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

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

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

Resource links provided by NLM:

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

Drug Information available for: Cyclophosphamide Fludarabine Fludarabine monophosphate Aldesleukin Rituximab

U.S. FDA Resources

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 2011 (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

Additional Information:

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

No publications provided

Responsible Party:	Masonic Cancer Center at University of Minnesota ( Veronika Bachanova )
Study ID Numbers:	CDR0000586667, UMN-2007LS064, MT2007-12, UMN-0707M13561
Study First Received:	February 26, 2008
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00625729 History of Changes
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:

Antimetabolites
Leukemia, Lymphoid
Immunologic Factors
Lymphoma, Mantle-Cell
Lymphoma, Follicular
Mantle Cell Lymphoma
Cyclophosphamide
Lymphoblastic Lymphoma
Follicular Lymphoma
Lymphoma, Large-cell, Immunoblastic
Lymphoma, Small Cleaved-cell, Diffuse
Leukemia
Anti-Retroviral Agents
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, T-Cell

Lymphoma, Large-Cell, Immunoblastic
Leukemia, B-cell, Chronic
Lymphoma, Large-cell
Alkylating Agents
Lymphoma
Lymphomatoid Granulomatosis
Lymphoma, Large B-Cell, Diffuse
Anti-HIV Agents
Immunoproliferative Disorders
Rituximab
Fludarabine monophosphate
Antiviral Agents
Immunosuppressive Agents
Recurrence
Burkitt's Lymphoma

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Leukemia, Lymphoid
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Leukemia
Anti-Retroviral Agents
Leukemia, Lymphocytic, Chronic, B-Cell
Therapeutic Uses
Lymphoma
Alkylating Agents

Anti-HIV Agents
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Rituximab
Fludarabine monophosphate
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Aldesleukin
Myeloablative Agonists
Fludarabine
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on July 02, 2009