PRGN-3006 Adoptive Cellular Therapy for Relapsed or Refractory AML or High Risk MDS

• Status: Recruiting
• Trial end date: 2025-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a first-in-human dose escalation/dose expansion study to evaluate safety and identify best dose (or recommended Phase 2 dose) of modified immune cells, PRGN-3006 (autologous chimeric antigen receptor (CAR) T cells), in adult patients with relapsed or recurred acute myeloid leukemia (AML), high-risk myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML). 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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute; PGEN Therapeutics, Inc., a subsidiary of Precigen, Inc.
• Collaborator: Precigen, Inc

Criteria

Inclusion Criteria:

• Participants must be diagnosed with either relapsed or refractory AML (including extramedullary disease) or higher risk MDS/CMML.

• 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).

• Serum bilirubin ≤ 2.0 mg/dL or total bilirubin ≤ 3.0 x IULN 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 IULN.

• 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 part only)

• Participants who have undergone allo-SCT are eligible if they are at least 3 months post SCT, have relapsed AML/MDS as defined above, are not on treatment or prophylaxis for GVHD for at least 6 weeks before administration of CAR T cells, and 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.

• 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 CAR T therapy for any disease.

• Participants enrolled in another investigational therapy protocol for their disease within 14 days or 5 half-lives of enrollment, 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.