Clinical trial NCT00389818: Combination Chemotherapy and Rituximab in Treating Patients With Newly Diagnosed AIDS-Related B-Cell Non-Hodgkin's Lymphoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: contiguous stage II grade 3 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
stage I grade 3 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 3 follicular lymphoma
AIDS-related diffuse large cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
stage I adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
AIDS-related immunoblastic large cell lymphoma
contiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
stage I adult immunoblastic large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
AIDS-related peripheral/systemic lymphoma
Lead sponsor: AIDS Malignancy Consortium
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: The Emmes Company, LLC
First posted: 2006-10-19
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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 .
timeFrame: 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
measure: Duration of Response
timeFrame: 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
measure: Median Survival Time
timeFrame: 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
measure: Rate of Bacterial, Fungal, and Opportunistic Infections
timeFrame: 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 outcomes:
measure: Relationship Between MDR-1 Expression and Response to Treatment
timeFrame: Baseline
measure: Relationship Between Response and Survival and BCL-2 Expression in Tumor Tissue
timeFrame: Baseline, after cycles 4 and 6, 1 month after treatment discontinuation
measure: 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
timeFrame: 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
measure: Mortality and Cause of Death
timeFrame: At any time through the third year after treatment discontinuation
measure: Event-free Survival at 1 Year
timeFrame: 1 year post-treatment
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Los Angeles
country: United States
facility: UCLA Clinical AIDS Research and Education (CARE) Center
state: California
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center - Miami
state: Florida
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Cancer Institute at Ochsner Clinic Foundation
state: Louisiana
city: Boston
country: United States
facility: Boston University Cancer Research Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Bronx
country: United States
facility: Albert Einstein Cancer Center at Albert Einstein College of Medicine
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: Joan Karnell Cancer Center at Pennsylvania Hospital
state: Pennsylvania
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
Study officials:
affiliation: City of Hope Comprehensive Cancer Center
name: Alexandra M. Levine, MD
role: STUDY_CHAIR
References:
citation: 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: AIDS Malignancy Consortium Study 047. J Clin Oncol. 2013 Jan 1;31(1):58-64. doi: 10.1200/JCO.2012.42.4648. Epub 2012 Nov 19.