[CREMA]Combination of R-M Followed by R-A in Elderly Patients With Primary CNS Lymphoma

Won Seog Kim

Status and phase: Enrolling; Phase 2

Conditions: Primary CNS Lymphoma

Treatments: Drug: Cytarabine Injection; Drug: Rituximab; Drug: Methotrexate

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03569995

2017-12-103

Details and patient eligibility

About

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.

Full 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.

Enrollment: 35 estimated patients

Sex: All

Ages: 60+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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35 participants in 1 patient group

Induction+Consolidation chemotherapy

Experimental group

Description:

\[Induction phase\] ① After induction therapy (Rituximab-Methotrexate) 2 times, first evaluation * Complete, partial response or stable disease-\> next step * Progressive disease-\> eliminated ② After Induction therapy (Rituximab-Methotrexate) was added 3 times (total 5 times), 2nd evaluation * Complete response -\> consolidation therapy(Rituximab-Cytarabine) progress * Partial response or stable disease-\> Rituximab-Methotrexate 2 additional administrations * Progressive disease-\> eliminated ③ After Induction therapy (Rituximab-Methotrexate) was added twice (7 times in total), 3rd evaluation * Complete, partial response or stable disease-\> consolidation therapy(Rituximab-Cytarabine) * Progressive disease-\> eliminated

Treatment:

Drug: Methotrexate

Drug: Rituximab

Drug: Cytarabine Injection