Yttrium-90 Ibritumomab Tiuxetan Plus High-Dose BEAM Followed By ASCT For Relapsed B-Cell Non-Hodgkin Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma
Intervention: rituximab; carmustine; cytarabine; etoposide; melphalan; ASCT; yttrium Y 90 ibritumomab tiuxetan
Intervention description: Given IV; Given IV; Given IV; Given IV; Given IV; Undergo autologous peripheral blood stem cell transplant; Given IV
Intervention MeSH terms: Cytarabine; Rituximab; Etoposide; Etoposide phosphate; Melphalan; Carmustine; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 122.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent mantle cell lymphoma; stage III mantle cell lymphoma; stage IV mantle cell lymphoma; recurrent adult diffuse large cell lymphoma; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell 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; stage III adult immunoblastic large cell lymphoma; stage IV adult immunoblastic large cell lymphoma; recurrent adult immunoblastic large cell lymphoma

Summary:

      This phase II clinical trial studies how well yttrium Y 90 ibritumomab tiuxetan, rituximab,
      and high-dose chemotherapy followed by peripheral blood stem cell transplant in treating
      patients with relapsed B-cell non-Hodgkin lymphoma. Monoclonal antibodies, such as yttrium Y
      90 ibritumomab tiuxetan and 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 can find tumor
      cells and carry tumor-killing substances to them without harming normal cells. Giving
      monoclonal antibody therapy, radioimmunotherapy (RIT), and high-dose combination chemotherapy
      before a peripheral blood stem cell transplant may be an effective treatment for non-Hodgkin
      lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All patients must have biopsy proven diagnosis of low- and intermediate-grade
             non-Hodgkin lymphoma (NHL) working formulation B, C,D, E, F, and G; including mantle
             cell lymphoma; patients with transformed lymphoma are also eligible

          -  Demonstrated monoclonal CD20 positive b-cell population in lymph nodes and/or bone
             marrow

          -  Patients must have relapsed after achieving a complete or partial response to prior
             therapy, have never responded to prior therapy or have poor risk disease

          -  Patients with prior bone marrow involvement must have bone marrow aspiration and
             biopsy within 60 days prior to stem cell collection which shows =< 10% lymphomatous
             involvement of total cellularity; alternatively, patients with prior bone marrow
             involvement should have a normal bone marrow study which shows =< 10% lymphomatous
             involvement within 28 days before salvage chemotherapy

          -  Normal renal function test with serum creatinine of < upper limit of normal (ULN), and
             a creatinine clearance of >= 60 ml/min (measured or calculated)

          -  Adequate pulmonary function as measured by forced expiratory volume in 1 second (FEV1)
             > 60% of predicted measured, or a diffusion capacity of carbon monoxide (DLCO) >= 50%
             of predicted measured

          -  Cardiac ejection fraction of > 50% by echocardiogram or multi gated acquisition (MUGA)
             scan; the left ventricular ejection fraction (LVEF) from the prestudy echocardiogram
             (ECHO) or MUGA may be used for eligibility purposes, even if the prestudy stress test
             indicated a lower LVEF

          -  Adequate liver function tests with a bilirubin of =< 1.5 x ULN and serum glutamic
             oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) =< 2 x
             ULN

          -  Negative human immunodeficiency virus antibody

          -  Eastern Cooperative Oncology Group (ECOG) performance status = 0 or 1; karnofsky
             performance status (KPS) >= 80

          -  No active central nervous system (CNS) disease or prior history of CNS disease

          -  Patients must have recovered from last therapy and should be at least four weeks from
             prior radiation or systemic chemotherapy on the day of administration of Y2B8

          -  After the last systemic therapeutic chemotherapy (Cytoxan, administered only for stem
             cell mobilization is not considered therapeutic) and prior to initiation of high dose
             treatment, the patient should have a baseline computed tomography (CT) scan and
             positron emission tomography (PET) scan done; an fluorodeoxyglucose-computed
             tomography (FDG/CT) scan is sufficient, however, is clinically indicated, an
             additional diagnostic CT may be ordered; exception: if scans were done and were
             negative for disease just prior to priming chemotherapy (therapeutic or
             nontherapeutic) and subsequent stem cell harvest, they do not need to be repeated
             prior to initiation of high dose treatment

        Exclusion Criteria:

          -  Presence of human anti-Zevalin antibody (HAZA)

          -  Prior radioimmunotherapy

          -  Failure to collect adequate number of CD34+ cells >= 3 x 10^6/kg

          -  Abnormal cytogenetic study not related to the underlying lymphoma on the bone marrow
             aspirate sample prior to stem cell collection; if cytogenetics were not performed on
             the marrow aspirate prior to stem cell collection, cytogenetics on the peripheral
             blood may be performed

          -  Prior bone marrow transplantation

          -  Prior malignancy except for:

               -  Adequately treated basal cell or squamous cell skin cancer

               -  Adequately treated noninvasive carcinoma

               -  Other cancer from which the patient has been disease-free for at least five years

          -  Active evidence of Hepatitis B or C infection; Hepatitis B surface antigen positive

          -  Patients who have had prior radiation to the lung will be excluded from the study,
             although mediastinal irradiation will be permitted if minimal lung is in the treatment
             volume

          -  Patients who have received > 500cGy radiation to the kidneys will be excluded from the
             study

          -  Patients who are pregnant or lactating