Chimeric Antigen Receptor T Cell Redirected to Target CD4 Positive Relapsed Refractory Acute Myeloid Leukemia (AML ) as a Bridge to Allogeneic Stem Cell Transplant

Exclusion Criteria

• •1. CD4 negative AML
• •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 hb, or hepatitis C, HC, 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 subjects 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 (e.g., 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 AML 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.
• •12. Treatment with any investigational cell/gene therapy within the past 6 months
• •13. Treatment with any investigational anticancer agent within the past 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 does was successfully manufactured and met release criteria.
• •4. Negative pregnancy testing (if applicable).
• •Eligibility for CD4CAR infusion:
• •1. Afebrile and not receiving antipyretics, and no evidence of active infection per PI discretion. 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 tests does not need repeated: EF if within 6 weeks of screening assessment.
• •Note: Subjects may require a repeat PFT prior to CD4CAR infusion as determined by the treating physician in the following possible cases:
• •* Subject develops a respiratory infection that results in significant changes in lung imaging from baseline
• •* Subject's oxygenation from daily activities is compromised at baseline; or there is a significant change in oxygenation or lung imaging from baseline
• •3. If previous history of corticosteroid chemotherapy, subject must be off all but adrenal replacement doses 3 days before the CD4CAR infusion.
• •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.