Study on Pembrolizumab for Recurrent Primary Central Nervous System Lymphoma (PCNSL)
Primary Purpose
Primary Central Nervous System Lymphoma
Status
Unknown status
Phase
Phase 2
Locations
Austria
Study Type
Interventional
Intervention
pembrolizumab
Sponsored by
About this trial
This is an interventional treatment trial for Primary Central Nervous System Lymphoma focused on measuring Central nervous system lymphoma, Pembrolizumab
Eligibility Criteria
Inclusion Criteria:
- Be willing and able to provide written informed consent/assent for the trial.
- Minimum of 18 years of age on day of signing informed consent.
- Histologically confirmed diagnosis of PCNSL (DLBCL) at initial diagnosis
- The patient has a Karnofsky performance status of at least 50%.
- Documented progression or recurrence in cranial MRI after prior MTX-based first-line therapy (with or without prior radiotherapy)
- Measurable disease in cranial MRI (lesion size >10x10mm)
- Has no diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment except for a maximum dose of 4 mg/day dexamethasone or equivalent doses of other corticosteroids or control of brain edema, which has been stable or decreased for at least 1 week prior to inclusion.
- Is not pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- Female patient of childbearing potential has a negative urine or serum pregnancy test within 24 hours of first pembrolizumab infusion. lf the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the patient to be eligible.
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
- The patient has a life expectancy of at least 3 months.
- The patient has a Karnofsky performance status of at least 50%.
- The patient demonstrates adequate organ function
- Patient is able to undergo Gadolinium-MRI
Exclusion Criteria:
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Concurrent administration of any other antitumor therapy except steroids
- Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Has active infection requiring systemic therapy.
- Known history of active TB (Bacillus Tuberculosis)
- Known history of, or any evidence of active, non-infectious pneumonitis.
Has received a live vaccine within 30 days of planned start of study therapy.
o Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
- Drug abuse or extensive use of alcohol.
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Positive human immunodeficiency virus (HIV) test and a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- History of allergy to study drug components and no history of severe hypersensitivity reaction to any monoclonal antibody.
- Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1.
- Has not recovered (i.e.Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Known hypersensitivity to pembrolizumab or any of its excipients.
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
- Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
- Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
Sites / Locations
- Dept of Internal MedicineRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single arm
Arm Description
pembrolizumab
Outcomes
Primary Outcome Measures
Response assessment
Response assessment will be performed according to modified IPCG response criteria on contrast-enhanced cranial MRI-scans
Secondary Outcome Measures
Clinical adverse events
clinical adverse Events will be assessed by CTCAE v4.0
Laboratory parameters
adverse events due to laboratory parameters will be assessed by CTCAE v4.0
Full Information
NCT ID
NCT02779101
First Posted
May 17, 2016
Last Updated
June 21, 2016
Sponsor
Prof. Dr. Matthias Preusser
1. Study Identification
Unique Protocol Identification Number
NCT02779101
Brief Title
Study on Pembrolizumab for Recurrent Primary Central Nervous System Lymphoma (PCNSL)
Official Title
Open-label Single Arm Phase II Study on Pembrolizumab for Recurrent Primary Central Nervous System Lymphoma (PCNSL)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2016
Overall Recruitment Status
Unknown status
Study Start Date
June 2016 (undefined)
Primary Completion Date
June 2018 (Anticipated)
Study Completion Date
June 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Prof. Dr. Matthias Preusser
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
In summary, there is a high medical need for patients suffering from recurrent/progressive PCNSL. Targeting the PD-1 pathway may represent a very promising novel approach for the treatment of these patients.
Detailed Description
The objective of this study are:
PRIMARY OBJECTIVES
To evaluate the Overall Response Rate (CR/PR) in patients treated with pembrolizumab for relapsed PCNSL after MTX-based first-line therapy
To evaluate the safety of pembrolizumab in subjects diagnosed with recurrent PCNSL
SECONDARY OBJECTIVES
To describe Best Overall Response categories (CR, PR, SD, PD) in patients treated with pembrolizumab for relapsed PCNSL after MTX-based first-line therapy
To describe individual duration of response over time
To assess progression-free survival in this patient population
To assess overall survival in this patient population
EXPLORATORY OBJECTIVES
To assess PD-L1 as a predictive marker for response to pembrolizumab
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Central Nervous System Lymphoma
Keywords
Central nervous system lymphoma, Pembrolizumab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Single arm
Arm Type
Experimental
Arm Description
pembrolizumab
Intervention Type
Drug
Intervention Name(s)
pembrolizumab
Intervention Description
Pembrolizumab 200 mg every 3 weeks
Primary Outcome Measure Information:
Title
Response assessment
Description
Response assessment will be performed according to modified IPCG response criteria on contrast-enhanced cranial MRI-scans
Time Frame
after 24 month
Secondary Outcome Measure Information:
Title
Clinical adverse events
Description
clinical adverse Events will be assessed by CTCAE v4.0
Time Frame
after 24 month
Title
Laboratory parameters
Description
adverse events due to laboratory parameters will be assessed by CTCAE v4.0
Time Frame
after 24 month
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Be willing and able to provide written informed consent/assent for the trial.
Minimum of 18 years of age on day of signing informed consent.
Histologically confirmed diagnosis of PCNSL (DLBCL) at initial diagnosis
The patient has a Karnofsky performance status of at least 50%.
Documented progression or recurrence in cranial MRI after prior MTX-based first-line therapy (with or without prior radiotherapy)
Measurable disease in cranial MRI (lesion size >10x10mm)
Has no diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment except for a maximum dose of 4 mg/day dexamethasone or equivalent doses of other corticosteroids or control of brain edema, which has been stable or decreased for at least 1 week prior to inclusion.
Is not pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
Female patient of childbearing potential has a negative urine or serum pregnancy test within 24 hours of first pembrolizumab infusion. lf the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the patient to be eligible.
Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
The patient has a life expectancy of at least 3 months.
The patient has a Karnofsky performance status of at least 50%.
The patient demonstrates adequate organ function
Patient is able to undergo Gadolinium-MRI
Exclusion Criteria:
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
Concurrent administration of any other antitumor therapy except steroids
Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
Has active infection requiring systemic therapy.
Known history of active TB (Bacillus Tuberculosis)
Known history of, or any evidence of active, non-infectious pneumonitis.
Has received a live vaccine within 30 days of planned start of study therapy.
o Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
Drug abuse or extensive use of alcohol.
Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
Positive human immunodeficiency virus (HIV) test and a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
History of allergy to study drug components and no history of severe hypersensitivity reaction to any monoclonal antibody.
Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1.
Has not recovered (i.e.Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
Known hypersensitivity to pembrolizumab or any of its excipients.
Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Matthias Preusser, MD
Phone
+43140400
Ext
44450
Email
matthias.preusser@meduniwien.ac.at
First Name & Middle Initial & Last Name or Official Title & Degree
Marika Rosner
Phone
+43140400
Ext
44450
Email
marika.rosner@meduniwien.ac.at
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthias Preusser, MD
Organizational Affiliation
MU Vienna, Dep. f. Internal medicine I, Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dept of Internal Medicine
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Individual Site Status
Recruiting
12. IPD Sharing Statement
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Study on Pembrolizumab for Recurrent Primary Central Nervous System Lymphoma (PCNSL)
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