Phase 1 Study of Allo-RevCAR01-T-CD123 in Patients With Selected CD123 Positive Hematologic Malignancies (1b Dose Expansion)

Ki vehet részt

• Male or female participants, age ≥18 years. 2. HLA type of participant must match at HLA B and C loci 3. Participants with CD123+ AML with morphologically relapsed or refractory disease (>5% BM blasts). CD123 positivity is defined as ≥20% of leukemic cells expressing CD123 at any point in the course of disease
• Up to third relapse for whom all standard or life-extending therapies have failed and for whom no potentially curative therapies are available or who are intolerant to such therapies
• Without prior myeloproliferative neoplasm (MPN) or MDS/MPN (including leukemic transformation of MPN, "blast phase", and "accelerated phase" MPN), and without hyperproliferative disease requiring cytoreductive treatment within 4 weeks from the screening or with WBC above ULN at screening
• Exceptions to minimum CD123 expression are not allowed. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. Life expectancy of at least 3 months in the judgment of the investigator. 6. Adequate renal and hepatic laboratory assessments. 7. Adequate cardiac function. 8. Long-term central venous access existing (e.g., tunneled CV catheter or port-system) or willing to have such a device inserted to ensure continuous R-TM123 administration
• Able to give written informed consent. 10. Weight is greater than the minimum weight required for a specific batch to ensure that the dose administered does not exceed 10\^5 TCR+ cells/kg of patient weight
• Negative pregnancy; routinely using a highly effective method of birth control

Ki nem vehet részt

• 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
• Parkinson's disease or epilepsy with clinical symptoms in the previous 6 months
• History or presence of disseminated intravascular coagulation (DIC), deep vein thrombosis or thromboembolism within 3 months prior to start of treatment
• 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
• 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
• Bone marrow failure syndromes
• Active pulmonary disease with clinically relevant hypoxia (SpO₂ <92% on room air or daily need for supplemental oxygen)
• Stroke, seizure, or intracranial hemorrhage in the past 12 months
• Active infectious disease considered by investigator to be incompatible with protocol or being contraindications for lymphodepletion therapy
• Prior malignancy in the past 3 years or any malignancy requiring ongoing active therapy other than adjuvant endocrine therapy. Participants with malignancy within the last 3 years, but 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
• Autoimmune diseases requiring systemic steroids or other systemic immunosuppressants
• 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)
• Known 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. (Results from recent sampling are not required for eligibility unless MH or other facts indicate La/SS-B would likely be positive.)
• Known hypersensitivity to cellular component (Allo-RevCAR01-T) and/or TM (R-TM123) excipients or to compounds of the lymphodepletion therapy, tocilizumab, or corticosteroids
• Acute promyelocytic leukemia (t15;17) or myeloproliferative neoplasm (MPN) per WHO 2022 diagnostic criteria
• AML with only extramedullary manifestations (e.g., chloroma, primary myeloid sarcoma)
• Active manifestation of AML in the central nervous system
• Presence of hemorrhagic cystitis
• Pregnant or breastfeeding women
• 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 judgment of the investigator