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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
Must not have
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 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
Timeline
Screening 3 weeks
Treatment Varies
Follow Up 2 years
Awards & highlights
No Placebo-Only Group

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.
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.
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.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I've had recent cancer treatment or am still experiencing side effects.
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I am not currently using warfarin or similar blood thinners, or have stopped them for at least 7 days.
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I have a history of hepatitis B or C.
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I cannot swallow pills or have a serious gut problem affecting food absorption.
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I have a bleeding disorder such as von Willebrand's disease or hemophilia.
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I currently have an untreated or uncontrolled infection.
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My diabetes is not well-managed, with a HbA1c level over 8%.
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I have not had major surgery in the last 2 weeks and have no plans for surgery in the next 2 weeks.
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I am not currently receiving treatment for cancer that has spread outside my brain.
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I have severe nerve damage in my arms or legs.
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I am currently receiving treatment for another cancer.

Timeline

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

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
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 study objectives
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
9%
Insomnia
9%
Nasopharyngitis
9%
Hyperuricaemia
9%
Dyspnoea
9%
Haematoma
8%
Skin laceration
8%
Paraesthesia
7%
Dyspepsia
7%
Dry skin
7%
Cellulitis
7%
Conjunctivitis
7%
Skin infection
7%
Iron deficiency
7%
Anxiety
7%
Rhinitis
6%
Cataract
6%
Conjunctival haemorrhage
6%
Pruritus
6%
Hypokalaemia
6%
Syncope
6%
Vision blurred
6%
Abdominal pain
6%
Abdominal pain upper
6%
Nail infection
6%
Neck pain
6%
Purpura
6%
Asthenia
5%
Abdominal discomfort
5%
Chest pain
5%
Gingival bleeding
5%
Mouth ulceration
5%
Stomatitis
5%
Onychomycosis
5%
Rhinorrhoea
5%
Actinic keratosis
5%
Dermatitis
5%
Petechiae
5%
Influenza like illness
5%
COVID-19
5%
Gastroenteritis
5%
Tooth infection
5%
Limb injury
5%
Squamous cell carcinoma of skin
5%
Peripheral sensory neuropathy
5%
Rosacea
5%
Increased tendency to bruise
5%
Gout
5%
Basal cell carcinoma
5%
Folliculitis
5%
Oral herpes
5%
Gastrooesophageal reflux disease
4%
Retinal haemorrhage
4%
Angina pectoris
4%
Dry mouth
4%
Vertigo
4%
Haemorrhoids
4%
Ecchymosis
4%
Sepsis
4%
Chills
4%
Bronchitis
4%
Furuncle
4%
Joint injury
4%
Blood alkaline phosphatase increased
4%
Neutrophil count decreased
4%
Decreased appetite
4%
Joint swelling
4%
Depression
4%
Productive cough
4%
Skin ulcer
4%
Atrial flutter
4%
Hyperglycaemia
4%
Herpes zoster
3%
Abdominal distension
3%
Tinnitus
3%
Bladder transitional cell carcinoma
3%
Rotator cuff syndrome
3%
Sinus bradycardia
3%
Inguinal hernia
3%
Dysphagia
3%
Dry eye
3%
Dysuria
3%
Pollakiuria
3%
Hypoalbuminaemia
3%
Osteoporosis
3%
Erythema
3%
Acute myocardial infarction
3%
Malaise
3%
Cystitis
3%
Alanine aminotransferase increased
3%
Gamma-glutamyltransferase increased
3%
Musculoskeletal chest pain
3%
Seborrhoeic keratosis
3%
Neuralgia
3%
Benign prostatic hyperplasia
3%
Dyspnoea exertional
3%
Nasal congestion
3%
Pneumonitis
3%
Psoriasis
3%
Skin fissures
3%
Skin lesion
3%
Laryngitis
3%
Respiratory tract infection
3%
Bradycardia
3%
Acute kidney injury
3%
Wound infection
3%
Myalgia
3%
Skin toxicity
3%
Ear infection
3%
Paronychia
3%
Osteoarthritis
3%
Pericarditis
3%
Sciatica
3%
Ocular hyperaemia
3%
Nail disorder
2%
Pleural effusion
2%
Rectal haemorrhage
2%
Cholecystitis
2%
COVID-19 pneumonia
2%
Drug withdrawal syndrome
2%
Seasonal allergy
2%
Vitamin D deficiency
2%
Rash maculo-papular
2%
Hypotension
2%
Death
2%
Loss of consciousness
1%
Post procedural haemorrhage
1%
Laryngeal oedema
1%
Stress fracture
1%
Lumbar vertebral fracture
1%
Haemolytic anaemia
1%
Haemorrhagic disorder
1%
Viral infection
1%
Wound infection staphylococcal
1%
Cardiac failure acute
1%
Wheezing
1%
Colitis
1%
Oral blood blister
1%
Upper gastrointestinal haemorrhage
1%
Drug-induced liver injury
1%
Bacterial sepsis
1%
Brain abscess
1%
Device related infection
1%
Gastrointestinal infection
1%
Neurocryptococcosis
1%
Septic shock
1%
Streptococcal bacteraemia
1%
Femoral neck fracture
1%
Femur fracture
1%
Subdural haematoma
1%
Lethargy
1%
Subarachnoid haemorrhage
1%
Chronic kidney disease
1%
Urinary bladder haemorrhage
1%
Prostatitis
1%
Acute pulmonary oedema
1%
Hyponatraemia
1%
Muscular weakness
1%
Rash erythematous
1%
Hyperviscosity syndrome
1%
Melaena
1%
Clostridium difficile infection
1%
Post procedural sepsis
1%
Pyelonephritis
1%
Cerebrovascular accident
1%
Respiratory disorder
1%
Lymphadenopathy
1%
Streptococcal sepsis
1%
Amyloidosis
1%
Influenza
1%
Pneumonia viral
1%
Coronary artery disease
1%
Pericardial haemorrhage
1%
Urosepsis
1%
Spinal stenosis
100%
80%
60%
40%
20%
0%
Study treatment Arm
Arm A: Ibrutinib
Arm B: Zanubrutinib

Awards & Highlights

No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.

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 4
~2060

Find a Location

Who is running the clinical trial?

Pharmacyclics LLC.Industry Sponsor
113 Previous Clinical Trials
13,736 Total Patients Enrolled
Janssen Biotech, Inc.Industry Sponsor
29 Previous Clinical Trials
18,740 Total Patients Enrolled
Memorial Sloan Kettering Cancer CenterLead Sponsor
1,972 Previous Clinical Trials
597,619 Total Patients Enrolled
3 Trials studying Central Nervous System Lymphoma
128 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
~18 spots leftby Dec 2026
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