Donor Natural Killer Cell Infusion, Rituximab, Aldesleukin, and Chemotherapy in Treating Patients With Relapsed Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia
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|ClinicalTrials.gov Identifier: NCT00625729|
Recruitment Status : Terminated (No patients exhibited natural killer cell expansion (primary endpoint).)
First Posted : February 28, 2008
Results First Posted : July 30, 2010
Last Update Posted : December 28, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia Lymphoma||Biological: aldesleukin Biological: allogeneic natural killer cells Biological: rituximab Drug: cyclophosphamide Drug: fludarabine phosphate||Phase 1 Phase 2|
- To determine if allogeneic natural killer (NK) cells infused following chemoimmunotherapy can be safely expanded in vivo with aldesleukin.
- 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.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||MT2007-12 Allogeneic Natural Killer Cells With Rituximab in Patients With CD20 Positive Relapsed Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia. Strategies to Increase Sensitivity of CLL Tumor Cells to Natural Killer Cell-Immune-Mediated Cytolysis|
|Study Start Date :||January 2008|
|Actual Primary Completion Date :||December 2009|
|Actual Study Completion Date :||April 2010|
Experimental: Treated Patients
Patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukemia treated with donor natural killer cells infusion, rituximab, aldesleukin and chemotherapy.
Day 0-14, 10 million international units, 3 times per week for 6 doses
Other Name: IL-2Biological: allogeneic natural killer cells
Day 0 infusion of cells (1.5-8 x 10^7 cells/kg).
Other Name: Natural Killer CellsBiological: rituximab
Administered Day -8, day -1, day +6 and day +13, intravenously (IV) 357 mg/m^2
Other Name: RituxanDrug: cyclophosphamide
60 mg/kg intravenous (IV) on Day -5.
Other Name: CytoxanDrug: fludarabine phosphate
Day -6 through day -2, 25 mg/m^2 intravenous (IV)
Other Name: Fludara
- Number of Patients Exhibiting Natural Killer Cell Expansion [ Time Frame: Day 14 ]Successful natural killer (NK) cell expansion will be defined as an absolute circulating donor-derived NK cell count of >100 cells/μl 14 days after infusion with <5% donor T and B cells in the mononuclear population.
- Number of Patients With Interleukin-15 Production and NK Cell Expansion [ Time Frame: Day 0 ]Correlation of interleukin-15 production at day 0 with natural killer (NK) cells expansion
- Number of Patients With Overall Response [ Time Frame: 3 Months ]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
- Number of Patients Whose Disease Progressed After Treatment [ Time Frame: 6 Months ]Includes patients (with non-Hodgkin leukemia or chronic lymphocytic leukemia) whose disease progressed after treatment.
- Number of Patients With Adequate Natural Killer Cells Infused [ Time Frame: Day 0 ]Incidence of donor products that met release criteria in accordance with FDA regulations (Lot Release Criteria for allogeneic, interleukin-2 (IL-2) activated natural killer (NK) cell products (BB-IND 8847) and the NK cell numbers infused (donor NK cell dose 1.5-8.0 x 10^7/kg).
- Number of Patients With Overall Survival [ Time Frame: 6 Months ]Number of patients alive at 6 months after treatment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00625729
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Veronika Bachanova, MD||Masonic Cancer Center, University of Minnesota|