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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


Phase 2
18 Years
N/A
Not Enrolling
Both
Lymphoma

Thank you

Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

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

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 .

Outcome 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

Safety Issue:

No

Principal Investigator

Alexandra M. Levine, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Beckman Research Institute

Authority:

United States: Institutional Review Board

Study ID:

CDR0000507634

NCT ID:

NCT00389818

Start Date:

January 2007

Completion Date:

September 2011

Related Keywords:

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

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065
Virginia Mason Medical CenterSeattle, Washington  98111
USC/Norris Comprehensive Cancer Center and HospitalLos Angeles, California  90033-0804
Rebecca and John Moores UCSD Cancer CenterLa Jolla, California  92093-0658
Ochsner Cancer Institute at Ochsner Clinic FoundationNew Orleans, Louisiana  70121
Albert Einstein Cancer Center at Albert Einstein College of MedicineBronx, New York  10461
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
Robert H. Lurie Comprehensive Cancer Center at Northwestern UniversityChicago, Illinois  60611
Joan Karnell Cancer Center at Pennsylvania HospitalPhiladelphia, Pennsylvania  19107
University of Miami Sylvester Comprehensive Cancer Center - MiamiMiami, Florida  33136
UCLA Clinical AIDS Research and Education (CARE) CenterLos Angeles, California  90024
Boston University Cancer Research CenterBoston, Massachusetts  02118