A Phase II Study of Allo-HCT for B-Cell NHL Using Zevalin, Fludarabine and Melphalan
Condition: Graft Versus Host Disease; Leukemia; Lymphoma
MeSH terms: Lymphoma; Leukemia; Graft vs Host Disease
Intervention: rituximab; fludarabine phosphate; melphalan; sirolimus; tacrolimus; allogeneic hematopoietic stem cell transplantation; indium In 111 ibritumomab tiuxetan; yttrium Y 90 ibritumomab tiuxetan; laboratory biomarker analysis
Intervention description: Given IV; Given IV; Given IV; Given PO; Given PO or IV; Undergo APBSCT; Given IV; Given IV; Correlative Studies
Intervention MeSH terms: Sirolimus; Rituximab; Fludarabine; Fludarabine phosphate; Melphalan; Tacrolimus; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Maximum age: 69 Years
Healthy volunteers: No
Keywords: graft versus host disease; 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 I grade 1 follicular lymphoma; stage I grade 2 follicular lymphoma; stage I 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; 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; Waldenstrom macroglobulinemia; contiguous stage II marginal zone lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; noncontiguous stage II marginal zone lymphoma; recurrent marginal zone lymphoma; stage I marginal zone lymphoma; stage III marginal zone lymphoma; stage IV marginal zone lymphoma; B-cell chronic lymphocytic leukemia; refractory chronic lymphocytic leukemia; stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; contiguous stage II mantle cell lymphoma; noncontiguous stage II mantle cell lymphoma; recurrent mantle cell lymphoma; stage I mantle cell lymphoma; stage III mantle cell lymphoma; stage IV mantle 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 small lymphocytic lymphoma; noncontiguous stage II small lymphocytic lymphoma; recurrent small lymphocytic lymphoma; stage I small lymphocytic lymphoma; stage III small lymphocytic lymphoma; stage IV small lymphocytic lymphoma

Summary:

      RATIONALE: Giving monoclonal antibody therapy, radioimmunotherapy, and chemotherapy before a
      donor stem cell transplant helps stop the growth of cancer cells and helps stop the patient's
      immune system from rejecting the donor's stem cells. When the stem cells from a related donor
      that do not exactly match the patient's blood, are infused into the patient, they may help
      the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
      Sometimes the transplanted cells from a donor can also make an immune response against the
      body's normal cells. Giving tacrolimus and sirolimus before and after transplant may stop
      this from happening.

      PURPOSE: This phase II trial is studying the side effects and how well giving indium In 111
      ibritumomab tiuxetan and yttrium y 90 ibritumomab tiuxetan together with rituximab,
      fludarabine, melphalan, and donor stem cell transplant works in treating patients with B-cell
      non-Hodgkin lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  6/6/human leukocyte antigen (HLA) matched sibling donor or related donor, or
             acceptable matched unrelated donor

          -  Biopsy (Bx) proven diagnosis of LG (including small lymphocytic lymphoma [SLL]/chronic
             lymphocytic leukemia [CLL], lymphoplasmacytic lymphoma, marginal zone,
             mucosa-associated lymphoid tissue [MALT] lymphoma and follicular lymphoma [FL] grade 1
             and 2), IG (FL grade 3 and DLCL) or MCL NHL

          -  Prior demonstrated monoclonal CD20+ malignant B-Cell population in lymph nodes and/or
             BM Bx specimen

          -  LG NHL; must have relapsed after achieving a complete response (CR) or partial
             response (PR) to prior therapy or have never responded to prior therapy, including
             chemotherapy and/or MAb therapy

          -  MCL NHL in any disease state

          -  Other aggressive B-cell lymphomas (excluding Burkitt lymphoma or Burkitt-like
             lymphoma) having had at least one relapse or having been refractory to chemotherapy

          -  Bone marrow (BM) aspiration and Bx ( =< 42 days prior to imaging dose) which show <
             25% lymphomatous involvement of total cellularity; in CLL, peripheral lymphocyte count
             < 5000/mm^3

          -  Salvage chemotherapy/MAbs to reduce BM lymphomatous involvement and reduce disease
             bulk allowed

          -  Normal renal function test with serum creatinine of =< 1.5 mg/dl, or a creatinine
             clearance of >= 60 ml/min

          -  Adequate pulmonary function as measured by forced expiratory volume in one second
             (FEV1) > 65% of predicted measured, or a diffusing capacity of carbon monoxide (DLCO)
             >= 50% of predicted measured

          -  Cardiac Ejection fraction of > 50% by Echocardiogram (ECHO) or multi gated acquisition
             (MUGA)

          -  Adequate liver function tests with a bilirubin of =< 1.5 x normal and serum glutamic
             oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) =< 2 x
             normal

          -  Negative Human Immunodeficiency Virus (HIV) antibody

          -  Karnofsky Performance Status (KPS) > 80

          -  No active Central Nervous System (CNS) disease or prior history of CNS disease

          -  Involved field External Beam Therapy (EBT) to area excluding lung, heat, liver, and
             kidney allowed, but evaluated on a case-by-case basis

          -  Recovery from last therapy and therapy dose (Y-90 Zevalin) must be >= 4 weeks from
             prior systemic chemotherapy

          -  DONOR: Age < 75 years

          -  DONOR: HLA genotypically identical related donor or acceptable matched unrelated donor

          -  DONOR: Must consent to G-CSF administration and leukapheresis for matched sibling
             donor, but for unrelated donor, the donor will sign a standard consent for donation at
             their designated donor or collection center

          -  DONOR: Must have adequate veins for leukapheresis or agree to placement of a Central
             Venous Catheter (CVC [femoral, subclavian])

        Exclusion Criteria:

          -  Presence of Human Anti-Zevalin Antibody (HAZA)

          -  Prior radioimmunotherapy (RIT)

          -  Prior AHSCT; but prior aHSCT is allowed; prior fractionated total body irradiation
             (FTBI) in the conditioning regimen will be evaluated on an individual basis

          -  Prior malignancy, except for: adequately treated basal cell or squamous cell skin
             cancer; adequately treated noninvasive carcinomas; or other cancer from which the
             patient has been disease-free for at least 5 years; myelodysplastic syndromes (MDS) is
             excluded from this criterion

          -  Active evidence of Hepatitis B or C infection; hepatitis B surface antigen positive

          -  Total peripheral lymphocyte count > 5,000/mm^3 if SLL/CLL

          -  Burkitt lymphoma or Burkitt-like lymphoma

          -  DONOR: Age < 12 years

          -  DONOR: Identical twin

          -  DONOR: Pregnancy

          -  DONOR: HIV infection

          -  DONOR: Inability to achieve adequate venous access

          -  DONOR: Known allergy to G-CSF

          -  DONOR: Current serious systemic illness or any disease that may preclude the use of
             G-CSF (eg, recent thromboembolic event); for unrelated donors, considered ineligible
             by National Marrow Donor Program (NMDP) donor evaluation center