Combination Chemotherapy and Rituximab in Treating Patients With HIV-Associated Stage I, Stage II, Stage III, or Stage IV Non-Hodgkin's Lymphoma
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| ClinicalTrials.gov Identifier: NCT00049036 |
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Recruitment Status :
Completed
First Posted : January 27, 2003
Results First Posted : June 22, 2011
Last Update Posted : May 14, 2014
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| Condition or disease | Intervention/treatment | 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 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 106 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (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 |
| Study Start Date : | March 2003 |
| Actual Primary Completion Date : | May 2009 |
| Actual Study Completion Date : | May 2009 |
| Arm | Intervention/treatment |
|---|---|
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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.
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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 |
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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.
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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 |
- Complete Response Proportion as Measured by Tumor Response After Completion of Study Treatment [ Time Frame: 60 days ]Complete response defined by the International Response Criteria for Non-Hodgkin's Lymphoma
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| 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)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00049036
| United States, Maryland | |
| AIDS - Associated Malignancies Clinical Trials Consortium | |
| Rockville, Maryland, United States, 20850 | |
| Principal Investigator: | Joseph Sparano | AIDS Associated Malignancies Clinical Trials Consortium |
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00049036 |
| Other Study ID Numbers: |
NCI-2012-02926 NCI-2012-02926 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) ECOG-AMC34 CDR0000257660 AMC-034 ( Other Identifier: AIDS - Associated Malignancies Clinical Trials Consortium ) AMC-034 ( Other Identifier: CTEP ) U01CA070019 ( U.S. NIH Grant/Contract ) |
| First Posted: | January 27, 2003 Key Record Dates |
| Results First Posted: | June 22, 2011 |
| Last Update Posted: | May 14, 2014 |
| Last Verified: | December 2012 |
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Lymphoma Lymphoma, Non-Hodgkin Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Immunoblastic Plasmablastic Lymphoma Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, B-Cell Prednisone Cyclophosphamide Rituximab |
Doxorubicin Liposomal doxorubicin Etoposide Vincristine Etoposide phosphate Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antineoplastic Agents, Immunological |