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

• ClinicalTrials.gov Identifier: NCT03569995
• Recruitment Status: Recruiting
• First Posted: June 26, 2018
• Last Update Posted: October 22, 2020
• Sponsor: Won Seog Kim
• Collaborator: Celltrion
• Information provided by (Responsible Party): Won Seog Kim, Samsung Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Primary CNS Lymphoma	Drug: Rituximab; Drug: Methotrexate; Drug: Cytarabine Injection	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 35 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment

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

• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Combination of Rituximab and Methotrexate Followed by Rituximab and Cytarabine in Elderly Patients With Primary CNS Lymphoma
• Actual Study Start Date: November 30, 2018
• Estimated Primary Completion Date: June 2024
• Estimated Study Completion Date: June 2025

Arms and Interventions

Arm

Intervention/treatment

Experimental: Induction+Consolidation chemotherapy; [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

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); Other Name: Truxima Inj; Drug: 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; Other Name: Methotrexate Inj; Drug: 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; Other Name: Cytarabine

Outcome Measures

Primary Outcome Measures :

1. 2-year progression free survival rate [ Time Frame: 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 ]
   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.

Secondary Outcome Measures :

1. progression free survival [ Time Frame: 2 years from the date of consent to the date of Progress disease f / u. ]
   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. overall survival [ Time Frame: Time between the start of treatment and the date of death.assessed up to 5 years] ]
   It measures the time from start of treatment to death.
3. Frequency of Adverse events classified by each criterion by CTCAE v4.0 [ Time Frame: from the date of informed consent signature to 31 days after last drug administration. ]
   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.
4. time to treatment failure [ Time Frame: Within 3 years ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 60 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Contacts

Contact: Wonseog Kim, M.D; 82-3410-6548; wonseog.kim@samsung.com

Contact: Seokjin Kim, M.D; 82-3410-1766; seokjin88.kim@samsung.com

Locations

Korea, Republic of

Samsung Medical Center; Recruiting

Seoul, Gangnam-gu,, Korea, Republic of, 06351

Contact: Kaeun Park, CRA 82-70-7014-4162 kaeun.park@samsung.com

Sponsors and Collaborators

Won Seog Kim

Celltrion

Investigators

• Principal Investigator: Wonseog Kim, M.D; Samsung Medical Center

More Information

• Responsible Party: Won Seog Kim, Clinical Professor, Samsung Medical Center
• ClinicalTrials.gov Identifier: NCT03569995
• Other Study ID Numbers: 2017-12-103
• First Posted: June 26, 2018
• Last Update Posted: October 22, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Cytarabine; Rituximab; Methotrexate; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Dermatologic Agents; Enzyme Inhibitors; Folic Acid Antagonists; Immunosuppressive Agents; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Anti-Infective Agents