Clinical trial NCT00625729
Conditions: Leukemia Lymphoma
Keywords: 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
Sponsor: Masonic Cancer Center, University of Minnesota
Start date: 2008-01-01; Completion date: 2010-04-01
Enrollment: 6 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
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 intravenously (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 absolute neutrophil count (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 chronic lymphocytic leukemia (CLL) also undergo bone marrow aspiration periodically for correlative laboratory studies.

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

Arms: arm 1: Patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukemia treated with donor natural killer cells infusion, rituximab, aldesleukin and chemotherapy.
Interventions: intervention 1: aldesleukin intervention 2: allogeneic natural killer cells intervention 3: rituximab intervention 4: cyclophosphamide intervention 5: fludarabine phosphate
Intervention descriptions: intervention 1: Day 0-14, 10 million international units, 3 times per week for 6 doses intervention 2: Day 0 infusion of cells (1.5-8 x 10\^7 cells/kg). intervention 3: Administered Day -8, day -1, day +6 and day +13, intravenously (IV) 357 mg/m\^2 intervention 4: 60 mg/kg intravenous (IV) on Day -5. intervention 5: Day -6 through day -2, 25 mg/m\^2 intravenous (IV)

Protocol documents: