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Phase IV Study on the Role of Whole Brain Irradiation in Primary CNS Lymphoma (PCNSL) After High-dose Methotrexate

Phase 4
18 Years
Not Enrolling
Central Nervous System Lymphoma

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Trial Information

Phase IV Study on the Role of Whole Brain Irradiation in Primary CNS Lymphoma (PCNSL) After High-dose Methotrexate

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.

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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

overall survival

Outcome Time Frame:

3 years

Principal Investigator

Eckhard Thiel, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Charite Campus Benjamin Franklin


Germany: Federal Institute for Drugs and Medical Devices

Study ID:




Start Date:

May 2000

Completion Date:

May 2009

Related Keywords:

  • Central Nervous System Lymphoma
  • primary central nervous system lymphoma
  • Lymphoma