Combination Chemotherapy and Rituximab in Treating Patients With Newly Diagnosed AIDS-Related B-Cell Non-Hodgkin's Lymphoma

Lymphoma Clinical Trial

Official title:

A Phase II Trial of Doxil, Rituximab, Cyclophosphamide, Vincristine, and Prednisone (DR-COP) in Patients With Newly Diagnosed AIDS-Associated B-Cell Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00389818
• Other study ID #: AMC-047
• Secondary ID: U01CA070019CDR00
• Status: Completed
• Phase: Phase 2
• Start date: January 2007
• Est. completion date: September 2011

Study information

• Verified date: May 2018
• Source: AIDS Malignancy Consortium
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: 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. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Giving combination chemotherapy together with rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with rituximab works in treating patients with newly diagnosed AIDS-related B-cell non-Hodgkin's lymphoma.

Description:

OBJECTIVES:

Primary

• Determine the complete response rate (complete response and complete response unconfirmed) in patients with newly diagnosed, AIDS-related B-cell non-Hodgkin's lymphoma treated with doxorubicin hydrochloride liposome, rituximab, cyclophosphamide, vincristine, and prednisone (DR-COP).

• Determine the duration of response (relapse-free survival) in patients treated with this regimen.

• Determine the median survival time of patients treated with this regimen.

• Determine rate of bacterial, fungal, and opportunistic infections in patients treated with this regimen.

Secondary

• Determine, preliminarily, the relationship between MDR-1 expression in tumor tissue and response to therapy in patients treated with this regimen.

• Determine, preliminarily, any relationship between response and survival and BCL-2 expression in tumor tissue in patients treated with this regimen.

• Determine any relationship between development of bacterial, fungal, and/or opportunistic infections and baseline CD4 lymphocyte count, HIV-1 RNA level, and quantitative immunoglobulin levels, or changes in quantitative immunoglobulin levels over time in patients treated with this regimen.

• Compare the results of positron emission tomography (PET) scanning with traditional CT scans in predicting response to therapy in these patients.

• Examine the relationship between chemotherapeutic drug levels and receipt of specific antiretroviral and/or anti-infective medications in these patients.

• Examine the mortality and the causes of death in patients treated with this regimen.

• Determine event-free survival at 1 year.

OUTLINE: This is a nonrandomized, multicenter study.

Patients receive doxorubicin hydrochloride liposome IV over 90 minutes, rituximab IV over 5-7 hours, cyclophosphamide IV over 1 hour, and vincristine IV over 1-2 minutes on day 1 and oral prednisone on days 1-5. Patients also receive filgrastim (G-CSF), sargramostim (GM-CSF), or pegfilgrastim beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21-28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo laboratory/biomarker studies at baseline and after every 2 courses of chemotherapy. Tissue is examined by immunohistochemistry for BCL-2, Ki67, and MDR-1, along with other markers.

After completion of study treatment, patients are followed periodically for 3 years.

PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed AIDS-related B-cell non-Hodgkin's lymphoma (NHL), including any of the following subtypes:

• Grade III follicular large cell lymphoma

• Diffuse large B-cell lymphoma

• Immunoblastic lymphoma

• Plasmablastic lymphoma

• Primary effusion lymphoma

• Previously untreated disease

• Any stage disease

• CD20 positive disease

• Must have documented HIV infection

• Documentation may be by serology (enzyme-linked immunosorbent assay, western blot), culture, or quantitative polymerase chain reaction or branched DNA assays

• Prior documentation of HIV seropositivity allowed

• Measurable or nonmeasurable disease

• Currently receiving effective highly active anti-retroviral therapy

• No primary CNS lymphoma, including parenchymal brain or spinal cord lymphoma

• No presence of leptomeningeal disease (positive cerebrospinal fluid for lymphoma) or presence of metastatic disease to brain, in terms of any mass lesion

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 OR Karnofsky PS 50-100%

• Life expectancy = 2 months

• Absolute granulocyte (neutrophil) count = 1,000/mm³ (unless secondary to lymphomatous involvement of bone marrow)

• Platelet count = 75,000/mm³ (unless secondary to lymphomatous involvement of bone marrow or due to HIV-related thrombocytopenia)

• Bilirubin = 2.0 mg/dL (unless elevated secondary to lymphomatous involvement of liver or biliary system or due to other HIV medications [e.g., indinavir, tenofavir, or atazanavir])

• SGOT = 5 times upper limit of normal

• Creatinine = 2.0 mg/dL OR creatinine clearance = 60 mL/min (unless secondary to renal involvement by lymphoma)

• LVEF normal by MUGA or echocardiogram

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 6 months after completion of study treatment

• No other malignancy, except nonmelanoma skin cancer, carcinoma in situ of the cervix, or Kaposi's sarcoma that does not require systemic therapy

• No serious, ongoing, nonmalignant disease or infection that would preclude study compliance, in the opinion of the investigator

• No history of cutaneous or mucocutaneous reactions, or diseases in the past, due to any cause, severe enough to cause hospitalization or an inability to eat or drink for = 2 days

• No acute, intercurrent infection that would preclude study treatment

• Patients with Mycobacterium avium are eligible

• No cardiovascular problems, including any of the following:

• Myocardial infarction within the past 6 months

• New York Heart Association class II-IV heart failure

• Uncontrolled angina

• Severe uncontrolled ventricular arrhythmias

• Clinically significant pericardial disease

• ECG evidence of acute ischemic or active conduction system abnormalities.

• No shortness of breath at rest

• Arterial PO_2 = 70 or pulse oximeter-derived O_2 saturation = 94% on room air (unless due to lymphomatous involvement of the lungs)

• Able to comply with study and provide adequate informed consent

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 4 weeks since prior major surgery (except diagnostic surgery)

• At least 12 months since prior rituximab unless it was only given for indications other than the treatment of aggressive lymphoma

• No prior cytotoxic chemotherapy or radiotherapy for this lymphoma

• Concurrent radiotherapy, with or without steroids, for emergency conditions secondary to lymphoma (i.e., CNS tumor or cord compression) allowed

• No zidovudine or zidovudine-containing regimen (including Combivir® or Trizivir®) during and for 2 months after completion of chemotherapy

• Concurrent erythropoietin or filgrastim (G-CSF) allowed

• Growth factor therapy must be discontinued = 24 hours prior to study entry

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• filgrastim
Supportive therapy: GF therapy with G-CSF, GM-CSF, or pegfilgrastim will be used in all patients, beginning on Day 3 of each cycle, until post nadir of blood counts from each chemotherapy cycle.
• pegfilgrastim
GF therapy with G-CSF, GM-CSF, or pegfilgrastim will be used in all patients, beginning on Day 3 of each cycle, until post nadir of blood counts from each chemotherapy cycle.
• rituximab
375 mg/m2 IV Day 1 of each cycle
• sargramostim
GF therapy with G-CSF, GM-CSF, or pegfilgrastim will be used in all patients, beginning on Day 3 of each cycle, until post nadir of blood counts from each chemotherapy cycle.

Drug:
• cyclophosphamide
750 mg/m2 IV Day 1 of each cycle
• pegylated liposomal doxorubicin hydrochloride
40 mg/m2 IV Day 1 of each cycle
• prednisone
100 mg PO Days 1-5 of each cycle
• vincristine sulfate
1.4 mg/m2 IV Day 1 (2.0 mg maximum) of each cycle

Other:
• immunohistochemistry staining method
tissue specimen collected at baseline
• laboratory biomarker analysis
tissue specimen collected at baseline

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston University Cancer Research Center	Boston	Massachusetts
United States	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	UCLA Clinical AIDS Research and Education (CARE) Center	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	University of Miami Sylvester Comprehensive Cancer Center - Miami	Miami	Florida
United States	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Joan Karnell Cancer Center at Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	Virginia Mason Medical Center	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
AIDS Malignancy Consortium	National Cancer Institute (NCI), The EMMES Corporation

Country where clinical trial is conducted

United States, 

References & Publications (1)

Levine AM, Noy A, Lee JY, Tam W, Ramos JC, Henry DH, Parekh S, Reid EG, Mitsuyasu R, Cooley T, Dezube BJ, Ratner L, Cesarman E, Tulpule A. Pegylated liposomal doxorubicin, rituximab, cyclophosphamide, vincristine, and prednisone in AIDS-related lymphoma: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response Rate (Complete Response and Complete Response Unconfirmed) Defined as Disappearance of All Evidence of Disease Based on Radiographic Findings on CT or MRI .		After cycles 2, 4, 6, 1 month after treatment discontinuation, every 2 months for 1 year after treatment discontinuation, every 6 months during the second and third years after treatment discontinuation
Primary	Duration of Response		After cycles 2, 4, 6, 1 month after treatment discontinuation, every 2 months for 1 year after treatment discontinuation, every 6 months during the second and third years after treatment discontinuation
Primary	Median Survival Time		After cycles 2, 4, 6, 1 month after treatment discontinuation, every 2 months for 1 year after treatment discontinuation, every 6 months during the second and third years after treatment discontinuation
Primary	Rate of Bacterial, Fungal, and Opportunistic Infections		After every cycle of treatment, 1 month after treatment discontinuation, every 2 months for 1 year after treatment discontinuation, every 6 months during the second and third years after treatment discontinuation
Secondary	Relationship Between MDR-1 Expression and Response to Treatment		Baseline
Secondary	Relationship Between Response and Survival and BCL-2 Expression in Tumor Tissue		Baseline, after cycles 4 and 6, 1 month after treatment discontinuation
Secondary	Relationship Between Development of Bacterial, Fungal, and/or Opportunistic Infections and Baseline CD4 Lymphocyte Count, HIV-1 RNA Level, and Quantitative Immunoglobin Level, or Changes in Quantitative Immunoglobin Levels Over Time		After every cycle of treatment, 1 month after treatment discontinuation, every 2 months for 1 year after treatment discontinuation, every 6 months during the second and third years after treatment discontinuation
Secondary	Mortality and Cause of Death		At any time through the third year after treatment discontinuation
Secondary	Event-free Survival at 1 Year		1 year post-treatment