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

This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), May 2008

Sponsors and Collaborators: Masonic Cancer Center, University of Minnesota
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00625729
  Purpose

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 Intervention Phase
Leukemia
Lymphoma
Drug: aldesleukin
Drug: cyclophosphamide
Drug: fludarabine phosphate
Drug: lymphokine-activated killer cells
Drug: rituximab
Procedure: biomarker analysis
Procedure: pharmacogenomic studies
Procedure: pharmacological study
Phase I
Phase II

MedlinePlus related topics:   Cancer    Leukemia, Adult Acute    Leukemia, Adult Chronic    Lymphoma   

ChemIDplus related topics:   Cyclophosphamide    Fludarabine    Fludarabine monophosphate    Aldesleukin    Rituximab    Salicylsalicylic acid    Sodium salicylate   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, 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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment:   12
Study Start Date:   January 2008
Estimated Primary Completion Date:   January 2010 (Final data collection date for primary outcome measure)

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 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.

  Eligibility
Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

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
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00625729

Locations
United States, Minnesota
Masonic Cancer Center at University of Minnesota     Recruiting
      Minneapolis, Minnesota, United States, 55455
      Contact: Clinical Trials Office - Masonic Cancer Center at University o     612-624-2620        

Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
National Cancer Institute (NCI)

Investigators
Principal Investigator:     Veronika Bachanova, MD     Masonic Cancer Center, University of Minnesota    
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site
 

Study ID Numbers:   CDR0000586667, UMN-2007LS064, MT2007-12, UMN-0707M13561
First Received:   February 26, 2008
Last Updated:   July 23, 2008
ClinicalTrials.gov Identifier:   NCT00625729
Health Authority:   Unspecified

Keywords provided by National Cancer Institute (NCI):
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

Study placed in the following topic categories:
Leukemia, Lymphoid
Lymphoma, Mantle-Cell
Sodium Salicylate
Lymphoma, Follicular
Lymphoma, small cleaved-cell, diffuse
Cyclophosphamide
Lymphoma, large-cell, immunoblastic
Lymphoma, large-cell
Lymphomatoid granulomatosis
Burkitt's lymphoma
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, T-Cell
Lymphoma, Large-Cell, Immunoblastic
Waldenstrom macroglobulinemia
Lymphoma
Chronic lymphocytic leukemia
Lymphomatoid Granulomatosis
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Rituximab
Leukemia, B-cell, chronic
Salicylsalicylic acid
Fludarabine monophosphate
Lymphoblastic lymphoma
Mantle cell lymphoma
Recurrence
Lymphatic Diseases
Waldenstrom Macroglobulinemia
Aldesleukin

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Anti-HIV Agents
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Immune System Diseases
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Anti-Retroviral Agents
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on August 29, 2008




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