• 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 pharmacodynamics and pharmacogenomics with NK cell expansion and disease response [ Designated as safety issue: No ]

• 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 CLL [ 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 ]

RATIONALE: Aldesleukin may stimulate natural killer cells to kill cancer cells. Treating natural killer cells with aldesleukin in the laboratory may help the natural killer cells kill more cancer cells when they are put back in the body. Giving monoclonal antibodies, such as rituximab, and chemotherapy drugs, such as fludarabine and cyclophosphamide, before a donor natural killer cell infusion helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells.

PURPOSE: This phase I/II trial is studying how well giving rituximab and chemotherapy followed by a donor natural killer cell infusion that has been treated in the laboratory with aldesleukin followed by aldesleukin works in treating patients with non-Hodgkin lymphoma or chronic lymphocytic leukemia.

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 28 days 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 periodically for correlative laboratory studies. Patients with CLL also undergo bone marow aspiration periodically for correlative laboratory studies.

After completion of study treatment, patients are followed periodically for up to 1 year.

• Leukemia
• Lymphoma

• Biological: aldesleukin
• Biological: lymphokine-activated killer cells
• Biological: rituximab
• Drug: cyclophosphamide
• Drug: fludarabine phosphate
• Other: laboratory biomarker analysis
• Other: pharmacogenomic studies
• Other: pharmacological study

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 purine analogs) 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
• FEV_1 > 50% corrected
• LVEF > 40%
• 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 NOTE: *The hematologic requirements are waived for patients with inadequate counts due to known bone marrow involvement by lymphoma who are otherwise eligible

PRIOR CONCURRENT THERAPY:

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