Clinical Trials /

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

NCT03826082

Description:

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

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: PRGN-3006 Adoptive Cellular Therapy Relapsed or Refractory CD33-Positive AML or High Risk MDS
  • Official 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

Clinical Trial IDs

  • ORG STUDY ID: MCC-19862
  • NCT ID: NCT03826082

Conditions

  • Myelodysplastic Syndromes
  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
PRGN-3600 T CellsDose Escalation and Expansion of PRGN-3006

Purpose

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

Detailed Description

      This is a single center, nonrandomized, investigator-initiated 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 acute myeloid leukemia (AML) or higher risk myelodysplastic
      syndromes (MDS).

      The study will enroll in two phases: an initial dose escalation phase followed by a dose
      expansion phase.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation and Expansion of PRGN-3006ExperimentalParticipants will be treated in dose escalation phase to identify the safety and maximum tolerated dose (MTD) of PRGN-3006. Doses of genetically modified T cells indicated as CAR-T cell dose/kg recipient weight Dose Level -1: >10^4 but </=3x10^4 cells/kg Dose Level 1: >3x10^4 but </=10^5 cells/kg Dose Level 2: >10^5 but </= 3x10^5 cells/kg Dose Level 3:>3x10^5 but </= 10^6 cells/kg
  • PRGN-3600 T Cells

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants who Experience Dose Limiting Toxicities (DLTs)
Time Frame:Up to Day 42
Safety Issue:
Description:A dose limiting toxicity (DLT) is any of the following and is determined by the investigator to be related to study drug: Aplastic bone marrow, defined by marrow cellularity <5% at Day 28 in the absence of residual disease and confirmed at Day 42. Treatment-emergent CRS of Grade 4 that does not resolve to Grade ≤2 within 72 hours, despite optimal treatment Treatment-emergent CRS of Grade 3 that does not resolve to Grade ≤2 within 2 weeks, despite optimal treatment; Treatment-related Grade 4-5 allergic reactions Treatment-related non-reversible Grade 3 (< 14 days), or any Grade 4-5 autoimmune reactions related to the study cell infusion. Central neurologic toxicity Grade ≥3 lasting more than 14 days Grade 5 Cytokine Release Syndrome (CRS) Tumor Lysis Syndrome ≥ IV (Cairo and Bishop, 2004[2]) that does not resolve within 7 days

Secondary Outcome Measures

Measure:Disease Response in AML Participants
Time Frame:up to 15 years
Safety Issue:
Description:Proportion of AML Patients achieving Partial Response (PR), Complete Response (CR) and/or morphologic leukemia free state (MLFS) as indicated by ELN Response Criteria in AML. Complete Remission with Partial Hematological Recovery (CRh) will also be captured, defined as less than 5% of blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts.
Measure:Disease Response in MDS Patients
Time Frame:Up to 15 years
Safety Issue:
Description:Proportion of MDS Patients achieving Partial Response (PR), Complete Response (CR), or Marrow Complete Response as defined in International Working Group (IWG) 2006 Criteria
Measure:Rate of Absolute Neutrophil Count Recovery
Time Frame:Day 28
Safety Issue:
Description:Rate of Absolute Neutrophil Count Recovery (>0.5 x 10^9/L)
Measure:Absolute Lymphocyte Count (ALC)
Time Frame:Baseline
Safety Issue:
Description:ALC including CD4/CD8 subsets by flow cytometry at baseline (at apheresis) in patients who have successful versus failed PRGN-3006 production.
Measure:Number of PRGN-3006 T Cells
Time Frame:Up to 12 months post treatment
Safety Issue:
Description:Number of PRGRN-3006 T Cells present in patients treated with PRGN-3006

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • MDS
  • AML
  • C33+AML

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