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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


Phase 2
18 Years
N/A
Not Enrolling
Both
AIDS-related Diffuse Large Cell Lymphoma, AIDS-related Immunoblastic Large Cell Lymphoma, AIDS-related Peripheral/Systemic Lymphoma, AIDS-related Small Noncleaved Cell Lymphoma

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Trial Information

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


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.


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)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete Response Proportion as Measured by Tumor Response After Completion of Study Treatment

Outcome Description:

Complete response defined by the International Response Criteria for Non-Hodgkin's Lymphoma

Outcome Time Frame:

60 days

Safety Issue:

No

Principal Investigator

Joseph Sparano

Investigator Role:

Principal Investigator

Investigator Affiliation:

AIDS Associated Malignancies Clinical Trials Consortium

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02926

NCT ID:

NCT00049036

Start Date:

March 2003

Completion Date:

Related Keywords:

  • AIDS-related Diffuse Large Cell Lymphoma
  • AIDS-related Immunoblastic Large Cell Lymphoma
  • AIDS-related Peripheral/Systemic Lymphoma
  • AIDS-related Small Noncleaved Cell Lymphoma
  • Acquired Immunodeficiency Syndrome
  • HIV Infections
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic

Name

Location

AIDS - Associated Malignancies Clinical Trials ConsortiumRockville, Maryland  20850