Phase II study of lenalidomide-R-CHOP for patients with diffuse large B cell lymphoma who are at high risk of central nervous system relapse
- Conditions
- Neoplasms
- Registration Number
- KCT0005165
- Lead Sponsor
- Asan Medical Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot yet recruiting
- Sex
- All
- Target Recruitment
- 100
1. 19 years of age or older (ECOG PS 0-1 if subjects are 80 years of age or older, and can be registered at the discretion of the investigator if each organ score is = 2 using the Cumulative Illness Rating Scale (CIRS) for comorbid diseases)
2. Understand and voluntarily sign an informed consent document.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Histologically confirmed CD20+ DLBCL.
5. No prior treatment for DLBCL.
6. High-risk CNS relapse group who meet one or more of the following criteria.
a. CNS IPI score 4 or higher
b. One or more of the CNS relapse high-risk invasion as following : testicles, breast, adrenal glands, kidneys
c. Double expressor(MYC/BCL2 positive) and CNS IPI intermediate or higher (= 2)
7. Performance status = 2 on the Eastern Cooperative Oncology Group (ECOG) scale.
8. Must fulfill the following laboratory requirements:
a. Absolute neutrophil count (ANC) = 1,500 cells/mm3 (1.5 x 109/L) (secondary to bone marrow or spleen involvement by lymphoma = 1,000 cells/mm3 )
b. Platelet count = 75,000/mm3 (75 x 109/L) (secondary to bone marrow or spleen involvement by lymphoma = 50,000/ mm3)
c. Hemoglobin = 7.5 g/dL (4.7 mmol/L)
d. Serum aspartate transaminase (AST/SGOT) and alanine transaminase (ALT/SGPT) = 3.0 x upper limit of normal (ULN) (In the case of documented liver involvement by lymphoma, the requirement is = 5.0 x ULN)
e. Serum total bilirubin = 2.0 mg/dl (34 µmol/L) (In the case of Gilberts Syndrome, or documented liver or pancreatic involvement by lymphoma, the requirement is = 5.0 mg/dl)
f. Calculated creatinine clearance (Cockcroft-Gault formula) of = 30 mL/min
9. Even if HBsAg is positive, HBV DNA <500 IU / mL, and if the antiviral agent has been taken for 2 weeks or more as of the start date of treatment, it is possible to register if there is a willingness to follow the antiviral treatment guidelines during the clinical trial period. If HBsAg negative and HBcIgG Ab is positive, registration is possible if the subject receive prophylactic antiviral treatment.
10. Inactive hepatitis C carrier (normal aminotransferase, non-detection of HCV RNA in blood) is possible to register.
11. Females of childbearing potential (FCBP) must:
a. Have one negative pregnancy tests as verified prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the subject practices complete abstinence from heterosexual contact.
b. Either commit to complete abstinence from heterosexual contact (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting study therapy, during the study therapy (including dose interruptions), and for 12 months after discontinuation of study therapy.
12. Male subjects must:
a. Practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following investigational product discontinuation, even if he has undergone a successful vasectomy.
b. Agree to not donate semen during investigational product therapy and for 28 days after discontinuation of investigational product therapy.
13. All subjects must:
1. The following WHO subcategories of DLBCL:
a. Primary cutaneous, leg type
b. Primary mediastinal (thymic)
c. Lymphomatoid granulomatosis
d. ALK-positive lymphoma
e. Plasmablastic lymphoma
f. Large B-cell lymphoma arising in HHV8 associated multicentric Castleman disease
g. Primary effusion lymphoma
h. Intravascular large B-cell
i. B-cell unclassifiable cases with features intermediate between DLBCL and Burkitt
j. Unclassifiable cases with features intermediate between DLBCL and classical Hodgkin’s lymphoma
k. T cell / histiocyte rich
2. Post-transplant Lymphoproliferative Disorder (PTLPD) cases.
3. Histology other than DLBCL. Evidence of composite DLBCL and FL, or of transformed NHL.
4. DLBCL treatment with previous immunotherapy or chemotherapy, except for short-term corticosteroids (10 days or less)
5. In case of central nervous system invasion in imaging or cerebrospinal fluid cell examination.
6. Contraindication to any drug in the chemotherapy regimen, and specifically:
a. LVEF < 45% as assessed by MUGA, or LVEF
b. Peripheral neuropathy = Grade 2
c. Patients who have received doxorubicin in excess of 200 mg/m2
7. Known seropositive with human immunodeficiency virus(HIV).
8. HBV infection without proper treatment
9. Active HCV infection
10. Patients with other malignant tumors within the last 5 years except for fully curable skin basal cell carcinoma, non-metastatic cervical cancer, thyroid papillary cancer, and early gastric cancer.
11. Major surgery (excluding lymph node or bone marrow biopsy) within 28 days.
12. Use of any investigational agent within 28 days of Cycle 1 Day 1
13. Prior use of lenalidomide.
14. Known allergy or hypersensitive to thalidomide and lenalidomide.
15. Known sensitivity or allergy to murine products
16. Patient with genetic problems such as galactose intolerance (eg, angioedema, Stevens-Jones syndrome, addictive epidermal hyperplasia, etc.) or glucose-galactose uptake disorders.
17. Unwilling to take VTE prophylaxis.
18. Other severe diseases or medical conditions:
a. Heart disease not stable despite treatment
b. Patients with myocardial infarction or unstable angina within 3 months from the start of clinical trial enrollment
c. A history of significant neurological or psychiatric disorders, including dementia or epilepsy
d. Uncontrolled hypertension (systolic blood pressure> 180 mmHg at the time of screening test)
e. Uncontrolled clinically significant active hepatitis
f. Other serious medical conditions
19. Pregnant or lactating females.
20. Uncontrolled intercurrent illness.
21. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
22. Any condition, such as an active, severe infection, or the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
23. Any condition that confounds the ability to interpret data from the study.
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 2-year CNS relapse rate
- Secondary Outcome Measures
Name Time Method Time to CNS recurrence, TTR;Response rate, RR;Progression-free survival, PFS;Overall surviva, OS;Overall survival after CNS recurrence;Toxicity assessment according to NCI-CTCAE v5.0