CD70.CAR NK Cells for the Treatment of Primary Refractory or Early Relapsed Diffuse Large B-Cell Lymphoma and Hodgkin Lymphoma

Inclusion Criteria

• 18-75 years of age
• Diagnosis of classic Hodgkin lymphoma (cHL) or DLBCL that is either: * Primary refractory, defined as not having achieved a complete response (CR) with frontline therapy or having relapsed within 3 months * Early relapsed (≤ 12 months) after achieving a CR to frontline therapy
• Tumor biopsy positive for CD70 >= 10% by immunohistochemistry or flow cytometry
• Measurable disease, defined by one or more histologically confirmed hypermetabolic lesion on PET/CT scan
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2 (Karnofsky ≥ 60%)
• White blood cell (WBC) > 2K
• Hemoglobin (HGB) > 8 g/dL
• Platelets > 50K
• Creatinine clearance ≥ 30 ml/min
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN)
• Bilirubin ≤ 2 x ULN
• Alkaline phosphatase (ALP) ≤ 2 x ULN
• Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide corrected (DLCOc) ≥ 50%
• Left ventricular ejection fraction (LVEF) ≥ 40%, without active arrythmias
• If female of child-bearing potential, she must not be pregnant or breastfeeding and is required to have a negative urine or serum pregnancy test prior to enrollment
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
• Patients with a prior or concurrent malignancy whose natural history or treatment does not interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
• The effects of CAR-NK cells on the developing human fetus are unknown. For this reason and because fludarabine and cyclophosphamide, as well as other therapeutic agents used in this trial are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation * This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following: ** Postmenopausal (no menses in greater than or equal to 12 consecutive months) ** History of hysterectomy or bilateral salpingo-oophorectomy ** Ovarian failure (follicle stimulating hormone and estradiol in menopausal range, who have received whole pelvic radiation therapy) ** History of bilateral tubal ligation or another surgical sterilization procedure * Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device (IUD), tubal ligation or hysterectomy, subject/partner post vasectomy, implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately * Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of CAR NK cell administration
• Ability to understand and the willingness to sign a written informed consent document
• Agree to sign consent to the long-term follow-up protocol PA17-0843 to fulfill the institutional responsibilities to various regulatory agencies

Exclusion Criteria

• Lymphoma in CR with no measurable sites of disease
• Major surgery < 4 weeks prior to first dose of study drug
• Any other severe or uncontrolled disease or condition which might increase the risk associated with study participation
• Any other malignancy known to be active, with the exception of treated cervical intra-epithelial neoplasia and non-melanoma skin cancer
• Grade >= 3 non-hematologic toxicity from prior therapy that has not improved to grade =< 2
• Active hepatitis B, either active carrier (hepatitis B virus surface antigen [HBsAg] +) or viremic (HBV deoxyribonucleic acid [DNA] >= 10,000 copies/mL, or >= 2,000 IU/mL), or hepatitis C (detectable viral load by HCV ribonucleic acid [RNA] polymerase chain reaction [PCR])
• Active infection requiring parenteral antibiotics
• HIV infection
• Treatment within prior 2 weeks with any anti-cancer agent, investigational or approved
• Active central nervous system (CNS) involvement (untreated parenchymal brain metastasis or positive cytology of cerebrospinal fluid)
• Life expectancy =< 6 months
• Active and uncontrolled neurological disorder
• Patients receiving systemic steroid therapy at time of enrollment (physiological replacement doses are allowed) or have received antithymocyte globulin or lymphocyte immune globulin within 14 days of enrollment or alemtuzumab within 28 days of enrollment
• Patients receiving immunosuppressive therapy