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Phase II Study of Induction Therapy Comprising Etoposide, Methylprednisolone, Cytarabine, and Cisplatin (ESHAP) Followed by Consolidation Therapy Comprising Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan in Patients With Relapsed or Refractory AIDS-Related Non-Hodgkin's Lymphoma


Phase 2
18 Years
N/A
Not Enrolling
Both
AIDS-related Lymphoma, Adult Non-Hodgkin's Lymphoma, Anaplastic Large Cell Lymphoma

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Trial Information

Phase II Study of Induction Therapy Comprising Etoposide, Methylprednisolone, Cytarabine, and Cisplatin (ESHAP) Followed by Consolidation Therapy Comprising Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan in Patients With Relapsed or Refractory AIDS-Related Non-Hodgkin's Lymphoma


OBJECTIVES:

Primary

- Determine the overall survival rate at one year in patients with relapsed or refractory
AIDS-related non-Hodgkin's lymphoma treated with consolidation therapy comprising
rituximab and yttrium Y 90 ibritumomab tiuxetan (radioimmunotherapy) given after
induction therapy comprising etoposide, methylprednisolone, cytarabine, and cisplatin
(ESHAP).

- Describe the toxicity profile of radioimmunotherapy as consolidation therapy, including
changes in immunologic and virologic parameters over time, in these patients.

- Determine the overall disease-free survival of patients receiving ESHAP as induction
therapy followed by radioimmunotherapy as consolidation therapy.

Secondary

- Determine the effect of ESHAP as induction therapy and radioimmunotherapy as
consolidation therapy on HIV-1 viral load, CD4 and CD8 cells, and quantitative
immunoglobulin levels in patients on concurrent highly active antiretroviral therapy
(HAART).

- Determine the objective response rates (complete and partial response) in patients
treated with this regimen.

- Determine the toxicity of ESHAP as induction therapy in these patients.

OUTLINE: This is a multicenter study.

- Induction therapy: Patients receive ESHAP chemotherapy comprising etoposide IV over 2
hours on days 1-4, methylprednisolone IV over 15-30 minutes on days 1-5, cisplatin IV
continuously over 96 hours on days 1-4, and cytarabine IV over 2 hours on day 5.
Treatment repeats every 21-28 days for up to 4 courses in the absence of disease
progression or unacceptable toxicity. Approximately 21-52 days after completion of
ESHAP chemotherapy, patients proceed to consolidation therapy.

- Consolidation therapy: Patients receive radioimmunotherapy comprising rituximab IV over
3-4 hours followed by indium In 111 ibritumomab tiuxetan (for radioimaging) IV over 10
minutes on day 1. Patients then undergo imaging on days 1 and 2. If biodistribution is
acceptable, patients receive rituximab IV over 3-4 hours followed by yttrium Y 90
ibritumomab tiuxetan IV over 10 minutes on day 8.

After completing study treatment, patients are followed every 2 months for 1 year and then
every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 33 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically or cytologically documented B-cell non-Hodgkin's lymphoma, including
any of the following histologic types:

- Follicular large B-cell lymphoma (follicular, grade 3)

- Follicular mixed cell lymphoma (follicular, grade 2)

- Diffuse mixed cell lymphoma

- Diffuse large B-cell lymphoma

- Immunoblastic lymphoma

- Burkitt or Burkitt-like lymphoma

- Anaplastic large cell lymphoma

- Primary effusion lymphoma

- All stages eligible

- Seropositive for HIV by any approved test or positive HIV-1 RNA in plasma at anytime
in the past

- Prior documentation of HIV seropositivity allowed

- Received 1 prior anthracycline-based regimen of curative intent

- No more than 1 prior regimen

- Measurable or evaluable disease

- Evaluable disease defined as not having bidimensional measurements (i.e., gastric or
marrow involvement) but can be followed for response by other diagnostic tests, such
as gallium scan, positron emission tomography (PET) imaging and/or bone marrow biopsy

- No primary CNS lymphoma

- Lymphomatous meningitis or brain metastasis eligible provided other measurable
systemic lymphomatous disease is also present

- Less than 25% bone marrow involvement with lymphoma

- Concurrent effective highly active anti-retroviral therapy (HAART) required at study
entry

- HIV viral load < 100,000 copies/mL if HAART was not used previously

PATIENT CHARACTERISTICS:

- Karnofsky performance status 50-100%

- Bilirubin ≤ 2.0 mg/dL (unless elevated due to lymphomatous involvement of the liver
or biliary tract OR due to other HIV medications [e.g., indinavir or atazanavir])

- Creatinine < 2.0 mg/dL (< 2.6 mg/dL if due to use of tenofovir or truvada) OR
creatinine clearance ≥ 60 mL/min

- Granulocyte count > 1,000/mm^3 (unless abnormal due to lymphomatous involvement of
the bone marrow)

- Platelet count > 75,000/mm^3 (unless abnormal due to lymphomatous involvement of the
bone marrow or HIV-related thrombocytopenia)

- No acute intercurrent infection that may interfere with study participation

- Mycobacterium avium allowed

- No second active tumor except nonmelanomatous skin cancer, carcinoma in situ of the
cervix, or Kaposi's sarcoma not requiring systemic chemotherapy

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 6 months after
completion of study treatment

- No serious, ongoing nonmalignant disease or infection that would compromise study
objectives

- No antimurine antibody (HAMA) reactivity

- No history of any cutaneous or mucocutaneous reaction from prior rituximab
administration

- No history of cutaneous or mucocutaneous reactions or diseases severe enough to cause
hospitalization or an inability to eat for ≥ 2 days

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Fully recovered from all toxicities associated with prior surgery, radiotherapy,
chemotherapy, or immunotherapy

- Prior chronic therapy with potentially myelosuppressive agents allowed provided
hematologic criteria are met at study entry

- No radiotherapy within the past 4 weeks, unless for emergency conditions secondary to
lymphoma (i.e., cord compression)

- No anticancer therapy within the past 3 weeks (6 weeks for nitrosourea or mitomycin
C)

- No rituximab within 6 weeks before study radioimmunotherapy

- No investigational agent(s) within the past 4 weeks, unless these are antiretroviral
agents available on a compassionate use basis

- No prior external beam radiotherapy to > 25% of active bone marrow (involved field or
regional)

- No major surgery, other than diagnostic surgery, within the past 4 weeks

- No prior myeloablative therapies with autologous bone marrow transplantation,
peripheral blood stem cell rescue, or failed stem cell collection

- No prior radioimmunotherapy

- No pegfilgrastim within 4 weeks before study radioimmunotherapy

- No other growth factors within 2 weeks before and after study radioimmunotherapy

- No other concurrent myelosuppressive antineoplastic agents after receipt of study
radioimmunotherapy until blood counts recover

- No zidovudine-containing regimens (including lamivudine and trizivir) during and for
≥ 2 months after completion of study radioimmunotherapy

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Alexandra M. Levine, MD

Investigator Role:

Study Chair

Investigator Affiliation:

USC/Norris Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000467797

NCT ID:

NCT00310128

Start Date:

February 2006

Completion Date:

Related Keywords:

  • AIDS-Related Lymphoma
  • Adult Non-Hodgkin's Lymphoma
  • Anaplastic Large Cell Lymphoma
  • AIDS-related diffuse large cell lymphoma
  • AIDS-related peripheral/systemic lymphoma
  • AIDS-related small noncleaved cell lymphoma
  • AIDS-related diffuse mixed cell lymphoma
  • AIDS-related immunoblastic large cell lymphoma
  • contiguous stage II grade 2 follicular lymphoma
  • contiguous stage II grade 3 follicular lymphoma
  • noncontiguous stage II grade 2 follicular lymphoma
  • noncontiguous stage II grade 3 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • stage I grade 2 follicular lymphoma
  • stage I grade 3 follicular lymphoma
  • stage III grade 2 follicular lymphoma
  • stage III grade 3 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • contiguous stage II adult Burkitt's lymphoma
  • noncontiguous stage II adult Burkitt's lymphoma
  • recurrent adult Burkitt's lymphoma
  • stage I adult Burkitt's lymphoma
  • stage III adult Burkitt's lymphoma
  • stage IV adult Burkitt's lymphoma
  • anaplastic large cell lymphoma
  • contiguous stage II adult diffuse large cell lymphoma
  • noncontiguous stage II adult diffuse large cell lymphoma
  • recurrent 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
  • contiguous stage II adult diffuse mixed cell lymphoma
  • noncontiguous stage II adult diffuse mixed cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • stage I adult diffuse mixed cell lymphoma
  • stage III adult diffuse mixed cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • contiguous stage II adult immunoblastic large cell lymphoma
  • noncontiguous stage II adult immunoblastic large cell lymphoma
  • recurrent 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
  • Acquired Immunodeficiency Syndrome
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Immunoblastic
  • Lymphoma, AIDS-Related
  • Lymphoma, Large-Cell, Anaplastic

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