## Protocol Section
### Identification Module
**NCT ID:** NCT04934579

**Brief Title:** Rituximab,Methotrexate and Lenalidomide in Newly Diagnosed Primary Central Nervous System Lymphoma

**Official Title:** Efficacy and Safety Study of Rituximab, Methotrexate and Lenalidomide Chemotherapy（R2-MTX） in Newly Diagnosed Primary Central Nervous System Lymphoma：a Single Arm, Multicenter, Phase 2 Study

#### Organization Study ID Info
**ID:** I2021001531
#### Organization
**Class:** OTHER
**Full Name:** Second Affiliated Hospital, School of Medicine, Zhejiang University
### Status Module
#### Completion Date
**Date:** 2022-11-15

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2022-11-23

**Type:** ACTUAL

**Last Update Submit Date:** 2022-11-18

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2022-10-15

**Type:** ACTUAL

#### Start Date
**Date:** 2020-01-01

**Type:** ACTUAL

**Status Verified Date:** 2022-11

#### Study First Post Date
**Date:** 2021-06-22
**Type:** ACTUAL
**Study First Submit Date:** 2021-06-14
**Study First Submit QC Date:** 2021-06-20
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Second Affiliated Hospital, School of Medicine, Zhejiang University

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** It is a single arm, multicenter, phase 2 study to explore the efficacy and safety study of R2-MTX chemotherapy（Lenalidomide, Rituximab and Methotrexate）as first-line regimens in the treatment of newly diagnosed primary central nervous system lymphoma. Objective response rate is the primary endpoint.

**Detailed Description:** This is a single arm, multicenter, phase 2 study designed to evaluate the efficacy and safety of rituximab, methotrexate and lenalidomide as first-line regimens in the treatment of newly primary central nervous system lymphoma. A total of 40 patients plan to participate in this study to receive a total 6 cycles of induction chemotherapy followed by 4 cycles of maintenance chemotherapy. Follow-ups should be taken up to the first 3 years. The primary endpoint is objective response rate (ORR) and secondary endpoint includes Progression free survival (PFS), overall survival (OS), and adverse events.

### Conditions Module

**Conditions:**

- Primary Central Nervous System Lymphoma

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 17

**Type:** ACTUAL

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Experimental arm will be treated with R2-MTX regimen(Lenalidomide plus Rituximab and Methotrexate) for 6 cycles as initiate induction.If the patients achieved complete remission（CR）or partial remission（PR）with additional whole-brain radiotherapy（WBRT）, they processed to R2 maintenance(Lenalidomide plus Rituximab) for 4 cycles.

**Intervention Names:**

- Drug: Rituximab

- Drug: Lenalidomide

- Drug: Methotrexate

**Label:** R2-MTX

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- R2-MTX

**Description:** 375mg/m2 intravenous infusion d1, every 3 weeks for 1 cycle, 6 cycles will be prescribed for induction therapy. 375mg/m2 intravenous infusion d1, every 8 weeks for 1 cycle, 4 cycles will be prescribed for maintenance therapy.

**Name:** Rituximab

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- R2-MTX

**Description:** 25mg orally d1-10 every 3 weeks for 1 cycle, 6 cycles will be prescribed for induction therapy. 25mg orally d1-14,d29-42 every 8 weeks for 1 cycle, 4 cycles will be prescribed for maintenance therapy.

**Name:** Lenalidomide

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- R2-MTX

**Description:** 3.5g/m2 intravenous infusion for 4 hours in d1, every 21 days for 1 cycle, 6 cycles will be prescribed.

**Name:** Methotrexate

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** The objective response rate is defined as the proportion of patients with a response of complete response(CR) or partial response(PR).

**Measure:** Objective response rate(ORR)

**Time Frame:** At the end of Cycle 6 chemotherapy (each cycle is 21 days), assessed up to 18 weeks.

#### Secondary Outcomes

**Description:** From date of patients sign informed consent until the date of progression or death or the date of last follow-up time, whichever came first, assessed up to 3 years

**Measure:** Progression free survival

**Time Frame:** 3 years

**Description:** From date of patients sign informed consent until the date of death or the date of last follow-up time, whichever came first, assessed up to 3 years

**Measure:** Overall survival

**Time Frame:** 3 years

**Description:** Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

**Measure:** Treatment-related adverse events

**Time Frame:** 1 year

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Histologically confirmed Primary Central Nervous System (CNS) lymphoma
2. Age range 18-75 years old.
3. Eastern Cooperative Oncology Group performance status 0 to 3.
4. Previously untreated. Patients treated with steroid alone are eligible.
5. Patient's who are not planned to undergo consolidation with autologous hematopoietic stem cell transplantation（HSCT）.
6. Measurable disease was defined as at least ≥1.0cm in short-diameter by MRI.
7. Life expectancy of ≥ 3 months (in the opinion of the investigator).
8. Participants must be able to understand and be willing to sign a written informed consent document.
9. Women of reproductive potential must agree to use highly effective methods of birth control during the period of therapy and for 6 months after the last dose of the study drug. Men who are sexually active must agree to use highly effective contraception during the period of therapy and for 6 months after the last dose.
10. Women of childbearing potential must have a negative plasma pregnancy test upon study entry.
11. Adequate renal function: Estimated glomerular filtration rate (GFR) or estimated creatinine clearance (CrCl) ≥ 50 mL/min;Serum creatinine ≤ 2 times the upper limit of normal.
12. Adequate liver functions: Transaminase (AST/ALT) \< 3 X upper normal value \& Bilirubin \< 2 X upper normal value.
13. Adequate hematological function: hemoglobin ≥ 9 g/dL absolute neutrophil count (ANC) ≥ 1,500/μL and platelet count ≥ 75,000/μL.

Exclusion Criteria:

1. Patient with systemic, non-CNS lymphoma metastatic to the CNS.
2. Patient is concurrently using other approved or investigational antineoplastic agents.
3. Presence of active hepatitis B virus(HBV) infection (HBsAg positive and HBV-DNA≥ 104), hepatitis C virus(HCV) infection, acquired and congenital immunodeficiency diseases include but not limited to HIV.
4. Patient is allergic to components of the study drug.
5. Patient has an active concurrent malignancy requiring active therapy.
6. Patient has significant abnormalities on screening electrocardiogram (EKG) and active and significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, uncontrolled congestive heart failure, uncontrolled hypertension, valvular disease, pericarditis, or myocardial infarction within 6 months of screening.
7. Patient is known to have an uncontrolled active systemic infection.
8. Patient has a life-threatening illness, medical condition, or organ system dysfunction that, in the opinion of the investigator, could compromise the subject's safety or put the study outcomes at undue risk.
9. Women who are pregnant or nursing (lactating), where pregnancy is defined as a state of a female after conception until the termination of gestation, confirmed by a positive plasma human chorionic gonadotropin(hCG) laboratory test of \> 5 mIU/mL.
10. The patient is unwell or unable to participate in all required study evaluations and procedures.
11. Drug abuse, medical, psychological or social conditions which may interfering with subjects' participation in the study or evaluation of the results.
12. Patients considered unsuitable to participate in the study by the researchers.

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Hangzhou

**Country:** China

**Facility:** 2nd Affiliated Hospital, School of Medicine, Zhejiang University

**State:** Zhejiang

**Zip:** 310009

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000008232

- Term: Lymphoproliferative Disorders

- ID: D000008206

- Term: Lymphatic Diseases

- ID: D000007160

- Term: Immunoproliferative Disorders

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M11220

- Name: Lymphoma

- Relevance: HIGH

- As Found: Lymphoma

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M11225

- Name: Lymphoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M11203

- Name: Lymphatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10206

- Name: Immunoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T3543

- Name: Lymphosarcoma

- Relevance: HIGH

- As Found: Lymphoma

- ID: T4686

- Name: Primary Central Nervous System Lymphoma

- Relevance: HIGH

- As Found: Primary Central Nervous System Lymphoma

### Condition Browse Module - Meshes

- ID: D000008223

- Term: Lymphoma

### Intervention Browse Module - Ancestors

- ID: D000074322

- Term: Antineoplastic Agents, Immunological

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000007155

- Term: Immunologic Factors

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000018501

- Term: Antirheumatic Agents

- ID: D000000020

- Term: Abortifacient Agents, Nonsteroidal

- ID: D000000019

- Term: Abortifacient Agents

- ID: D000012102

- Term: Reproductive Control Agents

- ID: D000000964

- Term: Antimetabolites, Antineoplastic

- ID: D000000963

- Term: Antimetabolites

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000003879

- Term: Dermatologic Agents

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000005493

- Term: Folic Acid Antagonists

- ID: D000007166

- Term: Immunosuppressive Agents

- ID: D000019384

- Term: Nucleic Acid Synthesis Inhibitors

- ID: D000020533

- Term: Angiogenesis Inhibitors

- ID: D000043924

- Term: Angiogenesis Modulating Agents

- ID: D000006133

- Term: Growth Substances

- ID: D000006131

- Term: Growth Inhibitors

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: Derm

- Name: Dermatologic Agents

- Abbrev: Repr

- Name: Reproductive Control Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Micro

- Name: Micronutrients

- Abbrev: Hemat

- Name: Hematinics

- Abbrev: Vi

- Name: Vitamins

### Intervention Browse Module - Browse Leaves

- ID: M11703

- Name: Methotrexate

- Relevance: HIGH

- As Found: Breast Cancer

- ID: M373

- Name: Rituximab

- Relevance: HIGH

- As Found: Healthy

- ID: M1725

- Name: Lenalidomide

- Relevance: HIGH

- As Found: Respiratory

- ID: M1346

- Name: Antineoplastic Agents, Immunological

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

- ID: M20604

- Name: Antirheumatic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4281

- Name: Antimetabolites

- Relevance: LOW

- As Found: Unknown

- ID: M7074

- Name: Dermatologic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M8618

- Name: Folic Acid

- Relevance: LOW

- As Found: Unknown

- ID: M17546

- Name: Vitamin B Complex

- Relevance: LOW

- As Found: Unknown

- ID: M8619

- Name: Folic Acid Antagonists

- Relevance: LOW

- As Found: Unknown

- ID: M10212

- Name: Immunosuppressive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M22318

- Name: Angiogenesis Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M9231

- Name: Growth Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: T447

- Name: Folinic Acid

- Relevance: LOW

- As Found: Unknown

- ID: T446

- Name: Folic Acid

- Relevance: LOW

- As Found: Unknown

- ID: T448

- Name: Folate

- Relevance: LOW

- As Found: Unknown

- ID: T475

- Name: Vitamin B9

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000069283

- Term: Rituximab

- ID: D000008727

- Term: Methotrexate

- ID: D000077269

- Term: Lenalidomide

### Misc Info Module

- Version Holder: 2024-05-24
