Clinical trial NCT03569995: [CREMA]Combination of R-M Followed by R-A in Elderly Patients With Primary CNS Lymphoma
Official title: Combination of Rituximab and Methotrexate Followed by Rituximab and Cytarabine in Elderly Patients With Primary CNS Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Primary CNS Lymphoma
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
Collaborators: name: Celltrion
First posted: 2018-06-26
Enrollment: 35
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: \[Induction phase\]

① After induction therapy (R-M) 2 times, first evaluation

* Complete, partial response or stable disease-\> next step
* Progressive disease-\> eliminated

  ② After Induction therapy (R-M) was added 3 times (total 5 times), 2nd evaluation
* Complete response -\> consolidation therapy progress
* Partial response or stable disease-\> R-M 2 additional administrations
* Progressive disease-\> eliminated

  ③ After Induction therapy (R-M) was added twice (7 times in total), 3rd evaluation
* Complete, partial response or stable disease-\> consolidation therapy
* Progressive disease-\> eliminated
Primary purpose: TREATMENT

Brief summary: This study was conducted to evaluate the 2-year progression free survival rate of elderly patients with primary CNS lymphoma followed by combination of rituximab and methotrexate followed by rituximab and cytarabine.

Detailed description: As described, standard therapy for patients with primary CNS lymphoma is not based on a high level of evidence yet, and studies in elderly patients with this disease are very limited. Based on the Korea National Cancer Incidence Database, it is estimated that about 100 \~ 150 cases of primary central nervous system lymphoma are diagnosed per year in Korea, but there is no analysis through prospective studies. As described previously, MTX monotherapy in elderly patients is relatively safe and does not reduce clinical utility. Although the autologous therapy may consider autologous stem cell transplantation, it is difficult to apply in elderly patients. Brain radiation therapy is not a primary consideration because it may cause neurological sequelae, especially in elderly patients. High-dose cytarabine is a safely administered drug that has been used extensively in clinical studies involving the treatment of elderly patients.Rituximab has not been studied prospectively for medications, doses, and intervals that are expected to play a role in patients with primary CNS lymphoma, as described above, and may be caused by reducing the number of cytotoxic anticancer drugs in elderly patients And to reduce the treatment effect.

Therefore, the authors propose a two-phase study in which R-A induction therapy is performed after R-M induction therapy in elderly patients with primary CNS lymphoma.

Eligibility criteria: Inclusion Criteria:

1. Histologically proven diagnosis of B-cell non-Hodgkin's lymphoma, exclusively localized in the central nervous system, cranial nerves, and/or eyes
2. No previous treatment; A tumorectomy on diagnostic purpose and/or use of glucocorticoids is allowed
3. Measurable lesion(s)
4. Age ≥ 60 years
5. Unfit patients for high-dose chemotherapy followed by autologous stem cell transplantation
6. Adequate organ functions

   * Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L
   * Platelets ≥ 50 x 109/L
   * Hemoglobin ≥ 8.0 g/dL
   * Serum Creatinine ≤ 1.5 x upper limit normal (ULN)
   * Serum Bilirubin ≤ 1.5 x ULN
   * AST and ALT ≤ 3 x ULN
7. Patients with adequately controlled HBV, HCV or HIV are allowed. In case of HBV (+), adequate anti-viral prophylaxis should be incorporated. In case of HIV (+), highly active anti-retroviral therapy should be incorporated.
8. Written informed consent
9. ECOG performance scale 0, 1 or 2
10. Life expectancy \> 3 months

Exclusion Criteria:

1. T-cell or NK/T cell lymphoma
2. Any evidence of systemic non-Hodgkin's lymphoma as demonstrated by computed tomography scan of the neck, chest, abdomen, and pelvis and bone marrow examinations
3. Young and fit patients who are suitable for high-dose chemotherapy followed by autologous stem cell transplantation
4. Prior radiation therapy on target CNS lesion(s)
5. Concurrent severe or uncontrolled medical conditions, laboratory abnormalities or psychiatric disorders that would preclude the participants in the study by the discretion of attending physicians
6. Metachronous malignancy other than adequately treated basal cell or squamous cell carcinoma of the skin, or CIN of uterine cervix, or prostate cancer that can be observed without treatment
7. Known hypersensitivity to the investigational agent(s)

Primary outcomes:
measure: 2-year progression free survival rate
timeFrame: the time between the date of treatment start and the date of death due to any cause or date of disease, assessed up to 24 months
Secondary outcomes:
measure: progression free survival
timeFrame: 2 years from the date of consent to the date of Progress disease f / u.
measure: overall survival
timeFrame: Time between the start of treatment and the date of death.assessed up to 5 years]
measure: Frequency of Adverse events classified by each criterion by CTCAE v4.0
timeFrame: from the date of informed consent signature to 31 days after last drug administration.
measure: time to treatment failure
timeFrame: Within 3 years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Gangnam-gu,
Study officials:
affiliation: Samsung Medical Center
name: Wonseog Kim, M.D
role: PRINCIPAL_INVESTIGATOR
References: