Ibrutinib With Methotrexate and Temozolomide for Patients With Newly Diagnosed Primary CNS Lymphoma

NCT04514393 | Unknown Phase 2

• 1 other identifier: MIT
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of the study is to test the efficacy and tolerability of a combination treatment of methotrexate, ibrutinib, and temozolomide (MIT regimen) in treating patients who have newly-diagnosed primary CNS lymphoma.

Conditions

Primary Central Nervous System Lymphoma; PCNSL; Non Hodgkin Lymphoma

Keywords

PCNSL; Newly Diagnosed

Outcome Measures

Primary Outcomes (2)

• the overall response (complete response + partial response)，Investigator-Assessed

  The overall response rate (ORR) including complete response (CR), unconfirmed complete (CRu) and partial response (PR) according to the 2005 Response Criteria of the International Primary CNS Lymphoma Collaborative Group (IPCG)

  up to 24 months

• the toxicity profile of the ibrutinib/MTX/ temozolomide combination therapy

  All subjects who received at least one dose of MIT will be included in the safety analysis. Adverse events will be graded by the investigator according to the NCI-CTCAE Version 5.0. Treatment-emergent adverse events (TEAEs) will be summarised and tabulated according to the primary system organ class and preferred term. Type, incidence, severity, and seriousness of adverse events (AEs) including physical examination, safety laboratory parameters, vital signs, and so on will be analyzed.

  up to 24 months

Secondary Outcomes (4)

• Complete response (CR) rate

  up to 24 months

• Duration of response（DOR）

  up to 24 months

• Progression-free survival (PFS)

  1 year and 2 years

• overall survival (OS)

  1 year and 2 years

Other Outcomes (2)

• Describe the tumor mutation profile by NGS

  up to 24 months

• Relationship between prognostic and gene mutation in patients with PCNSL

  up to 24 months

Study Arms (1)

methotrexate, ibrutinib, and temozolomide (MIT regimen)

EXPERIMENTAL

Methotrexate will be given on day 1 of each 28-day cycle；Ibrutinib will be given day 1-28 of each 28-day cycle; Temozolomide will be given day 1-5 of each 28-day cycle. Methotrexate and Temozolomide are given for up to 4 cycles; Ibrutinib is continued until disease progression, intolerable toxicity, or death.

Drug: Methotrexate; Drug: Ibrutinib; Drug: Temozolomide

Interventions

Methotrexate DRUG

Intravenous methotrexate at 3.5g/m2 (standard hydration/leucovorin support) will be given on day 1 of all cycles，for up to 4 cycles.

Also known as: MTX

methotrexate, ibrutinib, and temozolomide (MIT regimen)

Ibrutinib DRUG

Oral ibrutinib will be given at a dose of 560 mg daily and will be continued daily after completion of methotrexate and temozolomide.Ibrutinib is continued until disease progression, intolerable toxicity or death.

Also known as: Imbruvica

methotrexate, ibrutinib, and temozolomide (MIT regimen)

Temozolomide DRUG

Oral temozolomide will be given at 150mg/m2 from day1 to day 5 every 4 of all cycles，for up to 4 cycles.

Also known as: TMZ

methotrexate, ibrutinib, and temozolomide (MIT regimen)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and woman who are 18 to 70 years of age on the day of consenting to the study.
• Histologically documented PCNSL
• ECOG performance status ≤ 2.
• Life expectancy of \> 3 months (in the opinion of the investigator).
• Adequate bone marrow and organ function shown by:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
• Platelets ≥ 75 x 10\^9/L and no platelet transfusion within the past 14 days prior to study registration
• Hemoglobin (Hgb) ≥ 8 g/dL and no red blood cell (RBC) transfusion within the past 14 days prior to study registration
• 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
• Lipase ≤ 1.5 x upper limit of normal
• Women of childbearing potential (WOCBP) and men must agree to use effective contraception when sexually active. This applies for the time period between signing of the informed consent form and 30 days (for WOCBP) and 90 days (for men) after the last administration of study treatment. A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include but are not limited to hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for continuous 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy.
• The investigator or a designated associate is requested to advise the patient how to achieve highly effective birth control (failure rate of less than 1%), e.g. intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner and sexual abstinence

You may not qualify if:

• Patients eligible for this study must NOT MEET ANY of the following criteria:
• Active concurrent malignancy requiring active therapy
• Excluded medical conditions:
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure (New York Heart Association \> Class 2), unstable angina, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
• Uncontrolled hypertension despite optimal medical management (per investigators assessment)
• 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 is known to have an uncontrolled active systemic infection (\>CTCAE grade 2) and recent infection requiring intravenous anti-infective treatment that was completed ≤14 days before the first dose of study drug
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident, deep vein thrombosis or pulmonary embolism within 3 months before the start of study treatment
• Non-healing wound, ulcer or bone fracture
• Known bleeding diathesis (eg, von Willebrands disease) or hemophilia
• Known history of infection with human immunodeficiency virus (HIV) or active stage of infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) as determined by serologic tests, or any uncontrolled active systemic infection
• 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
• Unable to swallow capsules or disease significantly affecting gastrointestinal function, such as malabsorption syndrome, resection of the stomach or small bowel, or complete bowel obstruction
• Any life-threatening illness, medical condition including uncontrolled diabetes mellitus (DM), uncontrolled hypertension or organ system dysfunction that, in the opinion of the investigator, could compromise the subjects safety or put the study outcomes at undue risk
• Lactating or pregnant

Sponsors & Collaborators

• Huiqiang Huang: lead
• Guangdong 999 Brain Hospital: collaborator
• Nanfang Hospital, Southern Medical University: collaborator
• Xian-Janssen Pharmaceutical Ltd.: collaborator

Study Sites (3)

Department of Hematology Nanfang Hospital, The Southern Medical University

Guandong, Guangdong, 510515, China

RECRUITING

Department of Medical Oncology, Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Guangdong 999 Brain Hospital

Guangzhou, Guangdong, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

Methotrexate; ibrutinib; Temozolomide

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Huiqiang Huang, Professor

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Huiqiang Huang, Professor

CONTACT

+86 020 87343350; huanghq@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: professor

Model Details: Single Group Assignment

Study Record Dates

• First Submitted: August 11, 2020
• First Posted: August 14, 2020
• Study Start: October 10, 2020
• Primary Completion: September 1, 2022
• Study Completion: June 1, 2024
• Last Updated: April 7, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)