Chimeric Antigen Receptor T Cell Therapy Redirected to CD4 (CD4CAR)as a Second Line Treatment for Chronic Myelomonocytic Leukemia, CMML.

Inclusion Criteria: 1. ≥ 18 years old at the time of informed consent 2. Ability to provide written informed consent and HIPAA authorization 3. Diagnosis of CMML that is CD4+ and is recurrent or refractory to first line standard of care treatment. 4. Creatinine clearance of ≥ 60 ml/min (or otherwise non clinically significant, per study investigator) 5. ALT/AST \< 3 x ULN 6. Bilirubin \< 2 x ULN 7. No supplemental oxygen at rest Note: Pulmonary Function Test (PFT) only required per treating physician discretion. 8. Adequate cardiac function with EF of ≥50%. This will not have to be repeated if within 45 days of initial assessment 9. Adequate venous access for apheresis and no other contraindications for leukapheresis Exclusion Criteria: 1. CD4 negative CMML 2. Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential (see definition below) must have a negative serum or urine pregnancy test prior to initiation of conditioning chemotherapy, per research sites' clinical policy 3. Uncontrolled active infection necessitating systemic therapy 4. Active hepatitis B or hepatitis C infection. Active hepatitis C is defined as the hepatitis C antibody is positive while quantitative HCV 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 5. Concurrent use of systemic glucocorticoids in greater than replacement doses 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, pseudo rheumatism, emotional disturbances, etc) precipitated by the temporary stoppage unless tapering can occur safely without compromising the underlying disease, the withdrawal tolerance and can happen in a timeframe appropriate to enroll in this trial without safety concerns Subjects who receive daily corticosteroids in replacement doses can be included in the study. The replacement doses are defined as following: 1. Hydrocortisone 25mg/day or less 2. Prednisone 10mg/day or less 3. Dexamethasone 4mg or less - Note: Recent or current use of inhaled glucocorticoids is not exclusionary, as this route pertains extremely minimal systemic penetration 6. Any uncontrolled active medical disorder that would preclude participation as outlined in the opinion of the treating investigator and/or Principal Investigator 7. HIV infection 8. Subjects who have received or will receive live vaccines within 30 days before the first experimental cell treatment. Inactivated seasonal flu vaccination is allowed 9. Subjects with active autoimmune diseases who need systematic treatments (such as disease modifying agents, corticosteroids and immunosuppressive drugs) during the last year 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 10. Subjects with a history of mental disorders or drug abuse that may influence treatment compliance 11. Active malignancy not related to CMML 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 CMML patients who transformed into AML and who were treated back into CMML status are eligible. CMML patients who transformed into AML and appropriate AML treatment was unsuccessful in reverting their disease back to CMML status will be treated as AML patients and are not eligible for the CMML study. 12. Treatment with any investigational cell/gene therapy within the past 6 months 13. Treatment with any investigational anticancer agent within the last 14 days of study entry or 5 half-lives (whichever is shorter) Eligibility for Conditioning Chemotherapy: 1. Specific organ function criteria for cardiac, renal, and liver function must be similar to initial inclusion values 2. Review of co-morbidities to confirm no major changes in health status (examples of major changes include heart attack, stroke, and any major trauma) 3. Planned infusion dose was successfully manufactured and met release criteria 4. Negative pregnancy testing (if applicable) Eligibility for cd4CAR Infusion Inclusion 1. Afebrile and not receiving antipyretics, and no evidence of active infection. If fever is attributed to underlying disease, it will not disqualify. 2. Specific organ function criteria for cardiac, renal, and liver function must be similar to initial inclusion values. The following test does not need repeated: EF if within 6 weeks of initial assessment. 3. If previous history of corticosteroid chemotherapy, subject must be off all but adrenal replacement doses 3 days before the CD4CAR infusion Exclusion Note: A subject may still receive the CD4CAR infusion up to 10 days post conditioning chemotherapy as long as they do not meet any of the following at time of infusion: 1. Requirement for supplemental oxygen to keep saturation greater than 95% or presence of radiographic abnormalities on a clinically indicated chest x-ray that are progressive. 2. New cardiac arrhythmia not controlled with medical management. 3. Hypotension requiring pressor support. 4. Positive blood cultures for bacteria, fungus, or virus within 48-hours of T cell infusion. Contraception and Reproductive Potential Guidelines Female subjects of reproductive potential (women who have reached menarche or women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or have not undergone a sterilization procedure \[hysterectomy or bilateral oophorectomy\]) must have a negative serum or urine pregnancy test prior to conditioning chemotherapy. Due to the high-risk level of this study, while enrolled, all subjects must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization). Additionally, if participating in sexual activity that could lead to pregnancy, the study subject must agree to use reliable and double barrier methods of contraception from time of consent through at least 90 days after CD4CAR infusion. Acceptable birth control includes a combination of two of the following methods: * Condoms (male or female) with or without a spermicidal agent. * Diaphragm or cervical cap with spermicide * Intrauterine device (IUD) * Hormonal-based contraception Subjects who are not of reproductive potential (women who have been post-menopausal for at least 24 consecutive months or have undergone hysterectomy, salpingotomy, and/or bilateral oophorectomy or men who have documented azoospermia) are eligible without requiring the use of contraception. Acceptable documentation of sterilization, azoospermia, and menopause is specified next: Written or oral documentation communicated by clinician or clinician's staff of one of the following: * Physician report/letter * Operative report or other source documentation in the subject record (a laboratory report of azoospermia is required to document successful vasectomy) * Discharge summary * Laboratory report of azoospermia * Follicle stimulating hormone measurement elevated into the menopausal range