CD4-Directed Chimeric Antigen Receptor T-cells for the Treatment of Patients with Relapsed or Refractory CD4+ Hematologic Cancers

Inclusion Criteria

• Patients must voluntarily sign and date informed consent forms that state his or her willingness to comply with all study procedures and availability for the duration of the study
• Age 12 years old or older
• Subjects with any documented CD4+ T cell hematologic malignancies. Male and female subjects with CD4+ T-cell hematologic malignancies with either relapsed or refractory disease (including those patients who have undergone a prior transplant [if allogeneic, subjects are eligible if there are no remaining donor cells] and patients with an inadequate response after 4-6 cycles of standard chemotherapy) are eligible. Response criteria for each disease subset will be evaluated based on Standard of Care Guidelines
• Creatinine clearance of > 60 ml/min (or otherwise non clinically-significant, per study investigator)
• Alanine transaminase (ALT) and aspartate aminotransferase (AST) < 3 x upper limit of normal (ULN)
• Bilirubin < 2 x ULN
• Pulmonary function test (PFT) with a diffusing capacity of the lungs for carbon monoxide (DLCO) of >= 60%
• Adequate echocardiogram with ejection fraction (EF) of >= 50%
• Adequate venous access for apheresis and no other contraindications for leukapheresis
• CONDITIONING CHEMOTHERAPY: Specific organ function criteria for cardiac, renal, and liver function must be similar to initial inclusion values
• CONDITIONING CHEMOTHERAPY: Review of co-morbidities to confirm no major changes in health status (examples of major changes include heart attack, stroke, and any major trauma)
• CONDITIONING CHEMOTHERAPY: Planned infusion dose was successfully manufactured and met release criteria
• CD4CAR INFUSION: Afebrile and not receiving antipyretics, and no evidence of active infection
• CD4CAR INFUSION: Specific organ function criteria for cardiac, renal, and liver function must be similar to initial inclusion values. The following tests do not need repeated: an echocardiogram if within 6 weeks of initial assessment, and the PFT if completed within 6 months from day 0
• CD4CAR INFUSION: Negative pregnancy testing (if applicable)
• CD4CAR INFUSION: If previous history of corticosteroid chemotherapy, subject must be off all but adrenal replacement doses 3 days before the CD4CAR infusion

Exclusion Criteria

• Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum or urine pregnancy test prior to initiation of conditioning chemotherapy, per research sites’ clinical policy
• Uncontrolled active infection necessitating systemic therapy
• Active hepatitis B or hepatitis C infection. Active hepatitis C is defined as the hepatitis C antibody is positive while quantitative hepatitis C virus (HCV) ribonucleic acid (RNA) results exceed the lower detection limit. Note the following subjects will be eligible: * Subjects with a history of hepatitis B but have received antiviral therapy and have non-detectable viral DNA for 6 months prior to enrollment are eligible * Subjects seropositive for HBS antibodies due to hepatitis B virus vaccine with no signs or active infection (Negative HBs Ag, HBc and HBe Ags) are eligible * Subjects who had hepatitis C but have received antiviral therapy and show no detectable hepatitis C virus (HCV) viral RNA for 6 months are eligible * If hepatitis C antibody test is positive, then patients must be tested for the presence of antigen by reverse transcription-polymerase chain reaction (RT-PCR) and be hepatitis C virus ribonucleic acid (HCV RNA) negative
• Concurrent use of systemic glucocorticoids in greater than replacement doses (unless as a part of a standard of care salvage therapy or conditioning protocol), or steroid dependency defined in rheumatological and pulmonary diseases as uninterrupted corticosteroid intake for more than a year at a dosage of 0.3 mg/kg/day or greater, and where the underlying disease worsens on temporary stoppage of steroid therapy, with symptoms of steroids withdrawal (eg, lethargy, headache, weakness, pseudorheumatism, emotional disturbances, etc) precipitated by the temporary stoppage. Subjects who receive daily corticosteroids in replacement doses can be included in the study. The replacement doses are defined as following: * Hydrocortisone 25mg/day or less * Prednisone 10mg/day or less * Dexamethasone 4mg or less Note: Recent or current use of inhaled glucocorticoids is not exclusionary, as this route pertains extremely minimal systemic penetration
• Any previous treatment with any gene therapy products
• Any uncontrolled active medical disorder that would preclude participation as outlined in the opinion of the treating investigator and/or study chair
• Human immunodeficiency virus (HIV) infection
• Patients declining to consent for treatment
• Subjects who have received or will receive live vaccines within 30 days before the first experimental cell treatment. Inactivated seasonal flu vaccination is allowed
• Subjects with active autoimmune diseases who need systematic treatments (such as disease modifying agents, corticosteroids and immunosuppressive drugs) in the last 2 years. Note: Replacement therapy (thyroxine, insulin or physiological corticosteroid replacement therapy (up to10 mg of oral daily prednisone or equivalent in hydrocortisone and dexamethasone) to treat adrenal dysfunction or pituitary dysfunction) is not considered as systematic therapy. Subjects who need inhalation corticosteroid therapy can be included in this trial. Subjects with vitiligo or in long-term remission of pediatric asthma or allergic diseases can be included in this trial
• Subjects with a history of mental disorders or drug abuse that may influence treatment compliance
• Active malignancy not related to a T-cell malignancy that has required therapy in the last 3 years or is not in complete remission. Exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or prostate cancer that does not require therapy. Other similar malignant conditions may be discussed with and permitted by the Principal Investigator
• Participation in another clinical study with an investigational product within the past 18 months