prgn-3006 adoptive cellular therapy for cd33-positive relapsed or refractory aml, mrd positive aml or higher risk mds

Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes

Summary: this is a first-in-human dose escalation/dose expansion study to evaluate the safety and identify the best dose of modified immune cells, prgn-3006 (autologous chimeric antigen receptor (car) t cells), in adult patients with relapsed or refractory acute myeloid leukemia (aml), minimal residual disease (mrd) positive acute myeloid leukemia or higher risk myelodysplastic syndrome (mds). autologous car t cells are modified immune cells that have been engineered in the laboratory to specifically target a protein found on tumor cells and kill them.

this is a multi-center, nonrandomized, phase 1/1b safety and tolerability study. the safety and tolerability of prgn-3006 t cells will be assessed following intravenous administration of escalating doses in patients with relapsed or refractory cd33-positive aml, mrd-positive aml, or higher risk mds. this study has completed the dose escalation phase and is further evaluating prgn-3006 at the identified dose in the dose expansion phase.

Eligibility criteria:
inclusion criteria: * participants must be diagnosed with either relapsed or refractory aml (including extramedullary disease), mrd-positive aml, or higher risk mds. * absolute lymphocyte count ≥ 0.2 k/μl. * karnofsky performance status score ≥60%. * life expectancy ≥ 12 weeks from the time of enrollment. * pretreatment calculated or measured creatinine clearance (absolute value) of ≥ 40 ml/minute or cr \< 2x upper limit of normal (uln). * bilirubin ≤ 2.0 mg/dl or total bilirubin ≤ 3.0 x uln with direct bilirubin within normal range in participants with well documented gilbert's syndrome or hemolysis or who require regular blood transfusions * alanine aminotransferase (ast) and aspartate aminotransferase (alt) \< 3.0 x uln. * ejection fraction measured by echocardiogram (echo) or multi gated acquisition scan (muga) \> 45%. * participant does not require supplemental oxygen or mechanical ventilation and has an oxygen saturation by pulse oximetry of ≥ 92% or higher on room air. * negative serum pregnancy test. note: women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for at least 1 year following study treatment (t cell infusion); should a woman participant or female partner of a male participant become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately. * participant has a matched bone marrow donor and is otherwise able to receive a bone marrow transplant (dose escalation phase only and for participants with mrd-positive aml) * participants who have undergone allo-sct and/or donor lymphocyte infusion (dli) are eligible if they are at least 3 months post sct, prior to apheresis, atleast 30 days post last dli prior to apheresis, have not received treatment or prophylaxis for gvhd 6 weeks before administration of car t cells, have no active gvhd. * all participants must have the ability to understand and willingness to sign a written informed consent. exclusion criteria: * diagnosis of acute promyelocytic leukemia (apl m3): t(15;17)(q22;q12); (promyelocytic leukemia \[pml\]/retinoic acid receptor \[rar\] alpha \[a\]) and variants excluded. * participants with peripheral blood blasts \>35% * known central nervous system (cns) leukemic involvement that is refractory to intrathecal chemotherapy and/or cranio-spinal radiation; participants with a history of cns disease that have been effectively treated to complete remission ( i.e. no blasts in cerebrospinal fluid \[csf\] by cytology and flow cytometry) will be eligible. * prior treatment with investigational cd33 targeting car t therapy for any disease. * prior treatment with licensed or investigational cd33 targeting monoclonal antibody or antibody drug conjugate within 6 months of apheresis. * participants enrolled in another investigational therapy protocol for their disease within 14 days or 5 half-lives of apheresis, whichever is shorter. * ongoing uncontrolled serious infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, poorly controlled pulmonary disease or psychiatric illness/social situations that would limit compliance with study requirements. * human immunodeficiency virus (hiv) seropositivity, or active hepatitis b or c infection based on testing performed within 28 days of enrollment. * participants requiring agents other than hydroxyurea to control blast counts within 14 days of study enrollment. * participants with presence of other active malignancy within 1 year of study entry; participants with adequately resected basal or squamous cell carcinoma of the skin, or adequately resected carcinoma in situ (e.g. cervix) may enroll irrespective of the time of diagnosis. * pregnant and lactating women are excluded from this study * history of allergic reactions attributed to compounds of similar chemical or biological composition to cetuximab (anti-egfr). * active autoimmune disease requiring systemic immunosuppressive therapy (i.e. \>10mg of prednisone daily or equivalent). * participant, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.

Keywords: aml mds