Yttrium Y 90 Ibritumomab Tiuxetan, Etoposide, Cyclophosphamide, and an AHSCT in Non-Hodgkin's Lymphoma Patients

RATIONALE: Radiolabeled monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can find cancer cells and carry tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as etoposide and cyclophosphamide, work in different ways to kill cancer cells or stop them from growing. Giving radiolabeled monoclonal antibodies together with etoposide and cyclophosphamide before a peripheral blood stem cell transplant may be an effective treatment for non-Hodgkin lymphoma.

PURPOSE: This phase I/II trial is studying the side effects and best dose of yttrium Y 90 ibritumomab tiuxetan when given together with etoposide and cyclophosphamide followed by an autologous stem cell transplant and to see how well it works in treating patients with non-Hodgkin lymphoma.

OBJECTIVES:

* To evaluate the safety and efficacy of a new preparative regimen of yttrium Y 90 ibritumomab tiuxetan in combination with high-dose etoposide and cyclophosphamide followed by autologous stem cell transplantation (ASCT) for treatment of patients with poor-risk, relapsed, or refractory non-Hodgkin lymphoma (NHL).
* To determine the maximum tolerated dose of yttrium Y 90 ibritumomab tiuxetan which can be given with high-dose etoposide and high-dose cyclophosphamide followed by ASCT in patients with NHL.
* To perform dosimetry study to estimate the radiation dose delivered to the tumor and normal organs.
* To evaluate the short-term and long-term complications of this new preparative regimen.

OUTLINE: This is a phase I does-escalation study of yttrium Y 90 ibritumomab tiuxetan followed by an open-label phase II study.

* Preparation for transplantation: Peripheral blood stem cells (PBSCs) are collected via leukapheresis. Samples are analyzed by cytogenetic studies, immunophenotyping, and gene rearrangement. Patients with an adequate number of collected CD34-positive cells (≥ 3 times 10\^6 /kg) proceed to radioimmunotherapy.
* Radioimmunotherapy: Patients receive yttrium Y 90 ibritumomab tiuxetan IV on days -21 and -14. Patients undergo bone marrow biopsy and dose estimation on day -7.
* Chemotherapy: Patients receive etoposide IV on day -4 and cyclophosphamide IV over 2 hours on day -2.
* Transplantation: Patients undergo reinfusion of PBSCs on day 1.
* Growth factor therapy: Patients receive filgrastim (G-CSF) IV beginning on day 1 and continuing until blood counts recover.

Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Biopsy proven diagnosis of low- or intermediate-grade\* non-Hodgkin lymphoma (NHL) including any of the following:

  * Follicular small cleaved
  * Follicular mixed
  * Follicular large cell
  * Diffuse small cleaved
  * Diffuse mixed
  * Diffuse large cell
  * Immunoblastic (working formulation B, C, D, E, F, G and H) NOTE: \*A new classification scheme for adult non-Hodgkin lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low-", "intermediate-", or "high-" grade lymphoma. However, this protocol uses the former terminology.
* Mantle cell and transformed low-grade lymphomas allowed
* Demonstrated monoclonal CD20-positive B-cell population in lymph nodes and/or bone marrow
* Favorable biodistribution on imaging dose
* Patient either relapsed after achieving a complete (CR) or partial response (PR) to prior therapy, never responded to prior therapy, or has poor-risk disease

  * Sensitivity of disease based on 1 of the following:

    * Induction failure: patients who did not achieve a CR or PR from induction chemotherapy
    * Resistant relapse: patients who did not achieve a CR or PR from the most recent standard salvage chemotherapy
    * Sensitive relapse: patients who did achieve a CR or PR from the most recent standard salvage chemotherapy
  * Poor-risk disease defined as any of the following:

    * Age-adjusted International Prognostic Index (IPI) High- (3 risk factors) or High-Intermediate (2 risk factors) based on the following risk factors:

      * Stage III-IV disease
      * Elevated serum lactate dehydrogenase level
      * ECOG performance status 2-4
    * Patients with aggressive NHL including mantle cell lymphoma and who required 2 different induction chemotherapy regimens to achieve a CR/PR
    * Patients with B-cell NHL and who failed to achieve a CR after adequate induction chemotherapy regimen(s)
* Patients must have bone marrow aspiration and biopsy within 42 days before salvage chemotherapy or stem cell collection which show ≤ 10% lymphomatous involvement of total cellularity
* Normal cytogenetic study on bone marrow (prior to salvage chemotherapy or stem cell collection)

  * Cytogenetic study on peripheral blood is acceptable if bone marrow biopsy has already been done and shows no sign of myelodysplastic syndrome (MDS) or lymphoma and a repeat bone marrow is deemed unnecessary by attending physician
* No active or prior history of CNS diseases
* No human anti-mouse antibody (HAMA) or human anti-chimeric antibody

PATIENT CHARACTERISTICS:

* ECOG performance status (PS) 0-1 or Karnofsky PS 80-100%
* Platelet count normal
* Serum creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 60 mL/min
* FEV_1 \> 65% of predicted or DLCO ≥ 50% of predicted
* LVEF \> 50% by ECHO or MUGA scan
* Bilirubin ≤ 1.5 times normal
* SGOT or SGPT ≤ 2 times normal
* HIV antibody-negative
* No prior malignancy except for adequately treated basal cell or squamous cell skin cancer, adequately treated noninvasive carcinoma, or other cancer from which the patient has been disease-free for at least five years
* No active evidence of hepatitis B or C infection
* No hepatitis B surface antigen positivity
* No history of alcohol abuse
* Body weight ≤ 250 pounds

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* Patients who have received involved field external beam therapy to area excluding lung, heart, liver and kidney are allowed, but will be evaluated on a case-by-case basis
* Patients must have recovered from last therapy and should be at least four weeks from prior radiation or chemotherapy
* No prior radioimmunotherapy
* No prior bone marrow transplantation