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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Malignancy Clinical Trials Consortium
ClinicalTrials.gov Identifier:
NCT00389818
First received: October 18, 2006
Last updated: June 28, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Lymphoma
Biological: filgrastim
Biological: pegfilgrastim
Biological: rituximab
Biological: sargramostim
Drug: cyclophosphamide
Drug: pegylated liposomal doxorubicin hydrochloride
Drug: prednisone
Drug: vincristine sulfate
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by AIDS Malignancy Clinical Trials Consortium:

Primary Outcome Measures:
  • 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 . [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Duration of Response [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Median Survival Time [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Rate of Bacterial, Fungal, and Opportunistic Infections [ Time Frame: 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Relationship Between MDR-1 Expression and Response to Treatment [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Relationship Between Response and Survival and BCL-2 Expression in Tumor Tissue [ Time Frame: Baseline, after cycles 4 and 6, 1 month after treatment discontinuation ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Mortality and Cause of Death [ Time Frame: At any time through the third year after treatment discontinuation ] [ Designated as safety issue: No ]
  • Event-free Survival at 1 Year [ Time Frame: 1 year post-treatment ] [ Designated as safety issue: No ]

Enrollment: 43
Study Start Date: January 2007
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DR-COP
Single arm interventional study: all subjects receive DR-COP regimen.
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.
Biological: 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.
Biological: rituximab
375 mg/m2 IV Day 1 of each cycle
Biological: 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
Drug: pegylated liposomal doxorubicin hydrochloride
40 mg/m2 IV Day 1 of each cycle
Drug: prednisone
100 mg PO Days 1-5 of each cycle
Drug: 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
Other: laboratory biomarker analysis
tissue specimen collected at baseline

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00389818

Locations
United States, California
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, United States, 92093-0658
UCLA Clinical AIDS Research and Education (CARE) Center
Los Angeles, California, United States, 90095-1793
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
United States, Florida
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, United States, 33136
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
United States, Louisiana
Ochsner Cancer Institute at Ochsner Clinic Foundation
New Orleans, Louisiana, United States, 70121
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Boston University Cancer Research Center
Boston, Massachusetts, United States, 02118
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Saint Louis, Missouri, United States, 63110
United States, New York
Albert Einstein Cancer Center at Albert Einstein College of Medicine
Bronx, New York, United States, 10461
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Ohio
Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
United States, Pennsylvania
Joan Karnell Cancer Center at Pennsylvania Hospital
Philadelphia, Pennsylvania, United States, 19106
United States, Washington
Virginia Mason Medical Center
Seattle, Washington, United States, 98101
Sponsors and Collaborators
AIDS Malignancy Clinical Trials Consortium
Investigators
Study Chair: Alexandra M. Levine, MD Beckman Research Institute
  More Information

Additional Information:
No publications provided by AIDS Malignancy Clinical Trials Consortium

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AIDS Malignancy Clinical Trials Consortium
ClinicalTrials.gov Identifier: NCT00389818     History of Changes
Other Study ID Numbers: CDR0000507634, U01CA070019, AMC-047
Study First Received: October 18, 2006
Results First Received: May 29, 2012
Last Updated: June 28, 2012
Health Authority: United States: Institutional Review Board
United States: Federal Government

Keywords provided by AIDS Malignancy Clinical Trials Consortium:
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

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large-Cell, Immunoblastic
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Doxorubicin
Prednisone
Vincristine
Lenograstim
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
Antibiotics, Antineoplastic
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on July 20, 2014