Combination Chemotherapy Followed by Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Relapsed or Refractory AIDS-Related Non-Hodgkin's Lymphoma

Sponsor

AIDS Malignancy Consortium (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00310128

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as etoposide, methylprednisolone, cytarabine, and cisplatin, 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 and yttrium Y 90 ibritumomab tiuxetan, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them without harming normal cells. Giving more than one drug (combination chemotherapy) together with rituximab and yttrium Y 90 ibritumomab tiuxetan may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with rituximab and yttrium Y 90 ibritumomab tiuxetan works in treating patients with relapsed or refractory AIDS-related non-Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
AIDS-related Lymphoma Adult Non-Hodgkin's Lymphoma Anaplastic Large Cell Lymphoma	Drug: cisplatin Drug: cytarabine Drug: etoposide Drug: methylprednisolone Drug: rituximab Drug: yttrium Y 90 ibritumomab tiuxetan Procedure: antibody therapy Procedure: biological therapy Procedure: chemotherapy Procedure: monoclonal antibody therapy Procedure: radiation therapy Procedure: radioimmunotherapy Procedure: radioisotope therapy	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2006

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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