Age ≥18 years.
Body weight >40 kg.
Participants must voluntarily sign a written informed consent and be willing and able to comply with all trial requirements.
For participants with ITP:
For participants with wAIHA:
Diagnosis of relapsed or refractory primary wAIHA.
Hb level <10 g/dL at screening.
Evidence of active hemolysis (e.g., haptoglobin ≤40 mg/dL and total or indirect/unconjugated bilirubin above the upper limit of normal (ULN).
Positive DAT (IgG or IgG + complement C3d pattern or IgM warm autoantibodies [positive dual DAT]).
Received ≥2 lines of prior therapy, including ≥1 first-line therapy (e.g., glucocorticoids, IVIG), and ≥1 second-line therapy (e.g., rituximab, other cytotoxic immunosuppressants, TPO-RAs, Bruton’s tyrosine kinase [BTK] inhibitors, splenectomy), with a history of response to at least one of the prior medications.
For participants with ITP: Prior response is considered ≥2 platelet counts ≥50 K/μL with an increase of ≥20 K/μL from baseline. Relapsed ITP participants are defined as participants who had prior response to ITP therapy that was not sustained, with platelet counts dropping below 30 K/μl after initial response. Refractory participants are defined as participants who had an insufficient response (not meeting the response as defined above) to ≥1 line of standard of care ITP therapy (in addition to a relapse after ≥1 prior line of therapy, as defined above).
For participants with wAIHA: Prior response is considered ≥2 Hb values of >10 g/dL. Relapsed wAIHA participants are defined as participants who had prior response to wAIHA therapy that was not sustained, with Hb counts dropping below 10 g/dL after initial response. Refractory participants are defined as participants who had an insufficient response (not meeting the response as defined above) to ≥1 line of standard of care wAIHA therapy (in addition to a relapse after ≥1 prior line of therapy, as defined above).
Karnofsky performance scale score ≥70%.
Meets organ function criteria to undergo LD chemotherapy and CAR T cell infusion.
Hematologic:
Neutrophil count ≥1.0 × 109/L and ≥2 weeks from the last growth factor support injection (for participants with Duffy null phenotype, neutrophil count ≥0.7 × 109/L).
Absolute lymphocyte count ≥0.3 × 109/L.
Renal:
Liver:
Cardiac:
Hemodynamically stable and no significant electrocardiogram abnormalities that could put the participant at significant risk following CAR T cell therapy, based on investigator judgment in consultation with the sponsor.
Left ventricle ejection fraction ≥45% by echocardiogram or ≥50% by multiple-gated acquisition.
Pulmonary:
Participants on rituximab at the start of the screening period must have been on the medication for ≥3 months prior to screening. Participants on all other immunosuppressants at the start of the screening period must have been on them for ≥1 month prior to screening.
Participants on glucocorticoids must be able to taper to ≤10 mg/day prednisone or equivalent ≥7 days prior to CTX112 infusion.
Participants of childbearing potential (postmenarcheal with an intact uterus and ≥1 ovary, who are <1 year postmenopausal) must agree to use highly effective method(s) of contraception as specified in the protocol from enrollment through ≥12 months after CTX112 infusion.
Participants capable of producing sperm must agree to use acceptable method(s) of contraception as specified in the protocol from enrollment through ≥12 months after CTX112 infusion. 13. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, contraceptive guidelines, and other trial procedures.
Secondary ITP or wAIHA associated with an underlying condition, for example chronic lymphocytic leukemia, viral infection, or drug-associated.
Patients with Evan’s Syndrome, exhibiting co-occurrence of 2 or more immunemediated cytopenias.
Prior treatment with anti-CD19 therapy or any gene therapy or genetically modified cell therapy.
Prior solid organ (e.g., heart, liver, kidney, lung) transplant or hematopoietic cell transplant.
Another active autoimmune disorder besides that under study that could pose increased safety risks and/or confound disease assessments.
Presence of a clinically significant central nervous system pathology or another condition that in the opinion of the investigator may increase CAR T cell–related toxicities.
Known contraindication to cyclophosphamide, fludarabine, or any of the excipients of CTX112 product.
Active or recurrent bacterial, viral, or fungal infection that requires systemic anti-infectives and is considered to pose significant risk to those receiving CAR T cell therapy, based on investigator judgment in consultation with the sponsor.
Active tuberculosis, or latent tuberculosis without completion of appropriate course of intervention. Participants with indeterminant results may be considered after consultation with the sponsor.
Positive for presence of human immunodeficiency virus type 1 or 2, history of hepatitis B virus or active hepatitis C virus (HCV) infection. Participants with prior history of HCV infection who have completed a course of treatment and have documented undetectable viral load (by quantitative polymerase chain reaction or nucleic acid testing) are permitted. Malignancy in the last 5 years (except for non-melanoma skin cancer and other cancers deemed by the investigator and sponsor to be of low likelihood for recurrence).
All patients with (a) bone marrow disorders associated with hypocellularity or impaired hematopoiesis (e.g., aplastic anemia, myelodysplastic syndrome), and/or (b) premalignant myeloid conditions or mutational findings consistent with clinically significant clonal hematopoiesis, as determined by:
bone marrow evaluation within 6 months prior to screening, and
next-generation sequencing (NGS)-based Heme Gene Panel testing as detailed in the protocol
ITP only: Concurrent anticoagulants and platelet aggregation–inhibiting drugs such as aspirin, non-steroidal anti-inflammatory drugs, and thienopyridines within 1 week of CTX112 infusion
Use of therapies as follows:
Treatment with IVIG, plasmapheresis, or a monoclonal antibody (e.g., rituximab) within 30 days prior to CTX112 infusion.
Treatment with cyclophosphamide, vinca alkaloids, or proteosome inhibitors within 30 days prior to CTX112 infusion, or other cytotoxic drugs, immunosuppressants or immunomodulators (e.g., mycophenolate mofetil, azathioprine, methotrexate, calcineurin inhibitors, tyrosine kinase inhibitors) within 7 days prior to CTX112 infusion.
Use of an investigational product within 30 days or 5 half-lives (whichever is longer) prior to CTX112 infusion.
Use of >10 mg/day prednisone or equivalent within 7 days prior to CTX112 infusion.
Evidence of active, clinically significant internal or mucosal bleeding that warrants emergent treatment or therapeutic procedure based on the investigator’s judgment (for example, intracranial hemorrhage, bleeding with ongoing need for transfusion).
Any live or attenuated vaccine during the 28 days prior to enrollment.
Diagnosis of a genetic disorder associated with bone marrow failure or myelodysplastic syndrome, including Fanconi anemia, Kostmann syndrome, Diamond-Blackfan anemia, Shwachman syndrome. Participants with Down syndrome may be enrolled if deemed capable of signing the informed consent form.
History or current diagnosis of catastrophic anti-phospholipid syndrome or anti-phospholipid syndrome that requires ongoing anticoagulation.
Pregnant or lactating. 20. Diagnosis of a significant psychiatric disorder, medical condition, or other assessment that, in the opinion of the investigator, could impede the participant’s ability to participate in the trial. 21. History of alcohol or drug abuse within the year prior to screening.