventions

The defined MTD from Arm A will then be used in an expansion cohort to further assess toxicity and clinical activity

Group IV: Arm A: Participants with refractory/recurrent PCNSL or refractory/recurrent SCNSLExperimental Treatment3 Interventions

This is an open-label, non-randomized, single center, dose escalation, phase I/II study to establish the maximum-tolerated dose (MTD) of ibrutinib as a single agent in patients with refractory/recurrent PCNSL or refractory/recurrent SCNSL (Arm A).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ibrutinib

2014

Completed Phase 3

~1880

0 / 10Eligibility criteria met

Find a Location

Who is running the clinical trial?

Pharmacyclics LLC.Industry Sponsor

113 Previous Clinical Trials

13,706 Total Patients Enrolled

Janssen Biotech, Inc.Industry Sponsor

29 Previous Clinical Trials

18,700 Total Patients Enrolled

Memorial Sloan Kettering Cancer CenterLead Sponsor

1,936 Previous Clinical Trials

588,789 Total Patients Enrolled

4 Trials studying Central Nervous System Lymphoma

161 Patients Enrolled for Central Nervous System Lymphoma

Media Library

Ibrutinib (BTK Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT02315326 — Phase 1 & 2

$Central Nervous System Lymphoma Research Study Groups: Arm D: Participants with refractory/recurrent PCNSL or refractory/recurrent SCNSL, Arm C: Participants with refractory/recurrent PCNSL or refractory/recurrent SCNSL, Arm A: Participants with refractory/recurrent PCNSL or refractory/recurrent SCNSL, Arm B: Participants with refractory/recurrent PCNSL or refractory/recurrent SCNSL$

Central Nervous System Lymphoma Clinical Trial 2023: Ibrutinib Highlights & Side Effects. Trial Name: NCT02315326 — Phase 1 & 2

Ibrutinib (BTK Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT02315326 — Phase 1 & 2

Frequently Asked Questions

These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

How many participants are enrolled in this trial?

"Affirmative. The clinicaltrials.gov website reveals that this medical trial is presently looking for applicants; it was first uploaded on December 1st 2014 and the page has been revised most recently on June 6th 2022. 109 individuals are being sought after from 7 distinct healthcare facilities."

Answered by AI

Is there still availability to join this research program?

"Confirmed. According to information hosted on the clinicaltrials.gov website, this medical trial is actively enrolling patients. The listing was first published in December 2014 and last updated June 2022."

Answered by AI

How many medical institutions have implemented this research project?

"The list of locations taking part in the clinical trial consists of Memorial Sloan Kettering Nassau (Uniondale), Memorial Sloan Kettering Monmouth(Middletown) and MemorialSloanKetteringCancerCenterNewYork, among other 7 sites."

Answered by AI

What conditions can Ibrutinib be deployed to alleviate?

"Ibrutinib is regularly prescribed to those suffering from stage III Hodgkin's disease. It can also potentially help patients with bladder cancer, diffuse large B-cell lymphoma (DLBCL), and meningeal leukemia manage the growth of their tumours."

Answered by AI

To what extent has Ibrutinib been explored in other scientific research?

"In 1993, ibrutinib was first researched at the National Institutes of Health Clinical Center in Rockville Pike. Since then, there have been 1455 completed trials and a further 700 are still active. The majority of these is conducted from Uniondale, New jersey."

Answered by AI

Recent research and studies

European Journal of Nuclear Medicine and Molecular ImagingJournal

Prognostic Value of [18F]FDG PET/CT in Patients with CNS Lymphoma Receiving Ibrutinib-based Therapies

Krebs, Simone, Audrey Mauguen, Onur Yildirim, Vaios Hatzoglou, Jasmine H. Francis, Lauren R. Schaff, Ingo K. Mellinghoff, Heiko Schöder, and Christian Grommes. 2021. “Prognostic Value of [18F]FDG PET/CT in Patients with CNS Lymphoma Receiving Ibrutinib-based Therapies”. European Journal of Nuclear Medicine and Molecular Imaging. Springer Science and Business Media LLC. doi:10.1007/s00259-021-05386-0.

BloodJournal

Phase 1b Trial of an Ibrutinib-based Combination Therapy in Recurrent/refractory CNS Lymphoma

Grommes, Christian, Sarah S. Tang, Julia Wolfe, Thomas J. Kaley, Mariza Daras, Elena I. Pentsova, Anna F. Piotrowski, et al.. 2019. “Phase 1b Trial of an Ibrutinib-based Combination Therapy in Recurrent/refractory CNS Lymphoma”. Blood. American Society of Hematology. doi:10.1182/blood-2018-09-875732.

European Journal of Nuclear Medicine and Molecular ImagingJournal

Prognostic Value of [18F]FDG PET/CT in Patients with CNS Lymphoma Receiving Ibrutinib-based Therapies

clinicaltrials.govStudy

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)