Clinical Trial 19862

• Overview

  Study Title:

  A Phase 1/1b Safety Study of PRGN-3006 Adoptive Cellular Therapy in Patients with Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndrome

  Summary:

  This is a first-in-human dose escalation/dose expansion study to evaluate the safety and identify the 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). 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.

  Objective:

  Primary objective: To identify and evaluate the safety and MTD of PRGN-3006 T cells in patients with relapsed or refractory AML or higher risk MDS.

• Treatments

  Therapies:

  Cell Therapy; Chemotherapy (NOS)

  Medications:

  PRGN-3006 T Cell (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

• Inclusion Criteria

  • Participants must be diagnosed with either relapsed or refractory CD33+ AML, MRD Positive, AML or higher risk MDS;CD33 positivity must be confirmed by either flow cytometry or immunohistochemistry as per institutional guidelines.
  • Absolute lymphocyte count >0.2 k/ul
  • 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> Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) > 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 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 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, they have not received treatment or prophylaxis for GVHD 6 weeks before administration of CAR T cells, have no active GVHD, have relapsed AML, MRD-Positive AML or MDS as defined above.
  • 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.
  • Patients with peripheral blood blasts >35% are excluded from this study
  • 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 (positive HBsAg test) or hepatitis C (positive HCV RT-PCR 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.

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