Combination Chemotherapy and Rituximab in Treating Patients With Newly Diagnosed AIDS-Related B-Cell Non-Hodgkin's Lymphoma
This study has been completed.
Sponsor:
AIDS Malignancy Clinical Trials Consortium
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
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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:
Drug Information available for:
Cyclophosphamide
Prednisone
Vincristine sulfate
Doxorubicin
Doxorubicin hydrochloride
Filgrastim
Sargramostim
Lenograstim
Granulocyte colony-stimulating factor
Rituximab
Pegfilgrastim
U.S. FDA Resources
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
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 May 23, 2013