Monoclonal Antibody Therapy and Combination Chemotherapy in Treating Patients With Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma - Full Text View

Sponsors and Collaborators:	North Central Cancer Treatment Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00301821

Purpose

RATIONALE: Monoclonal antibodies, such as epratuzumab and rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving monoclonal antibody therapy together with chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving monoclonal antibody therapy together with combination chemotherapy works in treating patients with stage II, stage III, or stage IV diffuse large B-cell lymphoma.

Condition	Intervention	Phase
Lymphoma	Biological: epratuzumab Biological: rituximab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate	Phase II

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Cyclophosphamide Prednisone Vincristine Doxorubicin Doxorubicin hydrochloride Myocet Rituximab Epratuzumab Yttrium Y 90 Epratuzumab Vincristine sulfate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase II Study of Epratuzumab, Rituximab (ER)-CHOP for Patients With Previously Untreated Diffuse Large B-Cell Lymphoma

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Response rate as assessed by complete response (CR) and partial response (PR) rates at end of treatment [ Designated as safety issue: No ]
Event-free survival after 12 months [ Designated as safety issue: No ]
Overall survival after 12 months [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity as assessed by incidence of neutropenia during each course of treatment [ Designated as safety issue: Yes ]

Estimated Enrollment:	86
Study Start Date:	January 2006

Detailed Description:

OBJECTIVES:

Primary

Assess the efficacy of epratuzumab and rituximab in combination with cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (CHOP), as measured by 12-month, event-free survival, in patients with previously untreated stage II, III, or IV diffuse large B-cell lymphoma.
Assess the use of positron emission tomography (PET) scan routinely early in treatment and after completion of treatment.
Assess the functional response rate (complete response, partial response, or stable disease by CT scan and PET negative) in patients treated with this regimen.
Assess the safety of this treatment regimen.

Secondary

Correlate laboratory prognostic factors for large cell lymphoma with clinical response to this regimen.

OUTLINE: This is a multicenter study.

Patients receive epratuzumab IV over 1 hour on day 1, rituximab IV over 4-8 hours on day 1 or days 1 and 2, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1 or 2, and oral prednisone on days 1-5 or 2-6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 86 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed diffuse large B-cell lymphoma
- B-cell phenotype (CD20+) as determined by immunohistochemistry (IHC) or flow cytometry
- Stage II, III, or IV disease
CD22+ tumor by IHC* NOTE: *CD22 status may be determined after study enrollment
Measurable disease, defined as at least 1 lesion ≥ 1.5 cm by CT scan or physical exam
No relapsed or refractory non-Hodgkin's lymphoma
No history of transformed lymphoma
No CNS lymphoma
- CNS symptoms or bone marrow or sinus involvement must have absence of CNS lymphoma confirmed by lumbar puncture

PATIENT CHARACTERISTICS:

ECOG performance status (PS) 0-3
- For patients with ECOG PS 3, the PS must be disease related
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Total bilirubin ≤ 2 mg/dL (if total bilirubin > 2 mg/dL, direct bilirubin should be within normal limits)
AST ≤ 3 times upper limit of normal (ULN) (5 times ULN if there is liver involvement)
Creatinine ≤ 2 times ULN
Life expectancy ≥ 12 weeks
Negative pregnancy test
Not pregnant or nursing
Fertile patients must use effective contraception during and for 12 months after completion of study treatment
No active serious infection requiring antibiotics
No New York Heart Association class III or IV heart disease
No other primary malignancy within the past 5 years, except for squamous cell or basal cell carcinoma of the skin, in situ carcinoma of the cervix, or previously treated prostate cancer with a stable prostate-specific antigen
No known HIV positivity
No known hepatitis B or C infection
Ejection fraction ≥ 45% by MUGA or echocardiogram (required if patients has a history of heart disease or is ≥ 50 years old)
Willing to provide blood and tissue samples for mandatory translational research component of study

PRIOR CONCURRENT THERAPY:

No prior therapy for diffuse large B-cell lymphoma, including the following:
- Chemotherapy
- Immunotherapy
- Biologic therapy
- Radiotherapy
Prior short course (≤ 14 days) of corticosteroids allowed
Prior splenectomy allowed
No prior pelvic irradiation
No other concurrent investigational agents
No concurrent chemotherapy, immunotherapy, or radiotherapy
No concurrent enrollment on another treatment study involving a pharmacologic agent (e.g., drugs, biologics, immunotherapy, or gene therapy)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00301821

Show 164 Study Locations

Sponsors and Collaborators

North Central Cancer Treatment Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Ivana Micallef, MD	Mayo Clinic
Investigator:	Daniel Nikcevich, MD, PhD	Duluth Clinic Cancer Center - Duluth
Investigator:	Thomas E. Witzig, MD	Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Micallef IN, Kahl BS, Maurer MJ, Dogan A, Ansell SM, Colgan JP, Geyer S, Inwards DJ, White WL, Habermann TM. A pilot study of epratuzumab and rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated, diffuse large B-cell lymphoma. Cancer. 2006 Dec 15;107(12):2826-32.

Study ID Numbers:	CDR0000459932, NCCTG-N0489
Study First Received:	March 9, 2006
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00301821 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma

Study placed in the following topic categories:

Anti-Inflammatory Agents
Prednisone
Immunologic Factors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Cyclophosphamide
Hormones
Lymphoma, B-Cell
Antibodies, Monoclonal
Anti-Bacterial Agents
Lymphoma, Large-cell
Lymphoma
Alkylating Agents
Immunoglobulins
Lymphoma, Large B-Cell, Diffuse

Immunoproliferative Disorders
Antineoplastic Agents, Hormonal
Rituximab
Vincristine
Antimitotic Agents
Immunosuppressive Agents
Glucocorticoids
Doxorubicin
Lymphatic Diseases
Antibodies
B-cell Lymphomas
Tubulin Modulators
Antineoplastic Agents, Alkylating
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Prednisone
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Cyclophosphamide
Antibiotics, Antineoplastic
Hormones
Lymphoma, B-Cell
Therapeutic Uses
Lymphoma
Alkylating Agents
Lymphoma, Large B-Cell, Diffuse

Immunoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Rituximab
Mitosis Modulators
Vincristine
Antimitotic Agents
Glucocorticoids
Immunosuppressive Agents
Doxorubicin
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Tubulin Modulators

ClinicalTrials.gov processed this record on May 07, 2009