Phase 1 Study of Allo-RevCAR01-T-CD123 in Patients With Selected CD123 Positive Hematologic Malignancies

Exclusion Criteria28

• Acute promyelocytic leukemia (t15;17).
• AML with only extramedullary manifestations (e.g., chloroma, primary myeloid sarcoma)
• Acute manifestationof AML in the central nervous system.
• Bone marrow failure syndromes
• Cardiac disease: heart failure (New York Heart Association III or IV); unstable coronary artery disease, myocardial infarction, or serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy within the last 6 months prior to study entry.
• Active pulmonary disease with clinically relevant hypoxia
• Parkinson's disease or epilepsy with clinical symptoms in the previous 12 months .
• Stroke, seizure, or intracranial hemorrhage in the past 12 months.
• History or presence of disseminated intravascular coagulation (DIC), deep vein thrombosis or thromboembolism within 3 months prior to start of treatment.
• Active infectious disease considered by investigator to be incompatible with protocol or being contraindications for lymphodepletion therapy
• Presence of hemorrhagic cystitis
• Other toxicity from prior anticancer treatment has not resolved to Grade ≤1 or baseline.
• Allogeneic stem cell transplantation within last 2 months or GvHD requiring systemic immunosuppressive therapy.
• Vaccination with live viruses \< 2 weeks prior to lymphodepletion therapy.
• Major surgery within 28 days prior to start of R-TM123 infusion.
• Prior malignancy in the past 3 years or any malignancy requiring ongoing active therapy other than adjuvant endocrine therapy. Participants with resected or ablated tumors, such as basal cell carcinoma of skin, carcinoma-in-situ of the cervix, or other tumors considered cured may be considered for the study with Sponsor approval.
• Treatment with any investigational drug substance or experimental therapy within 4 weeks or 5 half-lives (whichever is shorter) of the substance prior to lymphodepletion.
• Treatment with anti-leukemic therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to lymphodepletion.
• Prior treatment with gene modified cell products.
• Use of checkpoint inhibitors within 5 half-lives of the specific drug.
• Autoimmune diseases requiring systemic steroids or other systemic immunosuppressants.
• Pregnant or breastfeeding women.
• Psychologic disorders with treatment modifications required within the last 3 months, drug and/or significant active alcohol abuse as per investigator's medical judgement. Depression or anxiety due to presence of the underlying malignancy may be exempted with Sponsor approval.
• History of human immunodeficiency virus (HIV) or human T-lymphotropic virus (HTLV) or active/chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV).
• Presence of autoantibodies against lupus La protein (La)/ Sjögren syndrome type B antigen (SS-B) or presence or history of autoimmune diseases associated with such antibodies
• Known hypersensitivity to cellular component (Allo-RevCAR01-T) and/or TM (R-TM123) excipients or to compounds of the lymphodepletion therapy, tocilizumab, or corticosteroids.
• Evidence that the participant is not likely or able to follow the study protocol (e.g., lacking compliance) in the judgment of the investigator.
• Participant unable to understand the informed consent and possible consequences of the participation in the clinical trial in the judgement of the investigator.