Lymphodepleting Chemotherapy With Rituximab and Allogeneic Natural Killer Cells for Patients With Refractory Lymphoid Malignancies (MT2009-15)
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