Rituximab, Yttrium Y 90 Ibritumomab Tiuxetan in Patients W/Relapsed Stage II, III, or IV Follicular NHL
Condition: Lymphoma
MeSH terms: Lymphoma
Intervention: Methylprednisolone; Etoposide; Cytarabine; Cisplatin; Rituximab; In-Zevalin; Y-Zevalin
Intervention description: 250 mg/m2/day IV over 1 hour days 1,2,3,4 every 28 days for 2 cycles. If bone marrow <25% involved and expected biodistribution after 2 cycles yttrium-90-ibritumomab tiuxetan (Zevalin) to be administered.; 40 mg/day IV over 1 hour days 1,2,3,4 every 28 days for 2 cycles. If bone marrow <25% involved and expected biodistribution after 2 cycles yttrium-90-ibritumomab tiuxetan (Zevalin) to be administered.; 2000 mg/m2 IV over 2 hours days 4 every 28 days for 2 cycles. If bone marrow <25% involved and expected biodistribution after 2 cycles yttrium-90-ibritumomab tiuxetan (Zevalin) to be administered.; 25 mg/m2/day IV at 1mg/min days 1,2,3,4 every 28 days for 2 cycles. If bone marrow <25% involved and expected biodistribution after 2 cycles yttrium-90-ibritumomab tiuxetan (Zevalin) to be administered.; 250 mg/m2 slow IV over days 1, then 7,8 or 9 prior to In Zevalin. Rituximab + Zevalin regimen is given 4-6 weeks after completion of 2 cycles of ESHAP. Treatment can be completed within 7-9 days in an outpatient setting.; 5 mCi slow IV push over 10 minutes days 1. Given within 4 hours after Rituximab.; Platelet counts from 100,000/mm3 to 149,000/mm3 will receive 0.3 mCi/kg. Platelet counts from >/= 150,000/mm3 will receive 0.4 mCi/kg, not to exceed 32 mCi Y Zevalin. Slow IV push over 10 minutes, days 7,8 or 9 given within 4 hours after Rituximab.
Intervention MeSH terms: Cytarabine; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Rituximab; Etoposide; Antibodies, Monoclonal; Prednisolone hemisuccinate; Prednisolone phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: contiguous stage II grade 1 follicular lymphoma; contiguous stage II grade 2 follicular lymphoma; contiguous stage II grade 3 follicular lymphoma; noncontiguous stage II grade 1 follicular lymphoma; noncontiguous stage II grade 2 follicular lymphoma; noncontiguous stage II grade 3 follicular lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma

Summary:

      RATIONALE: Drugs used in chemotherapy 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, 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. Radiolabeled monoclonal antibodies, such as yttrium Y 90
      ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them
      without harming normal cells. Giving combination chemotherapy together with rituximab and
      yttrium Y 90 ibritumomab tiuxetan may kill more cancer cells.

      PURPOSE: This phase II trial is studying giving combination chemotherapy followed by
      rituximab and yttrium Y 90 ibritumomab tiuxetan to see how well it works in treating patients
      with relapsed stage II, stage III, or stage IV follicular non-Hodgkin lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of follicular non-Hodgkin lymphoma (NHL)

          -  Bulky stage II, stage III, or stage IV disease, Bulky disease is defined as any tumor
             measuring 10.0 cm or more or occupying ≥ one-third of the chest diameter

          -  In first, second, third, or fourth relapse after chemotherapy

          -  Unilateral or bilateral bone marrow aspirate and biopsy with cytogenetics within the
             past 42 days

          -  Tumor CD20 positive by either flow cytometry or immunoperoxidase staining of paraffin
             sections using anti-CD20 antibodies

          -  Bidimensionally measurable disease

          -  Patients with non-measurable disease in addition to measurable disease must have all
             non-measurable disease assessed within the past 42 days

          -  No presence of CNS lymphoma

          -  No chronic lymphocytic leukemia

          -  No HIV- or AIDS-related lymphoma

          -  No presence of pleural effusion

          -  Zubrod performance status 0-2

          -  ANC ≥ 1,500/μL (unless decreased counts are due to marrow involvement with NHL)

          -  Platelet count > 100,000/μL (unless decreased counts are due to marrow involvement
             with NHL)

          -  Serum creatinine ≤ 2.0 mg/dL

          -  Creatinine clearance ≤ 50 mL/min

          -  Serum bilirubin ≤ 2.0 mg/dL

          -  No renal insufficiency or renal failure

          -  No known HIV positivity

          -  Not pregnant or nursing

          -  No prior malignancy except for adequately treated basal cell or squamous cell skin
             cancer, in situ cervical cancer, or other cancer with 5-year disease-free status

          -  No impaired bone marrow reserve, including any of the following:

          -  Hypocellular bone marrow (cellularity ≤ 15%)

          -  Marked ( ≥ 10%) reduction in bone marrow precursors of one or more cell lines
             (granulocytic, megakaryocytic, erythroid) (beyond that which would be expected for the
             patient's age and bone marrow cellularity)

          -  History of failed stem cell collection

          -  No serious, non-malignant disease or infection which, in the opinion of the
             investigator and/or sponsor, would compromise other protocol objectives

          -  At least 3 weeks since all prior therapy (6 weeks for rituximab) and recovered

          -  No prior myeloablative therapies with autologous bone marrow transplantation or
             peripheral blood stem cell rescue

          -  No prior radioimmunotherapy

          -  No prior external beam radiotherapy to > 25% of active bone marrow (involved field or
             regional)

          -  More than 4 weeks since prior major surgery, other than diagnostic surgery

        Exclusion Criteria

        Patients with impaired bone marrow reserve, as indicated by one or more of the following:

          -  Platelet count < 100,000 cells/mm3

          -  Hypocellular bone marrow (cellularity < or = 10%)

          -  Marked (> 10%) reduction in bone marrow precursors of one or more cell lines
             (granulocytic, megakaryocytic, erythroid) (beyond that which would be expected for the
             patient's age and bone marrow cellularity

          -  History of failed stem cell collection

        Prior radioimmunotherapy

        Presence of CNS lymphoma. Patients must not have clinical evidence of central nervous
        system (CNS) involvement by lymphoma.

        Patients with abnormal liver function: total bilirubin > 2.0 mg/dL

        Patients with abnormal renal function: serum creatinine > 2.0 mg/dL or creatinine clearance
        < 50 ml/min.

        Patients who have received prior external beam radiation therapy to > 25% of active bone
        marrow (involved field or regional)

        Patients who have received G-CSF or GM-CSF therapy within 2 weeks prior to treatment

        Serious nonmalignant disease or infection which, in the opinion of the investigator and/or
        the sponsor, would compromise other protocol objectives

        Major surgery, other than diagnostic surgery, within 4 weeks

        Patients with pleural effusion