PRGN-3006 Adoptive Cellular Therapy Relapsed or Refractory CD33-Positive AML or High Risk MDS

• Status: Not yet recruiting
• Trial end date: 2035-04-01
• Target enrollment: 56
• Participant gender: All

Summary

Thi study is to determine the safety and best dose of PRGN-3006 T Cells.

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

Details

• Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Criteria

Inclusion Criteria:

• Participants must be diagnosed with either relapsed or refractory CD33+ AML or higher risk MDS

• Absolute lymphocyte count ≥ 0.2 k/μL.

• Karnofsky performance status score ≥60%.

• Life expectancy 12 weeks or more 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.

• 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

• Participants with extramedullary disease as their sole site of relapsed AML.

• 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 will be eligible.

• Prior treatment with investigational CAR-T therapy for any disease.

• Participants enrolled in another investigational therapy protocol for AML 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 may enroll irrespective of the time of diagnosis.

• Pregnant and breastfeeding women.

• 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).

• Participants who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.