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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Chonbuk National University Hospital
Sponsor:
Collaborator:
Consortium for Improving Survival on Lymphoma
Information provided by (Responsible Party):
Ho-Young Yhim, Chonbuk National University Hospital
ClinicalTrials.gov Identifier:
NCT01448096
First received: October 5, 2011
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Large B Cell Diffuse Lymphoma
Drug: Rituximab
Procedure: Prophylactic intrathecal chemotherapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multi-center Phase II Study of the Combination of R-CHOP (RItuximab Plus Cyclophosphamide, Adriamycin, Vincristine, and Prednisolone) and Prophylactic Intrathecal Chemotherapy With Methotrexate in Patients With CD20+ Primary Breast Diffuse Large B-cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Chonbuk National University Hospital:

Primary Outcome Measures:
  • progression-free survival [ Time Frame: From the date of treatment until the date of disease progression or death from any cause (minimum 2 years) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • overall survival [ Time Frame: From the date of treatment until the date of death from any cause (minimum 2 years) ] [ Designated as safety issue: No ]
  • Number of patients with CNS recurrence [ Time Frame: From the date of treatment until the date of CNS recurrrence (minimum 2 years) ] [ Designated as safety issue: No ]
  • Number of patients with adverse events [ Time Frame: From the first date of treatment until 30 days after the last treatment ] [ Designated as safety issue: Yes ]
    safety of a combined treatment of R-CHOP21 and prophylactic intrathecal chemotherapy according to the NCI-CTCAE ver.3.0


Estimated Enrollment: 33
Study Start Date: August 2011
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: 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.
    Procedure: Prophylactic intrathecal chemotherapy
    Prophylactic intrathecal chemotherapy using methotrexate (12mg total dose) will be performed
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.

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01448096

Contacts
Contact: Ho-Young Yhim, MD 82-63-250-1791 yhimhy@jbnu.ac.kr

Locations
Korea, Republic of
Chonbuk National University Hospital Recruiting
Jeonju, Korea, Republic of, 561-712
Contact: Ho-Young Yhim, MD    82-63-250-1791    yhimhy@jbnu.ac.kr   
Principal Investigator: Jae-Yong Kwak, MD, PhD         
Sponsors and Collaborators
Chonbuk National University Hospital
Consortium for Improving Survival on Lymphoma
Investigators
Principal Investigator: Jae-Yong Kwak, MD, PhD Chonbuk National University Hospital
  More Information

Publications:
Yhim HY, Kang HJ et al. 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

Responsible Party: Ho-Young Yhim, Principal investigator, Chonbuk National University Hospital
ClinicalTrials.gov Identifier: NCT01448096     History of Changes
Other Study ID Numbers: Chonbuk058
Study First Received: October 5, 2011
Last Updated: January 27, 2014
Health Authority: Korea: Food and Drug Administration

Keywords provided by Chonbuk National University Hospital:
primary breast diffuse large B cell lymphoma
rituximab
prophylactic intrathecal chemotherapy
CNS recurrence
Primary breast diffuse large B cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Rituximab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 18, 2014