Clinical Trials /

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

NCT03927261

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:

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: NCT03927261

Conditions

  • Myelodysplastic Syndromes
  • Acute Myeloid Leukemia

Interventions

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

Purpose

This 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 acute myeloid leukemia (AML) or higher risk myelodysplastic syndromes (MDS).

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

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation and Dose Expansion of PRGN-3006ExperimentalParticipants will be treated in dose escalation phase to identify the safety and maximum tolerated dose (MTD) of PRGN-3006.
  • PRGN-3006 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 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.

          -  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 ( 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 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 (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.
      
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 Progression 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) by ELN Response Criteria in AML. CRh (complete PRGN-3006 T cells in patients with AML/MDS remission with partial hematological recovery) will also be captured, defined as <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 a response (CR, PR or Marrow CR) 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 PRGN-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

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