- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00153530
Whole Brain Irradiation in Primary Central Nervous System (CNS) Lymphoma (PCNSL)
Phase IV Study on the Role of Whole Brain Irradiation in Primary CNS Lymphoma (PCNSL) After High-dose Methotrexate
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Six 14-day cycles of high-dose MTX will be given at the beginning of the study. Randomization will be performed centrally at the study headquarters in UKBF Berlin already at study inclusion. Patients meeting all inclusion criteria will receive the first systemic treatment with 4 g/m2 MTX i.v. over 4 hours within 14 days. Dexamethasone in a dose of 3 x 8 mg/day orally for 10 days will additionally be given in the first cycle. This dexamethasone dose will be started 3 days before the first MTX application. Ten to 14 days after the 3rd and 6th MTX dose, the response to MTX therapy will be evaluated by MRI and a repeated CSF examination in the case of renewed CSF involvement. Assessment can also be made at any other time point if there is clinical deterioration. In all cases, the neuroradiological reference center (Department of Neuroradiology, University of Tübingen) will decide about the response to MTX therapy. MRI and CT scans should be sent to the neuroradiological reference center after HD MTX is terminated for central response evaluation. If complete remission is achieved after completing high-dose MTX therapy, patients will be treated with WBI (45 Gy in 1.5 Gy fractions) starting a minimum of 4 and a maximum of 7 weeks after the end of chemotherapy (arm A1) or WBI at first recurrence (arm A2). If primary therapy is not successful (partial remission, stable disease after the 6th cycle, progression at any time of MTX therapy), patients will receive WBI (45 Gy in 1.5 Gy fractions; arm B1) or high-dose AraC chemotherapy 3 g/m2 i.v. over 3 hours every 12 hours for 2 days (arm B2) according to the randomization. If high-dose MTX therapy leads to termination before the application of 6 cycles of MTX (see termination criteria) but allows further AraC therapy or WBI, further treatment is given in the non-CR arm according to the randomization. High-dose AraC therapy will be administered in four 3-week cycles. If complete remission occurs already after one or two cycles, only one additional cycle will be applied. Patients will not be crossed over into the B arms.
If there is a recurrence or progression after finishing a complete treatment arm, the patient can be treated with chemotherapy according to PCV protocol or WBI in the B2 arm. This decision is left up to the individual study center.
The G-PCNSL-SG-1 study is a prospective, controlled phase IV study with central randomization. Patients in both arms will be submitted to stratified randomization according to age (< 60; > 60) and center to minimize the effect of important therapy-related prognostic factors. The study is not blinded. Randomization will be performed centrally at study inclusion at the Institute of Medical Informatics, Biometry and Epidemiology, University Hospital Benjamin Franklin of the Free University of Berlin.
The planned study duration is 7 years - 4 years in the recruitment phase with a subsequent 3-year follow-up period and a 6-month evaluation phase. For an individual patient, the treatment time in arm A1 is 12 weeks for 6 cycles of MTX therapy, followed by a 4-7-week resting period and then 6 weeks until the completion of WBI (arm A1). In arm A2, the patient is irradiated (a total of 6 weeks) only in the case of recurrence. Up to that point, the patient will be followed up in fixed intervals like those patients in A1 after WBI. In arm B, MTX therapy is immediately followed by 6 weeks of WBI (arm B1) or the maximal 3 months of AraC therapy. After completing the protocol of the planned therapy, all patients will be followed-up for at least three years.
Study Type
Enrollment (Anticipated)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
-
Berlin, Germany, 12200
- Charite Campus Benjamin Franklin
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically or cytologically/immunocytologically confirmed primary non-Hodgkin's lymphoma of the CNS. A central reference pathological report will be made on inclusion into the study (Prof. Dr. Pietsch, Reference Center for Brain Tumors of the German Society for Neuropathology and Neuroanatomy, Institute of Neuropathology of the Bonn University Hospital). Histological diagnosis is usually performed by preferential stereotactic biopsy of suspicious lesions in the brain or spinal cord. The diagnosis from cerebrospinal fluid (CSF) requires the detection of malignant lymphocytes according to cytological and immunocytological criteria. There should be no more than 2 weeks between establishing the diagnosis and inclusion in the study. The availability of the reference pathological report is not absolutely necessary for inclusion in the study and beginning therapy.
- Aged > 18 years
- Life expectancy of at least 2 months
- Adequate bone marrow reserve with a peripheral granulocyte count of > 1,500/µl and thrombocyte count of > 100,000/µl; bilirubin in the normal range; GOT of < three times the upper normal limit and adequate renal function with a creatinine clearance of > 50 ml/min and serum creatinine in the normal range.
- Written informed consent
- In women of child-bearing age, pregnancy is excluded, effective contraception is necessary, and women should not be breast feeding.
Exclusion Criteria:
- Manifestation of lymphoma outside of the CNS
- Severe diseases in other organs which would make performing intensive chemotherapy impossible; Karnofsky index > 50% due to previous diseases other than PCNSL. Karnofsky > 30 will be accepted only due to the PCNSL.
- Active infection
- HIV positivity
- Previous treatment of PCNSL other than with corticosteroids, antiepileptics or diuretics
- Previous radiotherapy of the brain
- Concomitant or previous malignant diseases in the last 5 years except for an adequately treated basal cell carcinoma or cervical carcinoma in situ
- Immunosuppression, concomitant immunosuppressive therapy, or organ transplantation
- Ongoing chemotherapy for another disease
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: 1
1 chemotherapy with radiotherapy
|
whole-brain irradiation
|
Experimental: 2
chemotherapy without radiotherapy
|
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
overall survival
Time Frame: 3 years
|
3 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
progression-free survival
Time Frame: 3 years
|
3 years
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Eckhard Thiel, MD, Charite Campus Benjamin Franklin
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Methotrexate
Other Study ID Numbers
- G-PCNSL-SG1
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Central Nervous System Lymphoma
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingRefractory Central Nervous System Lymphoma | Central Nervous System B-Cell Non-Hodgkin Lymphoma | Recurrent Central Nervous System LymphomaUnited States
-
James RubensteinIncyte CorporationRecruitingPrimary Central Nervous System Lymphoma | CNS Lymphoma | Secondary Central Nervous System LymphomaUnited States
-
Second Affiliated Hospital, School of Medicine,...Active, not recruitingPrimary Central Nervous System Lymphoma | Refractory Central Nervous System Lymphoma | Relapsed Primary Central Nervous System LymphomaChina
-
Memorial Sloan Kettering Cancer CenterBristol-Myers SquibbActive, not recruitingPrimary Central Nervous System Lymphoma (PCNSL)United States
-
Dana-Farber Cancer InstituteRecruitingRefractory Central Nervous System Lymphoma | Central Nervous System Lymphoma | Recurrent Central Nervous System LymphomaUnited States
-
Second Affiliated Hospital, School of Medicine,...First People's Hospital of Hangzhou; First Affiliated Hospital of Zhejiang... and other collaboratorsRecruitingPrimary Central Nervous System Hodgkin LymphomaChina
-
Norwegian University of Science and TechnologySt. Olavs HospitalCompletedLymphoma, Non-Hodgkin | Central Nervous System NeoplasmsNorway
-
Institut CurieNational Cancer Institute, FranceRecruitingLymphoma, Large B-Cell, Diffuse | Central Nervous System Neoplasms, PrimaryFrance
-
Ono Pharmaceutical Co. LtdRecruitingPrimary CNS Lymphoma | Refractory Primary Central Nervous System LymphomaUnited States
-
Vanderbilt-Ingram Cancer CenterBristol-Myers Squibb; National Cancer Institute (NCI)TerminatedRecurrent Diffuse Large B-Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Refractory Central Nervous System Lymphoma | Recurrent Central Nervous System LymphomaUnited States
Clinical Trials on methotrexate
-
University Hospital, MontpellierPfizer; Hôpital CochinCompletedRheumatoid ArthritisFrance, Monaco
-
Nicolaus Copernicus UniversityCompleted
-
Amneal Pharmaceuticals, LLCAccutest Research Laboratories (I) Pvt. Ltd.Unknown
-
Hee Young JuNot yet recruitingLymphoblastic Leukemia in Children
-
PfizerCompletedRheumatoid ArthritisUnited States, Mexico, Argentina, Chile, Croatia, Czech Republic, Hungary, Poland, Puerto Rico
-
PfizerCompletedRhematoid ArthritisSpain, United Kingdom, United States, Korea, Republic of, Poland, Israel, Australia, Taiwan, Thailand, South Africa, Bulgaria, Estonia, Latvia, Philippines, Canada, Romania, Russian Federation, Turkey, Mexico, Bosnia and Herzegovina and more
-
Cairo UniversityCompleted
-
Chugai Pharma TaiwanCompletedRheumatoid Arthritis (RA)Taiwan
-
CHA UniversityCompleted
-
Mitsubishi Tanabe Pharma CorporationCompleted