Clinical Trials /

Penostatin, Rituximab and Ontak and Allogeneic Natural Killer (NK) Cells for Refractory Lymphoid Malignancies

NCT01181258

Description:

In this study the investigators investigate a cell therapy strategy that could harness allogeneic effectors that can potentially mediate anti-lymphoma effect. The investigators have designed a novel lymphodepleting conditioning regimen followed by infusion of donor-derived natural killer (NK) cells and interleukin-2 (IL-2) for patients with refractory lymphoid malignancies.

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Mature T-Cell and NK-Cell Lymphoma/Leukemia
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Penostatin, <span class="go-doc-concept go-doc-intervention">Rituximab</span> and <span class="go-doc-concept go-doc-intervention">Ontak</span> and Allogeneic Natural Killer (NK) Cells for Refractory Lymphoid Malignancies

Title

  • Brief Title: Penostatin, Rituximab and Ontak and Allogeneic Natural Killer (NK) Cells for Refractory Lymphoid Malignancies
  • Official Title: Lymphodepleting Chemotherapy With Rituximab and Allogeneic Natural Killer Cells for Patients With Refractory Lymphoid Malignancies (MT2009-15)
  • Clinical Trial IDs

    NCT ID: NCT01181258

    ORG ID: 2009LS083

    NCI ID: MT2009-15

    Trial Conditions

    Non-Hodgkin Lymphoma

    Chronic Lymphocytic Leukemia

    Trial Interventions

    Drug Synonyms Arms
    Rituximab Rituxan, MabThera Patients Receiving NK Cell Infusion
    Cyclophosphamide Cytoxan Patients Receiving NK Cell Infusion
    Methylprednisolone Medrol Patients Receiving NK Cell Infusion
    Fludarabine Fludara Patients Receiving NK Cell Infusion

    Trial Purpose

    In this study the investigators investigate a cell therapy strategy that could harness
    allogeneic effectors that can potentially mediate anti-lymphoma effect. The investigators
    have designed a novel lymphodepleting conditioning regimen followed by infusion of
    donor-derived natural killer (NK) cells and interleukin-2 (IL-2) for patients with
    refractory lymphoid malignancies.

    Detailed Description

    This is a single center phase II trial designated to expand donor NK cells and induce
    remissions in patients with refractory non-Hodgkin lymphoma (NHL) and chronic lymphocytic
    leukemia (CLL) using chemotherapy followed by haploidentical NK cells and IL2.

    Primary Objective is to evaluate the objective response rate (PR+CR) at 2 months post
    haploidentical NK cell infusion in patients with refractory Non Hodgkin's Lymphoma (NHL) and
    chronic lymphocytic leukemia (CLL).

    Secondary Objective is to 1) evaluate the safety and tolerability of lymphodepleting
    chemotherapy, rituximab, and methylprednisone as determined by incidence of serious adverse
    events; 2) evaluate in vivo expansion of allogeneic donor NK cells at day 14; 3) determine
    time to progression

    Exploratory Objective is to 1) correlate clinical response with frequencies of peripheral
    blood T reg cells after chemotherapy; 2) correlate clinical response with donor
    KIR-B-content score determined by genotype; 3) monitor phenotypic and functional
    characteristics of natural killer cells and regulatory T cells in vivo; 4) correlate
    clinical response with donor FcR polymorphism.

    - Pre-NK cell infusion chemotherapeutic regimen consist of 1) Rituximab 375mg/m2 IV
    weekly x 4, start day -7; 2) Fludarabine 25 mg/m2 IV day -6 through day -2; 3)
    Cyclophosphamide 60mg/kg IV day -5; 4) Methylprednisolone 1 mg/kg day -2 through day
    +9.

    - NK cell infusion using IL2 activated donor NK cells 1.5 to 8 x 107 cells/kg IV day 0

    - IL2 SC 9 million IU every other day x 6 doses over 2 weeks begin 1 to 24 hours after NK
    cell infusion. If weight < 45 kilograms, give IL-2 at 5 million units/m2 on same
    schedule

    Accrual Goal: Up to 17 patients will be enrolled

    Trial Arms

    Name Type Description Interventions
    Patients Receiving NK Cell Infusion Experimental Non-Myeloablative Conditioning Using Rituximab, Fludarabine, Cyclophosphamide and Methylprednisolone followed by Interleukin 2-activated Allogeneic Natural Killer Cells infusion for Patients with Refractory NHL and CLL Rituximab, Cyclophosphamide, Methylprednisolone, Fludarabine

    Eligibility Criteria

    Inclusion Criteria:

    - Patients of any age with diagnosis of:

    - Relapsed/refractory lymphoma (B cell non-Hodgkin) who have lack of objective
    response to at least two prior chemotherapy regimens

    - Relapsed chronic lymphocytic leukemia with high risk features: lack of objective
    response or relapse within 6 months following nucleoside-analogue based
    chemotherapy regimen or patients with 17p deletion CLL who lacked objective
    response to at least 1 preceding chemotherapy regimen

    - Available related HLA haploidentical NK cell donor by at least Class I serologic
    typing at the A&B locus (age 12-75 years)

    - Karnofsky > 70% for patients 16 years and older and Lansky play score > 50 for
    patients under 16 years of age

    - Measurable disease based on modified Response Evaluation Criteria in Solid Tumors
    (RECIST)

    - Have acceptable organ function as defined within 28 days of enrollment:

    - Hematologic: platelets 80,000 x 10^9/L; hemoglobin 9 g/dL, unsupported by
    transfusions within 7 days; absolute neutrophile count (ANC) 1000 x 10^9/L,
    unsupported by Granulocyte colony-stimulating factor (G-CSF) or
    Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) for 10 days or
    Neulasta for 21 days - the hematologic requirements are waived for patients with
    inadequate counts due to known bone marrow involvement by disease who are
    otherwise eligible

    - Renal: calculated glomerular filtration rate (GFR) > 50 ml/min

    - Hepatic: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5
    x upper limit of normal and total bilirubin 3 mg/dl - hepatic requirements are
    waived for patients with known disease involvement in the liver if otherwise
    eligible

    - Pulmonary function: >40% corrected Carbon Monoxide Diffusing Capacity (DLCO) and
    Forced expiratory volume in one second (FEV1) (oxygen saturation [>92%] can be
    used in child where pulmonary function tests (PFT's) cannot be obtained)

    - Cardiac: no symptoms of uncontrolled cardiac disease, left ventricular ejection
    fraction 40%

    - Able to be off prednisone or other immunosuppressive medications for at least 3 day
    prior to Day 0 (excluding denileukin diftitox pre-medications)

    - Sexually active women of childbearing potential must agree to use adequate
    contraception (diaphragm, birth control pills, injections, intrauterine device [IUD],
    surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration
    of treatment.

    - Voluntary written consent

    Exclusion Criteria:

    - Pregnant or lactating. The agents used in this study may be teratogenic to a fetus
    and there is no information on the excretion of agents into breast milk. All females
    of childbearing potential must have a blood test or urine study within 14 days prior
    to enrollment to rule out pregnancy. Women of childbearing age must use appropriate
    contraceptive method.

    - Active central nervous system (CNS) lymphoma/leukemia - Patients with prior CNS
    involvement are eligible provided that it has been treated and is in remission.

    - 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)

    - Pleural effusion large enough to be detectable on chest x-ray (CXR)

    - Evidence of human immunodeficiency virus (HIV) infection or known HIV positive
    serology

    - Active concurrent malignancy (except skin cancer)

    - Epstein-Barr virus (EBV) post-transplant lymphoproliferative disorder

    - Positive HBsAg. If HBcAb is positive, Hepatitis B DNA by PCR will be evaluated.
    Positive anti HBcAb with an undetectable viral load does not exclude the patient.

    - Any investigational therapy in the past 30 days

    - Patients following allogeneic stem cell transplantation are eligible in the absence
    of graft versus host disease and are off immunosuppression for at least 30 days

    - Known allergy to any of the study agents

    Minimum Eligible Age: N/A

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Objective Response Rate

    Secondary Outcome Measures

    Serious Adverse Events

    Time to Disease Progression

    Patients with Expansion of NK Cells

    Trial Keywords

    related HLA-haploidentical donor