Study in Patients With Primary Breast Diffuse Large B-cell Lymphoma

NCT ID: NCT01448096

Last Updated: 2019-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2019-07-10

Brief Summary

The purpose of this study is to clarify the impact of rituximab on clinical outcomes in patients with primary breast diffuse large B-cell lymphoma and also to investigate the role of prophylactic intrathecal chemotherapy using methotrexate for reducing central nervous system (CNS) recurrence.

Detailed Description

Primary breast diffuse large B-cell lymphoma (DLBCL) is a rare presentation of non-Hodgkin's lymphoma. A significant risk of contralateral breast involvement and a tendency for central nervous system (CNS) progression have been identified in previous studies. Optimal treatment strategies for primary breast DLBCL have remained undefined, although the combination of anthracycline-based chemotherapy and radiotherapy may be considered to be the best treatment option in these studies. However, despite the administration of aggressive treatment, prognosis is still poor, even in localized disease, with 5-year progression-free survival rates of approximately 50% to 65% in most series. Therefore, other therapeutic options must be explored.

During the last decade, several studies have shown that rituximab plus CHOP or CHOP-like chemotherapy significantly improves clinical outcomes of patients with DLBCL. However, the relevance of rituximab in the management of this rare extranodal lymphoma has never been studied. Moreover, several studies have also suggested the possibility that prophylactic intrathecal chemotherapy might be effective in reducing CNS recurrence.

Thus, this trial is designed to prospectively evaluate the treatment strategy, which addressed the safety and efficacy of a combined therapy that included R-CHOP21 and prophylactic intrathecal chemotherapy using methotrexate.

Conditions

Large B Cell Diffuse Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

primary breast DLBCL

isolated breast involvement with or without nodal disease

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

R-CHOP21 consist of rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1.4 mg/m2, a maximum of 2mg), administered intravenously on day 1 and 100 mg oral prednisone on days 1 through 5.

Prophylactic intrathecal chemotherapy

Intervention Type: PROCEDURE

Prophylactic intrathecal chemotherapy using methotrexate (12mg total dose) will be performed

Interventions

Rituximab

R-CHOP21 consist of rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1.4 mg/m2, a maximum of 2mg), administered intravenously on day 1 and 100 mg oral prednisone on days 1 through 5.

Intervention Type: DRUG

Prophylactic intrathecal chemotherapy

Prophylactic intrathecal chemotherapy using methotrexate (12mg total dose) will be performed

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed CD20 positive primary breast DLBCL
• age ≤ 70
• No prior chemotherapy or radiotherapy for DLBCL
• Performance status (ECOG) ≤ 2
• Cardiac ejection fraction ≥ 50 % as measured by MUGA or 2D ECHO without clinically significant abnormalities
• Adequate renal function: serum creatinine level < 2 mg/dL (177 μmol/L)
• Adequate liver functions: Transaminase (AST/ALT) < 3 X upper normal value, Bilirubin < 2 X upper normal value
• Adequate BM functions: hemoglobin ≥ 9 g/dL absolute neutrophil count (ANC) ≥ 1,500/μL and platelet count ≥ 75,000/μL
• A negative serum or urine pregnancy test prior to treatment must be available both for pre menopausal women and for women who are < 1 years after the onset of menopause
• Life expectancy more than 6 months
• Informed consent

Exclusion Criteria

• other subtype primary breast non-Hodgkin's lymphoma than DLBCL
• secondary breast DLBCL
• Patients with a known history of HIV seropositivity or HCV (+). Patients who have HBV (+) are eligible. However, primary prophylaxis using antiviral agents (i.e. lamivudine) is recommended for HBV carrier to prevent HBV reactivation during whole treatment period.
• Any other malignancies within the past 5 years except curatively treated non-melanoma skin cancer or in situ carcinoma of cervix uteri
• Pregnant or lactating women, women of childbearing potential not employing adequate contraception
• Other serious illness or medical conditions

• Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry
• History of significant neurologic or psychiatric disorders including dementia or seizures
• Active uncontrolled infection (viral, bacterial or fungal infection)
• Other serious medical illnesses
• Known hypersensitivity to any of the study drugs or its ingredients (i.e., hypersensitivity to Polysorbate 20, CHO cell products, or recombinant human antibodies)
• Concomitant administration of any other experimental drug under investigation, or concomitant chemotherapy, hormonal therapy, or immunotherapy

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Consortium for Improving Survival of Lymphoma

OTHER

Sponsor Role: collaborator

Chonbuk National University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Ho-Young Yhim

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jae-Yong Kwak, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Chonbuk National University Hospital

Locations

Chonbuk National University Hospital

Jeonju, , South Korea

Countries

South Korea

References

Yhim HY, Kim JS, Kang HJ, Kim SJ, Kim WS, Choi CW, Eom HS, Kim JA, Lee JH, Won JH, Shim H, Huh J, Lee DH, Suh C, Kwak JY. Matched-pair analysis comparing the outcomes of primary breast and nodal diffuse large B-cell lymphoma in patients treated with rituximab plus chemotherapy. Int J Cancer. 2012 Jul 1;131(1):235-43. doi: 10.1002/ijc.26352. Epub 2011 Aug 30.

Reference Type: BACKGROUND

PMID: 21823120 (View on PubMed)

Yhim HY, Kang HJ, Choi YH, Kim SJ, Kim WS, Chae YS, Kim JS, Choi CW, Oh SY, Eom HS, Kim JA, Lee JH, Won JH, Shim H, Lee JJ, Sung HJ, Kim HJ, Lee DH, Suh C, Kwak JY. Clinical outcomes and prognostic factors in patients with breast diffuse large B cell lymphoma; Consortium for Improving Survival of Lymphoma (CISL) study. BMC Cancer. 2010 Jun 22;10:321. doi: 10.1186/1471-2407-10-321.

Reference Type: BACKGROUND

PMID: 20569446 (View on PubMed)

Other Identifiers

Chonbuk058

Identifier Type: -

Identifier Source: org_study_id