Combination Chemotherapy and Rituximab in Treating Patients With HIV-Associated Stage I, Stage II, Stage III, or Stage IV Non-Hodgkin's Lymphoma
- Full Text View
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Purpose
This randomized phase II trial is studying how well giving combination chemotherapy together with rituximab works in treating patients with HIV-associated stage I, stage II, stage III, or stage IV non-Hodgkin's lymphoma. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining chemotherapy with monoclonal antibody therapy may kill more cancer cells
| Condition | Intervention | Phase |
|---|---|---|
|
AIDS-related Diffuse Large Cell Lymphoma AIDS-related Immunoblastic Large Cell Lymphoma AIDS-related Peripheral/Systemic Lymphoma AIDS-related Small Noncleaved Cell Lymphoma |
Biological: rituximab Drug: etoposide Drug: doxorubicin hydrochloride Drug: vincristine sulfate Drug: prednisone Drug: cyclophosphamide Other: laboratory biomarker analysis |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Randomized Phase II Trial of EPOCH Given Either Concurrently or Sequentially With Rituximab in Patients With Intermediate- or High-Grade HIV-Associated B-cell Non-Hodgkin's Lymphoma |
- Complete Response Proportion as Measured by Tumor Response After Completion of Study Treatment [ Time Frame: 60 days ] [ Designated as safety issue: No ]Complete response defined by the International Response Criteria for Non-Hodgkin's Lymphoma
| Enrollment: | 70 |
| Study Start Date: | March 2003 |
| Primary Completion Date: | May 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I
Patients receive rituximab intravenously (IV) over 2-4 hours prior to each course of chemotherapy. Treatment repeats every 3 weeks for 4-6 courses. Patients who achieve a complete response after 4 courses of chemotherapy and rituximab receive additional rituximab alone weekly for 2 weeks.
|
Biological: rituximab
Given IV
Other Names:
Drug: etoposide
Given IV
Other Names:
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: vincristine sulfate
Given IV
Other Names:
Drug: prednisone
Given orally
Other Names:
Drug: cyclophosphamide
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
|
Experimental: Arm II
Patients do not receive rituximab concurrently with chemotherapy. Beginning 4 weeks after completion of chemotherapy, patients receive rituximab IV over 2-4 hours weekly for 6 weeks.
|
Biological: rituximab
Given IV
Other Names:
Drug: etoposide
Given IV
Other Names:
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: vincristine sulfate
Given IV
Other Names:
Drug: prednisone
Given orally
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine the complete response rate after treatment with EPOCH given either concurrently or sequentially with rituximab.
SECONDARY OBJECTIVES:
I. To evaluate the toxicity of EPOCH given either concurrently or sequentially with rituximab.
II. To evaluate the effect of EPOCH given either concurrently or sequentially with rituximab on immune function (CD4, CD8 lymphocyte count) after two cycles of EPOCH, and 1 month, 3 months, 6 months, and 12 months after the completion of EPOCH.
III. To evaluate the effect of EPOCH given either concurrently or sequentially with rituximab on HIV and EBV viral load after two cycles of EPOCH, and 1 month, 3 months, 6 months, and 12 months after the completion of EPOCH.
IV. To evaluate the relationship between EBV viral load and EBV CD8 cytotoxic T cells in the peripheral blood and the presence of EBV in lymphoma tumor cells.
V. To determine whether rituximab or the concurrent use of antiretroviral therapy significantly alters the steady state concentration of etoposide, doxorubicin, or vincristine during the first cycle of therapy.
VI. To determine whether steady state concentration of etoposide or doxorubicin correlate with nadir neutrophil and platelet count during the first cycle of therapy.
VII. To determine time to progression and overall survival in patients treated with EPOCH given either concurrently or sequentially with rituximab.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to CD4 count (less than 100/mm^3 vs at least 100/mm^3), age-adjusted International Prognostic Index adverse risk factors (0 or 1 vs 2 or 3), and concurrent antiretroviral therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive rituximab intravenously (IV) over 2-4 hours prior to each course of chemotherapy. Treatment repeats every 3 weeks for 4-6 courses. Patients who achieve a complete response after 4 courses of chemotherapy and rituximab receive additional rituximab alone weekly for 2 weeks.
ARM II: Patients do not receive rituximab concurrently with chemotherapy. Beginning 4 weeks after completion of chemotherapy, patients receive rituximab IV over 2-4 hours weekly for 6 weeks.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Previously untreated histologically or cytologically documented B-cell non-Hodgkin's lymphoma; the following histologies are eligible: diffuse large B-cell lymphoma, high-grade large cell immunoblastic lymphoma, anaplastic large cell lymphoma, Burkitt's lymphoma, high-grade B-cell lymphoma, Burkitt-like (small non-cleaved lymphoma)
- Tumors must be CD20 positive
- Documented HIV infection: documentation may be serologic (ELISA, western blot), culture, or quantitative PCR or bDNA assays
- Evaluable or measurable disease
- Stage I and IE or Stage II-IV disease patients
- ANC >= 1000 cells/mm^3
- Platelet count >= 75,000/mm^3 unless cytopenias are secondary to lymphoma
- All patients must be off colony stimulating factor therapy at least 24 hours prior to chemotherapy
- Transaminase =< 5 times the upper limit of normal unless secondary to hepatic infiltration with lymphoma or isolated hyperbilirubinemia associated with the use of indinavir or other antiretrovirals
- Total Bilirubin < 2.0 unless secondary to hepatic infiltration with lymphoma or isolated hyperbilirubinemia associated with the use of indinavir or other antiretrovirals; for bilirubin > 3.0 due to hepatic involvement the initial dose of doxorubicin will be decreased by 50% and the initial dose of vincristine will be omitted
- Creatinine < 2.0 unless due to lymphoma
- KPS >= 50 (ECOG PS 0, 1, or 2)
- Able to give consent
- Female patients must have a negative pregnancy test within 72 hours of entering into the study; males and females must agree to use adequate birth control if conception is possible during the study; women must avoid pregnancy and men avoid fathering children while in the study
- Patients already receiving erythropoeitin or G-CSF are eligible
- Patients must have a left ventricular ejection fraction that is at or above the lower institutional limits of normal, as assessed by nuclear scan or echocardiogram obtained within 12 weeks of registration
- Lymphomatous meningitis (patients with a positive CSF cytology are eligible)
Exclusion Criteria:
- Previous chemotherapy or radiotherapy for this lymphoma
- Primary Central Nervous System Lymphoma (parenchymal brain or spinal cord tumor)
- Acute active HIV-associated opportunistic infection requiring antibiotic treatment; patients with mycobacterium avium are not excluded; chronic therapy with potentially myelosuppressive agents is allowed provided that entry hematologic criteria are met
- Concurrent malignancy (excluding in situ cervical cancer, or non-metastatic non-melanomatous skin cancer, or Kaposi's sarcoma not requiring systemic chemotherapy)
- Previous therapy with rituximab within 12 months; patients treated with rituximab more than 12 months earlier are eligible only if it was given for indications other than the treatment of intermediate- or high-grade lymphoma (eg, low-grade lymphoma or ITP)
Contacts and Locations| United States, Maryland | |
| AIDS - Associated Malignancies Clinical Trials Consortium | |
| Rockville, Maryland, United States, 20850 | |
| Principal Investigator: | Joseph Sparano | AIDS Associated Malignancies Clinical Trials Consortium |
More Information
No publications provided by National Cancer Institute (NCI)
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00049036 History of Changes |
| Other Study ID Numbers: | NCI-2012-02926, AMC-034, U01CA070019, CDR0000257660 |
| Study First Received: | November 12, 2002 |
| Results First Received: | May 23, 2011 |
| Last Updated: | December 17, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Acquired Immunodeficiency Syndrome HIV Infections Lymphoma Lymphoma, Non-Hodgkin Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Immunoblastic Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Slow Virus Diseases Immunologic Deficiency Syndromes |
Immune System Diseases Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Antibodies, Monoclonal Cyclophosphamide Rituximab Doxorubicin Etoposide Prednisone Vincristine Immunologic Factors Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on February 21, 2013
