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

Primary Purpose

Primary CNS Lymphoma

Status

Recruiting

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Rituximab

Methotrexate

Cytarabine Injection

About this trial

This is an interventional treatment trial for Primary CNS Lymphoma

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Histologically proven diagnosis of B-cell non-Hodgkin's lymphoma, exclusively localized in the central nervous system, cranial nerves, and/or eyes
No previous treatment; A tumorectomy on diagnostic purpose and/or use of glucocorticoids is allowed
Measurable lesion(s)
Age ≥ 60 years
Unfit patients for high-dose chemotherapy followed by autologous stem cell transplantation
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
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.
Written informed consent
ECOG performance scale 0, 1 or 2
Life expectancy > 3 months

Exclusion Criteria:

T-cell or NK/T cell lymphoma
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
Young and fit patients who are suitable for high-dose chemotherapy followed by autologous stem cell transplantation
Prior radiation therapy on target CNS lesion(s)
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
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
Known hypersensitivity to the investigational agent(s)

Sites / Locations

Samsung Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Induction+Consolidation chemotherapy

Arm 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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

overall survival

It measures the time from start of treatment to death.

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.

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.

Full Information

NCT ID

NCT03569995

First Posted

May 7, 2018

Last Updated

October 19, 2020

Sponsor

Won Seog Kim

Collaborators

Celltrion

1. Study Identification

Unique Protocol Identification Number

NCT03569995

Brief Title

[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

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Recruiting

Study Start Date

November 30, 2018 (Actual)

Primary Completion Date

June 2024 (Anticipated)

Study Completion Date

June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Won Seog Kim

Collaborators

Celltrion

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Primary CNS Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

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)

Allocation

N/A

Enrollment

35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Induction+Consolidation chemotherapy

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Rituximab

Other Intervention Name(s)

Truxima Inj

Intervention Description

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)

Intervention Type

Drug

Intervention Name(s)

Methotrexate

Other Intervention Name(s)

Methotrexate Inj

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Cytarabine Injection

Other Intervention Name(s)

Cytarabine

Intervention Description

3000 mg/m2 + 5%DW 200 mL IVF over 2 hrs steroid eye drop 0.1%, 2 drops q 6hrs, on days 1-9

Primary Outcome Measure Information:

Title

2-year progression free survival rate

Description

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.

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

Secondary Outcome Measure Information:

Title

progression free survival

Description

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.

Time Frame

2 years from the date of consent to the date of Progress disease f / u.

Title

overall survival

Description

It measures the time from start of treatment to death.

Time Frame

Time between the start of treatment and the date of death.assessed up to 5 years]

Title

Frequency of Adverse events classified by each criterion by CTCAE v4.0

Description

Time Frame

from the date of informed consent signature to 31 days after last drug administration.

Title

time to treatment failure

Description

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.

Time Frame

Within 3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically proven diagnosis of B-cell non-Hodgkin's lymphoma, exclusively localized in the central nervous system, cranial nerves, and/or eyes No previous treatment; A tumorectomy on diagnostic purpose and/or use of glucocorticoids is allowed Measurable lesion(s) Age ≥ 60 years Unfit patients for high-dose chemotherapy followed by autologous stem cell transplantation 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 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. Written informed consent ECOG performance scale 0, 1 or 2 Life expectancy > 3 months Exclusion Criteria: T-cell or NK/T cell lymphoma 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 Young and fit patients who are suitable for high-dose chemotherapy followed by autologous stem cell transplantation Prior radiation therapy on target CNS lesion(s) 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 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 Known hypersensitivity to the investigational agent(s)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Wonseog Kim, M.D

Phone

82-3410-6548

wonseog.kim@samsung.com

First Name & Middle Initial & Last Name or Official Title & Degree

Seokjin Kim, M.D

Phone

82-3410-1766

seokjin88.kim@samsung.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Wonseog Kim, M.D

Organizational Affiliation

Samsung Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Samsung Medical Center

City

Seoul

State/Province

Gangnam-gu,

ZIP/Postal Code

06351

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Kaeun Park, CRA

Phone

82-70-7014-4162

kaeun.park@samsung.com

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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