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LymphomaPhase 2NCT00389818

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

A Phase 2 study testing filgrastim, pegfilgrastim and rituximab in people with Lymphoma, run by AIDS Malignancy Consortium at 14 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Lymphoma
What is being tested?
filgrastim, pegfilgrastim and rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
14 sitesUnited States
Study dates
Jan 2007to Sep 2011
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites

  • Boston University Cancer Research Center

    Boston, Massachusetts, 02118

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Robert H. Lurie Comprehensive Cancer Center at Northwestern University

    Chicago, Illinois, 60611-3013

  • Case Comprehensive Cancer Center

    Cleveland, Ohio, 44106-5065

  • Rebecca and John Moores UCSD Cancer Center

    La Jolla, California, 92093-0658

  • USC/Norris Comprehensive Cancer Center and Hospital

    Los Angeles, California, 90089-9181

  • UCLA Clinical AIDS Research and Education (CARE) Center

    Los Angeles, California, 90095-1793

  • University of Miami Sylvester Comprehensive Cancer Center - Miami

    Miami, Florida, 33136

  • Ochsner Cancer Institute at Ochsner Clinic Foundation

    New Orleans, Louisiana, 70121

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Joan Karnell Cancer Center at Pennsylvania Hospital

    Philadelphia, Pennsylvania, 19106

  • Virginia Mason Medical Center

    Seattle, Washington, 98101

  • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

    St Louis, Missouri, 63110

  • Albert Einstein Cancer Center at Albert Einstein College of Medicine

    The Bronx, New York, 10461

Other trials in United States

About this study

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

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.

Read the 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.

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
Medical subject headings
Lymphoma, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Large-Cell, Immunoblastic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • filgrastimBiological

    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.

  • pegfilgrastimBiological

    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.

  • rituximabBiological

    375 mg/m2 IV Day 1 of each cycle

  • sargramostimBiological

    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.

  • cyclophosphamideDrug

    750 mg/m2 IV Day 1 of each cycle

  • pegylated liposomal doxorubicin hydrochlorideDrug

    40 mg/m2 IV Day 1 of each cycle

  • prednisoneDrug

    100 mg PO Days 1-5 of each cycle

  • vincristine sulfateDrug

    1.4 mg/m2 IV Day 1 (2.0 mg maximum) of each cycle

  • immunohistochemistry staining methodOther

    tissue specimen collected at baseline

  • laboratory biomarker analysisOther

    tissue specimen collected at baseline

Study groups in NCT00389818
Study groupRoleWhat they receive
DR-COPExperimentalSingle arm interventional study: all subjects receive DR-COP regimen.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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 .

    Measured: 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

  2. Duration of Response

    Measured: 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

  3. Median Survival Time

    Measured: 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

  4. Rate of Bacterial, Fungal, and Opportunistic Infections

    Measured: 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 (5)

  1. Relationship Between MDR-1 Expression and Response to Treatment

    Measured: Baseline

  2. Relationship Between Response and Survival and BCL-2 Expression in Tumor Tissue

    Measured: Baseline, after cycles 4 and 6, 1 month after treatment discontinuation

  3. 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

    Measured: 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

  4. Mortality and Cause of Death

    Measured: At any time through the third year after treatment discontinuation

  5. Event-free Survival at 1 Year

    Measured: 1 year post-treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Oct 2006 (estimated)
  2. Study startJan 2007
  3. Primary completionSep 2011
  4. Study completionSep 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00389818
Sponsor's protocol ID
AMC-047
Other IDs
U01CA070019, CDR0000507634
Status last verified
May 2018
First submitted
18 Oct 2006
Last updated
6 Jun 2018
Data monitoring committee
No

Publications

  • 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.

    PubMed 23169503

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing filgrastim, pegfilgrastim and rituximab in people with Lymphoma, run by AIDS Malignancy Consortium at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jun 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 . (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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00389818, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2018.

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