Umbilical Cord Blood NK Cells, Rituximab, High-Dose Chemotherapy, and Stem Cell Transplant in Treating Patients With Recurrent or Refractory B-Cell Non-Hodgkin's Lymphoma
Condition: Mantle Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Indolent Adult Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Indolent Adult Non-Hodgkin Lymphoma
MeSH terms: Lymphoma; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Recurrence
Study type: Interventional
Phase: Phase 2

Summary: 
      This phase II trial studies the side effects of cord blood-derived expanded allogeneic
      natural killer cells (umbilical cord blood natural killer [NK] cells), rituximab, high-dose
      chemotherapy, and stem cell transplant in treating patients with B-cell non-Hodgkin's
      lymphoma that has come back (recurrent) or that does not respond to treatment (refractory).
      Immune system cells, such as cord blood-derived expanded allogeneic natural killer cells, are
      made by the body to attack foreign or cancerous cells. Immunotherapy with rituximab, may
      induce changes in body's immune system and may interfere with the ability of tumor cells to
      grow and spread. Drugs used in chemotherapy, such as carmustine, cytarabine, etoposide,
      lenalidomide, melphalan, and rituximab, work in different ways to stop the growth of cancer
      cells, either by killing the cells, by stopping them from dividing, or by stopping them from
      spreading. A stem cell transplant using stem cells from the patient or a donor may be able to
      replace blood-forming cells that were destroyed by chemotherapy used to kill cancer cells.
      The donated stem cells may also replace the patient's immune cells and help destroy any
      remaining cancer cells. Giving cord blood-derived expanded allogeneic natural killer cells,
      rituximab, high-dose chemotherapy, and stem cell transplant may work better in treating
      patients with recurrent or refractory B-cell non-Hodgkin's lymphoma.
    

Detailed description: 
      PRIMARY OBJECTIVE:

      I. To establish the safety of this treatment by determining its treatment-related mortality
      (TRM) within 30 days.

      SECONDARY OBJECTIVES:

      I. To estimate the relapse-free survival (RFS). II. To estimate the overall survival (OS).
      III. To quantify duration of infused allogeneic umbilical cord blood (UCB)-derived natural
      killer (NK) cells in the recipient.

      OUTLINE:

      PREPARATIVE REGIMEN: Patients receive carmustine intravenously (IV) over 2 hours on day -12,
      etoposide IV twice daily (BID) over 3 hours on days -11 to -8, cytarabine IV BID over 1 hour
      on days -11 to -8, melphalan IV over 30 minutes on day -7, and lenalidomide orally (PO) once
      daily (QD) on days -7 to -2 in the absence of disease progression or unacceptable toxicity.
      Patients who are CD20+ also receive rituximab IV over 3 hours on days -13 and -7.

      NK-CELL INFUSION: Patients receive cord blood-derived expanded allogeneic NK cells IV over 1
      hour on day -5 in the absence of disease progression or unacceptable toxicity.

      STEM CELL TRANSPLANT: Patients undergo stem cell transplant IV over 30-60 minutes on day 0 in
      the absence of disease progression or unacceptable toxicity.

      POST-TRANSPLANT: Patients receive filgrastim subcutaneously (SC) QD beginning on day +5.
      Treatment continues until white blood cell count recovers in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30, 100, and 180 days.
    

Intervention name(s): Autologous Hematopoietic Stem Cell Transplantation; Carmustine; Cord Blood-derived Expanded Allogeneic Natural Killer Cells; Cytarabine; Etoposide; Filgrastim; Lenalidomide; Melphalan; Rituximab
Intervention type(s): Procedure; Drug; Biological; Drug; Drug; Biological; Drug; Drug; Biological
Intervention description(s): Undergo stem cell transplant; Given IV; Given IV; Given IV; Given IV; Given SC; Given PO; Given IV; Given IV
Other intervention name(s): Autologous Hematopoietic Cell Transplantation; autologous stem cell transplantation; BCNU; Becenum; Becenun; BiCNU; Bis(chloroethyl) Nitrosourea; Bis-Chloronitrosourea; Carmubris; Carmustin; Carmustinum; FDA 0345; N,N''-Bis(2-chloroethyl)-N-nitrosourea; Nitrourean; Nitrumon; SK 27702; SRI 1720; WR-139021; Allogeneic CB-derived Ex vivo-expanded NK Cells; CB-derived Expanded Allogeneic NK Cells; UCB-derived Expanded Allogeneic NK Cells; Umbilical Cord Blood-derived Expanded Allogeneic Natural Killer Cells; .beta.-Cytosine arabinoside; 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-.beta.-D-Arabinofuranosylcytosine; 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-Beta-D-arabinofuranosylcytosine; 1.beta.-D-Arabinofuranosylcytosine; 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-; 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-; Alexan; Ara-C; ARA-cell; Arabine; Arabinofuranosylcytosine; Arabinosylcytosine; Aracytidine; Aracytin; Aracytine; Beta-cytosine Arabinoside; CHX-3311; Cytarabinum; Cytarbel; Cytosar; Cytosine Arabinoside; Cytosine-.beta.-arabinoside; Cytosine-beta-arabinoside; Erpalfa; Starasid; Tarabine PFS; U 19920; U-19920; Udicil; WR-28453; Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; G-CSF; Neupogen; r-metHuG-CSF; Recombinant Methionyl Human Granulocyte Colony Stimulating Factor; rG-CSF; Tevagrastim; CC-5013; CC5013; CDC 501; Revlimid; Alanine Nitrogen Mustard; CB-3025; L-PAM; L-Phenylalanine Mustard; L-sarcolysin; L-Sarcolysin Phenylalanine mustard; L-Sarcolysine; Melphalanum; Phenylalanine Mustard; Phenylalanine nitrogen mustard; Sarcoclorin; Sarkolysin; WR-19813; ABP 798; BI 695500; C2B8 Monoclonal Antibody; Chimeric Anti-CD20 Antibody; CT-P10; IDEC-102; IDEC-C2B8; IDEC-C2B8 Monoclonal Antibody; MabThera; Monoclonal Antibody IDEC-C2B8; PF-05280586; Rituxan; Rituximab ABBS; Rituximab Biosimilar ABP 798; Rituximab Biosimilar BI 695500; Rituximab Biosimilar CT-P10; Rituximab Biosimilar GB241; Rituximab Biosimilar IBI301; Rituximab Biosimilar JHL1101; Rituximab Biosimilar PF-05280586; Rituximab Biosimilar RTXM83; Rituximab Biosimilar SAIT101; rituximab biosimilar TQB2303; rituximab-abbs; RTXM83; Truxima
Intervention MeSH terms: Cytarabine; Rituximab; Antineoplastic Agents, Immunological; Etoposide; Lenalidomide; Etoposide phosphate; Melphalan; Mechlorethamine; Carmustine; Podophyllotoxin; Nitrogen Mustard Compounds; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Lenograstim
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment