Clinical trial NCT00101010: Rituximab and Combination Chemotherapy in Treating Older Patients With Diffuse Large B-Cell Lymphoma
Official title: A Phase II Study Of Rituximab-CHOP With Pegylated Liposomal Doxorubicin In Patients Older Than 60 Years Of Age With Untreated Aggressive B-Cell Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: 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
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Ortho Biotech, Inc.
First posted: 2005-01-10
Enrollment: 80
Sex: ALL
Minimum age (years): 61
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies, such as 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 work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating older patients with diffuse large B-cell lymphoma.

Detailed description: OBJECTIVES:

Primary

* Determine the clinical response rate in older patients with previously untreated aggressive diffuse large B-cell stage II-IV lymphoma treated with rituximab, cyclophosphamide, pegylated doxorubicin hydrochloride liposome (HCl), vincristine, and prednisone.
* Determine the cardiotoxicity and myelosuppression of this regimen in these patients.

Secondary

* Determine disease-free survival and overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive rituximab intravenous (IV), cyclophosphamide IV over 1-1½ hours, pegylated doxorubicin HCl liposome IV over 1 hour, and vincristine IV on day 1, and oral prednisone on days 1-5. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 6 and continuing until blood counts recover OR pegfilgrastim SC once on day 6 (24 hours after the completion of chemotherapy). Treatment repeats every 21 days for up to 8 courses in the absence of unacceptable toxicity, disease progression, active hepatitis B virus infection, or hepatitis. Patients with no response OR who achieve less than a partial response after 4 courses are removed from the study.

Patients are followed at 1 month, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter.

PROJECTED ACCRUAL: A maximum of 80 patients will be accrued for this study within 27 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed diffuse large B-cell lymphoma

  * Stage II, III, or IV disease
  * Previously untreated disease
* Measurable or evaluable disease
* No primary central nervous system (CNS) lymphoma or follicular B-cell lymphoma

PATIENT CHARACTERISTICS:

Age

* 61 and over

Performance status

* Zubrod 0-2

Life expectancy

* Not specified

Hematopoietic

* Absolute neutrophil count \> 1,000/mm\^3\*
* Platelet count \> 100,000/mm\^3\* NOTE: \* Unless due to lymphoma-related hypersplenism or bone marrow infiltration

Hepatic

* Bilirubin \< 2 mg/dL
* Hepatitis B surface antigen negative
* Hepatitis B core antibody negative
* Hepatitis C Virus antibody negative

Renal

* Creatinine \< 2 mg/dL

Cardiovascular

* left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram or ple gated acquisition (MUGA) scan
* No uncontrolled hypertension or cardiac symptoms
* Cardiologist consultation required for patients with stage A cardiac failure or any of the following known heart diseases:

  * Diastolic dysfunction
  * Prior coronary artery bypass graft
  * Prior percutaneous transluminal coronary angioplasty
  * Prior stent insertion
  * Prior radiotherapy to the chest
* No myocardial infarction within the past 6 months
* No New York Heart Association class II-IV heart failure
* No uncontrolled angina
* No severe uncontrolled ventricular arrhythmias
* No clinically significant pericardial disease
* No acute ischemic or active conduction system abnormality by electrocardiogram (EKG)

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* No psychiatric illness that would preclude study compliance or giving informed consent
* No other major life-threatening illness that would preclude study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* Not specified

Endocrine therapy

* Not specified

Radiotherapy

* See Cardiovascular

Surgery

* See Cardiovascular

Primary outcomes:
measure: Disease Response (Complete, Complete Unconfirmed, and Partial Responses) After 4 Courses
timeFrame: Evaluation after 12 weeks (4 cycles of 21 days)
measure: Number of Participants Experienced Grade 3 or Higher Cardiac Toxicity After Treatment: Cardiac Toxicity as Measured by Left Ventricular Ejection Fraction (LVEF) on Echocardiogram (ECHO) After 8 Courses
timeFrame: Up to 24 weeks (8 cycles of 21 days)
Secondary outcomes:
measure: Survival Rate
timeFrame: Up to 5 years
measure: Disease-free Survival
timeFrame: Up to 5 years or until disease progression
Other outcomes:
Locations:
city: Fort Smith
country: United States
facility: Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
state: Arkansas
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids
state: Michigan
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: Springfield
country: United States
facility: Cancer Research for the Ozarks
state: Missouri
city: East Syracuse
country: United States
facility: Hematology Oncology Associates of Central New York, PC - Northeast Center
state: New York
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Houston
country: United States
facility: University of Texas M.D. Anderson CCOP Research Base
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Maria A. Rodriguez, MD
role: STUDY_CHAIR
References: