Donor Natural Killer Cell Infusion, Rituximab, Aldesleukin, and Chemotherapy in Treating Patients With Relapsed Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Leukemia; Lymphoma
Intervention: aldesleukin (Biological); lymphokine-activated killer cells (Biological); rituximab (Biological); cyclophosphamide (Drug); fludarabine phosphate (Drug); laboratory biomarker analysis (Other); pharmacogenomic studies (Other); pharmacological study (Other)
Phase: Phase 1/Phase 2
Sponsored by: Masonic Cancer Center, University of Minnesota
Official(s) and/or principal investigator(s):
Veronika Bachanova, MD, Principal Investigator, Affiliation: Masonic Cancer Center, University of Minnesota
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.
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 design: Treatment, Open Label
Primary outcome: Safety of expanding donor-derived natural killer (NK) cells to > 100 cells/μL by day 14 after fludarabine, cyclophosphamide, and rituximab
Correlation of interleukin-15 production at day 0 with NK cells expansion
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
Time to progression and overall survival
Quantitative and qualitative toxicities
Incidence of donor products that do not meet release criteria and the
NK cell numbers infused
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)
Correlation of pharmacodynamics and pharmacogenomics with NK cell expansion and disease response
- 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 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 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
CLL also undergo bone marow aspiration periodically for correlative laboratory studies.
After completion of study treatment, patients are followed periodically for up to 1 year.
Minimum age: 18 Years.
Maximum age: N/A.
- 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 purine analogs) in stage Rai III or IV or
- 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
- 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)
- 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
- FEV_1 > 50% corrected
- LVEF > 40%
- 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 NOTE: *The hematologic requirements are waived for patients with
inadequate counts due to known bone marrow involvement by lymphoma who are otherwise
PRIOR CONCURRENT THERAPY:
- At least 3 days since prior prednisone or other immunosuppressive medications
- At least 30 days since prior experimental therapy
Locations and Contacts
Masonic Cancer Center at University of Minnesota, Minneapolis, Minnesota 55455, United States; Recruiting
Clinical Trials Office - Masonic Cancer Center at University o, Phone: 612-624-2620
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: January 2008
Last updated: October 7, 2009