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

Primary CNS Lymphoma Clinical Trial

Official title:

Combination of Rituximab and Methotrexate Followed by Rituximab and Cytarabine in Elderly Patients With Primary CNS Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03569995
• Other study ID #: 2017-12-103
• Status: Recruiting
• Phase: Phase 2
• Start date: November 30, 2018
• Est. completion date: June 2025

Study information

• Verified date: October 2020
• Source: Samsung Medical Center
• Contact: Wonseog Kim, M.D
• Phone: 82-3410-6548
• Email: wonseog.kim[@]samsung.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 35
• Est. completion date: June 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Lymphoma
• Primary CNS Lymphoma

Intervention

Drug:
• Rituximab
500 mg/m2 + 5%DW 500 mL IVF Begin with 50 mg/hr (increase by 50 mg/hr per 30 min until 400 mg/hr is reached)
• Methotrexate
500 mg/m2 + 5%DW 200 mL IV over 15 minutes 3000 mg/m2 + 5%DW 500 mL IVF over 3 hrs Concurrent hydration and subsequent leucovorin rescue is mandatory
• Cytarabine Injection
3000 mg/m2 + 5%DW 200 mL IVF over 2 hrs steroid eye drop 0.1%, 2 drops q 6hrs, on days 1-9

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul	Gangnam-gu,

Sponsors (2)

Lead Sponsor	Collaborator
Won Seog Kim	Celltrion

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	2-year progression free survival rate	From the end of the last patient's trial, the disease progression will be tracked for up to 2 years, and primary analysis and reporting will be conducted.	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	progression free survival	Means the period from the date of consent to the date of disease progression, the time of death, or the last time the disease has not progressed or has confirmed its survival.	2 years from the date of consent to the date of Progress disease f / u.
Secondary	overall survival	It measures the time from start of treatment to death.	Time between the start of treatment and the date of death.assessed up to 5 years]
Secondary	Frequency of Adverse events classified by each criterion by CTCAE v4.0	CTCAE v4 (Common Terminology Criteria for Adverse Events v4.0) In the present study, toxicities will be recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Event (CTCAE), version 4.0. Then, the collected Toxicity is classified by CTCAE term and calculated as%, and a lot of AE will be detected.	from the date of informed consent signature to 31 days after last drug administration.
Secondary	time to treatment failure	Means the period from the date of consent to the date of the onset of the disease or to the discontinuation of treatment for any reason.	Within 3 years