Donor Natural Killer Cell Infusion, Rituximab, Aldesleukin, and Chemotherapy in Treating Patients With Relapsed Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia

This is an interventional treatment trial for Leukemia focused on measuring recurrent adult grade III lymphomatoid granulomatosis, adult nasal type extranodal NK/T-cell lymphoma, Waldenstrom macroglobulinemia, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, refractory chronic lymphocytic leukemia Read More

Inclusion Criteria:

• Patient 18 years or older with a diagnosis of non-Hodgkin Lymphoma or chronic lymphocytic leukemia (NHL or CLL) and one of the following:

  • Progression of NHL following at least 2 prior chemotherapy regimens, (must contain rituximab for all NHL and fludarabine for follicular NHL) defined as:

    • failure to achieve partial remission (PR) with the last chemotherapy
    • disease progression within 6 months following last chemotherapy
  • Progression of CLL/SLL (small lymphocytic lymphoma) following at least 2 prior chemotherapy regimens (containing purine analogs ) in stage Rai III or IV or symptomatic disease.
  • Relapsed NHL or CLL following stem cell transplantation for whom the option of donor lymphocyte infusion is not available or clinically indicated (e.g. recipients of autologous or umbilical cord blood [UCB] transplants).
• Available related HLA-haploidentical (human leukocyte antigen) natural killer (NK) cell adult donor by at least Class I serologic typing
• Karnofsky performance status > 60%
• Measurable disease based on modified Response Evaluation Criteria In Solid Tumors (RECIST)

• Have acceptable organ function as defined within 28 days of enrollment:

  • Hematologic: platelets ≥ 80,000 x 10^9/L; hemoglobin ≥ 9g/dL, unsupported by transfusions; absolute neutrophil count (ANC) ≥ 1000 x 10^9/L, unsupported by granulocyte-colony stimulating factor or granulocyte-macrophage colony-stimulating factor (G-CSF or GM-CS)F for 10 days or Neulasta for 21 days - the hematologic requirements are waived for patients with inadequate counts due to known bone marrow involvement by lymphoma who are otherwise eligible
  • Renal: glomerular filtration rate (GFR) > 50 ml/min
  • Hepatic: alanine aminotransferase (ALT), aspartate aminotransferase (AST) < 3 x upper limit of normal and total bilirubin <3 mg/dl
  • Pulmonary function: >50% corrected carbon monoxide diffusing capacity (DLCO) and Forced Expiratory Volume in the first second (FEV1)
  • Cardiac: no symptoms of uncontrolled cardiac disease, left ventricular ejection fraction >40%
• Off prednisone or other immunosuppressive medications for at least 3 days prior to Day 0
• Women of childbearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment.
• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care.

Exclusion Criteria:

• Pregnant or lactating. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy. Women of childbearing age must use appropriate contraceptive method.
• Active central nervous system (CNS) lymphoma/leukemia
• Active serious infection (pulmonary infiltrates or lesions are allowed only after the appropriate diagnostic testing is negative for infection or appropriate therapy was initiated for probable infection)
• Pleural effusion - large enough to be detectable on the chest x-ray
• Allergy to rituximab or IL-2
• Human immunodeficiency virus (HIV) and associated non-Hodgkins lymphoma (NHL)
• Active concurrent malignancy (except skin cancer) requiring systemic therapy in the past 2 years
• Epstein-Barr virus (EBV) post-transplant lymphoproliferative disorder
• Positive hepatitis B surface antigen (HBsAg). If Hepatitis B core antibody (HBcAb) is positive, Hepatitis B deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR) will be evaluated. Positive anti HBcAb and undetectable viral load does not exclude the patient.
• Any experimental therapy in the past 30 days

Donor Selection:

• Related donors (sibling, parent, offspring, parent or offspring of an HLA identical sibling) ≥ age 18 years
• Able and willing to undergo lymphapheresis
• HLA-haploidentical donor/recipient match. If time permits and multiple donors are available, preference will be given to the Killer-cell Immunoglobulin-like Receptors (KIR) ligand mismatched donor (as predicted by HLA typing).
• HIV-1, HIV-2 negative, Human T-lymphotropic virus Type I (HTLV-1), HTLV-2 negative, West Nile virus (WNV) negative, Hepatitis B and C negative

• Adequate organ function defined as:

  • Hematologic: CBC/diff/platelet count near normal limits,
  • Hepatic: ALT < 2 x upper limit of normal,
• Not pregnant or lactating
• In general good health as determined by the study physician
• Able to give informed consent