• Safety of expanding donor-derived natural killer (NK) cells to > 100 cells/μL by day 14 after fludarabine, cyclophosphamide, and rituximab [ Designated as safety issue: Yes ]
  

• Correlation of interleukin-15 production at day 0 with NK cells expansion [ Designated as safety issue: No ]
  
• Overall response (complete remission plus partial remission) rate at 3 months, as defined by International Working Group for non-Hodgkin lymphoma and NCI Working Group guidelines for chronic lymphocytic leukemia [ Designated as safety issue: No ]
  
• Time to progression and overall survival [ Designated as safety issue: No ]
  
• Quantitative and qualitative toxicities [ Designated as safety issue: Yes ]
  
• Incidence of donor products that do not meet release criteria and the NK cell numbers infused [ Designated as safety issue: No ]
  
• Correlation of clinical response rate with FcG receptor 3A genotype (CD16) on donor NK cells, donor/recipient KIR ligand matching status, and NK cells phenotype and function (ADCC) [ Designated as safety issue: No ]
  
• Correlation of pharmacodynamic and pharmacogenomic with NK cell expansion and disease response [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• To determine if allogeneic natural killer (NK) cells infused following chemoimmunotherapy can be safely expanded in vivo with aldesleukin.

Secondary

• To determine if interleukin-15 production at day 0 correlates with NK cells expansion.
• To determine overall response rate at 3 months.
• To determine time to progression and overall survival.
• To characterize the quantitative and qualitative toxicities of this treatment plan.
• To determine the incidence of donor products that do not meet release criteria and the NK cell numbers infused.
• To correlate clinical response with donor/recipient KIR ligand matching status, FcG receptor 3A genotype, and NK cells phenotype and function
• To determine pharmacodynamic and pharmacogenomic markers and correlate them with NK cell expansion and disease response.

OUTLINE:

• Conditioning regimen: Patients receive rituximab IV over 6-8 hours on days -8, -1, 6, and 13; fludarabine IV on days -6 to -2; and cyclophosphamide IV on day -5.
• Allogeneic natural killer (NK) cell administration: Patients receive aldesleukin-activated haploidentical NK cells IV over less than 1 hour on day 0. Within 4 hours after allogeneic NK cell infusion, patients receive aldesleukin subcutaneously (SC) 3 times a week for 6 doses. Patients also receive filgrastim (G-CSF) SC beginning on day 14 and continuing until ANC is > 2,500/mm³ for 2 consecutive days.

Patients who achieve a complete or partial response at 3 months are eligible for allogeneic stem cell transplantation. Patients who achieve initial response at 3 months, clinically benefit from treatment, but subsequently relapse are eligible for retreatment provided all eligibility criteria are met.

Blood samples are collected before treatment on days -8, 0, 7, 14, and 28, and at months 2 and 3 for correlative studies.

After completion of study treatment, patients are followed monthly for 3 months and then every 3 months for up to 1 year.

DISEASE CHARACTERISTICS:

• Diagnosis of CD20-positive non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL), meeting 1 of the following criteria:

  • Progression of NHL after at least 2 prior chemotherapy regimens*, defined by 1 of the following:

    • Failure to achieve partial remission (PR) with the last chemotherapy
    • Disease progression within 6 months after last chemotherapy
  • Progression of CLL or small lymphocytic leukemia following at least 2 prior chemotherapy regimens (containing fludarabine) in stage Rai III or IV or symptomatic disease
  • Relapsed NHL or CLL after 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 transplantations) NOTE: *Must have contained rituximab (for patients with any NHL) and fludarabine (for patients with follicular NHL)
• Measurable disease
• No active CNS lymphoma/leukemia
• No pleural effusion large enough to be detectable by chest x-ray
• No HIV-associated NHL
• No Epstein-Barr virus post-transplant lymphoproliferative disorder
• Available related HLA-haploidentical related natural killer cell donor (by at least Class I serologic typing)

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• Platelet count ≥ 80,000/mm³
• Hemoglobin ≥ 9 g/dL (unsupported by transfusions)
• ANC ≥ 1,000/mm³ (unsupported by filgrastim [G-CSF] or sargramostim [GM-CSF] for 10 days or pegfilgrastim [Neulasta] for 21 days)
• Glomerular filtration rate > 50 mL/min
• ALT and AST < 3 times upper limit of normal
• Total bilirubin < 3 mg/dL
• DLCO > 50% corrected (testing required only if symptomatic or prior known impairment)
• FEV_1 > 50% corrected (testing required only if symptomatic or prior known impairment)
• LVEF > 40% (testing required only if symptomatic or prior known impairment)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Hepatitis B surface antigen negative
• Hepatitis B core antibody negative
• No symptoms of uncontrolled cardiac disease
• No 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)
• No allergy to rituximab or aldesleukin
• No active concurrent malignancy (except skin cancer) requiring systemic therapy in the past 2 years

PRIOR CONCURRENT THERAPY:

• At least 3 days since prior prednisone or other immunosuppressive medications
• At least 30 days since prior experimental therapy