Efficay and safety study of Nivolumab in subjects with Primary Central Nervous System Lymphoma (PCNSL) and Primary Testicular Lymphoma (PT
- Conditions
- Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL) and Relapsed/Refractory Primary Testicular Lymphoma (PTL)MedDRA version: 20.0Level: LLTClassification code 10036685Term: Primary central nervous system lymphomaSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10043302Term: Testicular cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-000894-19-FR
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 100
1. Signed Written Informed Consent
2. Target Population
a) Subject must be 18 years of age or older
b) Subjects with pathologically confirmed PCNSL or PTL who progressed after or did not respond to at least 1 line of systemic therapy
i) PCNSL prior therapy may include HD-MTX, HD-MTX-based regimen, high-dose cytarabine, radiation therapy alone as treatment or as part of consolidation therapy, high-dose therapy with autologous stem cell transplant as part of consolidation therapy, and/or intraocular MTX alone or as part of consolidation therapy
ii) PTL prior therapy may include chemo-immunotherapy (eg, CHOP-R or any other regimens), with/without prophylactic RT to contralateral testis or intrathecal chemotherapy
c) Measurable disease requirements on scans done within 28 days of first dose (14 days for MRI of the brain):
i) PCNSL subjects should have at least 1 measurable extranodal brain lesion with the longest diameter > 1.0 cm on Gd-enhanced MRI
ii) PTL subjects should have at least 1 measurable extranodal lesion with the longest diameter > 1.0 cm on fluorodeoxyglucose (FDG) PET/CT scan (or spiral CT/MRI in patients who cannot undergo FDG PET/CT)
d) Archived tumor block or unstained slides from biopsy. Histologically confirmed tissue will be required from the time of relapse or at the time of initial surgery.
e) Subjects must have a Karnofsky performance status of 70-100 (Appendix 2)
f) Subject re-enrollment: This study permits the re-enrollment of a subject that has discontinued the study as a pre-treatment failure (ie, subject has not been treated). If re-enrolled, the subject must be re-consented and assigned a new subject number by the IVRS.
g) Subjects with prior history of allogeneic transplant can participate if the transplant was performed at least 6 or more months before screening. If there is no prior history of Grade 2 + acute graft versus host disease (GVHD), no history of extensive or Grade 4 chronic GVHD, or no immunosuppressive therapy for a minimum of 4 weeks with no clinically apparent GVHD.
3. Physical and Laboratory Test Findings
Screening laboratory values must meet the following criteria (using Common Terminology Criteria for Adverse Events [CTCAE] v4.03):
a) Whole blood count (WBC) more or equal to 2000/uL
b) Neutrophils more or equal to 1500/uL
c) Platelets more or equal to 100x103/uL
d) Hemoglobin more or equal to 9.0 g/dL
e) Serum creatinine less or equal to 1.5x upper limit of normal (ULN) or calculated creatinine clearance > 50 mL/min (using the Cockcroft-Gault formula) Female creatinine clearance (CrCl) = (140 - age in years) x weight in kg x 0.85
72 x serum creatinine in mg/dL
Male CrCl = (140- age in years) x weight in kg x 1.00
72 x serum creatinine in mg/ dL
f) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less or equal to 3.0 x ULN
g) Total bilirubin (TBILI) less or equal to 1.5 x ULN (except subjects with Gilbert Syndrome who must have a total bilirubin level of < 3.0xULN)
4. Age and Reproductive Status
a) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study drug
b) Women must not be pregnant or breastfeeding
c) WOCBP must agree to follow instructions for method(s) of contraception for a period of 30 days (duration of ovulatory cycle) plus the time required for the investigational drug
1. Target Disease Exceptions
a) Intraocular PCNSL without evidence of brain disease
b) PCNSL patients who cannot undergo MRI with contrast assessments
c) PCNSL patients with systemic disease
2. Medical History and Concurrent Diseases
a) Subjects with an active, known, or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
b) Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. Dose of dexamethasone less or equal to 4 mg/day or equivalent for PCNSL or PTL with brain and/or spine lesions is allowed.
c) Subjects who have received chemotherapy within 3 weeks of study treatment (except: HD-MTX within 2 weeks of treatment permitted if serum MTX levels < 1 micoM and meets other lab criteria for inclusion), nitrosoureas within 6 weeks of treatment, therapeutic anti-cancer antibodies (such as rituximab) within 4 weeks, radio- or toxin immuneconjugates within 10 weeks of treatment.
d) Received any investigational agent within 28 days or 5 half-lives (whichever is shorter) prior to initiation of study treatment
e) Major surgery and/or radiotherapy within 14 days prior to initiation of study treatment
f) Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be performed at sites where mandated locally
g) Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast
h) Patients with serious or uncontrolled medical disorders
i) Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
3. Physical and Laboratory Test Findings
a) Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection, and/or detectable virus
4. Allergies and Adverse Drug Reaction
a) History of severe allergy or hypersensitivity to study drug components
5. Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject. Strict conditions apply and BMS approval is required.)
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method