Clinical Trials /

A Study Of PF-06747143, As Single Agent Or In Combination With Standard Chemotherapy In Adult Patients With Acute Myeloid Leukemia

NCT02954653

Description:

Two part, dose escalation and dose expansion study. Open label, multi center, non randomized, multiple dose, safety, pharmacokinetic and pharmacodynamic study of single agent PF-06747143 in sequential dose levels of adult patients with refractory or relapsed AML in order to establish maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D) or maximally permitted dose (MPD) following by a 3 arm dose expansion with PF-06747143 in combination with standard of care chemotherapy in adult patients with AML.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study Of PF-06747143, As Single Agent Or In Combination With Standard Chemotherapy In Adult Patients With Acute Myeloid Leukemia
  • Official Title: A Phase 1 Dose Escalation Study To Evaluate The Safety, Pharmacokinetics And Pharmacodynamics Of Intravenous Pf-06747143, Administered As Single Agent Or In Combination With Standard Chemotherapy In Adult Patients With Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: B7861002
  • NCT ID: NCT02954653

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
PF-06747143Dose Escalation
CytarabineCohort 1
DaunorubicinCohort 1
AzacitidineCohort 2
DecitabineCohort 2

Purpose

Two part, dose escalation and dose expansion study. Open label, multi center, non randomized, multiple dose, safety, pharmacokinetic and pharmacodynamic study of single agent PF-06747143 in sequential dose levels of adult patients with refractory or relapsed AML in order to establish maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D) or maximally permitted dose (MPD) following by a 3 arm dose expansion with PF-06747143 in combination with standard of care chemotherapy in adult patients with AML.

Detailed Description

      Patients will receive intravenous (IV) PF-06747143 as a weekly infusion (QW) in 28 day cycles
      at escalating doses. The proposed dosing scheme includes 0.3, 1.0, 3.0, 10, 15, and 20 mg/kg.
      Patients will be monitored for dose limiting toxicity (DLT) in the dose escalation in order
      to define the MTD. Two of the three arms in the dose expansion will include PF-06747143 in
      combination with standard of care chemotherapy and will include a safety lead in. The third
      arm, pending clinical data, will be PF-06747143 as a single agent.
    

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalSingle agent PF-06747143 dose escalation
    Cohort 1Active ComparatorPF-06747143 with standard dose cytarabine and daunorubicin.
    • Cytarabine
    • Daunorubicin
    Cohort 2Active ComparatorPF-06747143 in combination with Azacitidine or Decitabine.
    • Azacitidine
    • Decitabine
    Cohort 3ExperimentalPF-06747143 dose expansion as a single agent.

      Eligibility Criteria

              Inclusion Criteria:
      
              Part 1 and Part 2 cohort 3: Patients diagnosed with AML ( bone marrow (BM) or peripheral
              blood (PB) blast counts >/= 20%) and have received prior chemotherapy and/or standard of
              care and have relapsed, refractory or Minimal Residual Disease (defined as patients showing
              residual blast 10-14 days post-induction chemotherapy).
      
              • Patients that are not candidates to receive standard of care and/or refusing the standard
              care of therapies will also be considered.
      
              Part 2 - Cohort 1 and 2: Newly diagnosed, previously untreated de novo or secondary AML
              population (AML with bone marrow or peripheral blast counts 20%):
      
                -  Cohort 1: Fit to receive intensive remission induction chemotherapy.
      
                -  Cohort 2: Unfit to receive or not considered a candidate for intensive remission
                   induction chemotherapy.
      
              Part 1 and 2:
      
                -  Life expectancy at least 12 weeks.
      
                -  Hydroxyurea is allowed on study to control total peripheral white blood cell count but
                   must be ceased 24 hours prior to first dose.
      
                -  Off of prior therapy for 2-4 weeks prior to first dose.
      
                -  ECOG performance status: 0 to 2.
      
                -  Resolved acute effects of any prior therapy.
      
                -  Adequate renal and hepatic function.
      
              Exclusion Criteria:
      
                -  Patients with acute promyelocytic leukemia, AML with known central nervous system
                   (CNS) involvement unless the patient has completed treatment for the CNS disease, has
                   recovered from the acute effects of therapy prior to study entry, and is
                   neurologically stable.
      
                -  Patient is known refractory to platelet or packed red cell transfusions per
                   institutional guidelines.
      
                -  Prior treatment with a compound targeting CXCR4.
      
                -  Chronic systemic corticosteroid treatment.
      
                -  Known or suspected hypersensitivity to recombinant human proteins.
      
                -  Chronic graft versus host disease (GVHD), active GVHD with other than Grade 1 skin
                   involvement, or GVHD requiring systemic immunosuppressive treatment (Part 1 and cohort
                   3).
      
                -  Not recovered from stem cell transplant associated toxicities (Part 1 and cohort 3).
      
                -  Prior treatment with hypomethylating agents or chemotherapy for antecedent
                   myelodysplastic syndrome (MDS) (Part 2, cohort 2)
      
                -  AML associated with favorable risk karyotypes, including inv(16), t(8;21), t(16;16),
                   or t(15;17) (cohort 2)
      
                -  Candidates for allogeneic stem cell transplant (Part 2, cohort 2)
      
                -  Known hypersensitivity to cytarabine or daunorubicin (Part 2, cohort 1) and decitabine
                   or azacitidine or mannitol (Part 2, cohort 2).
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Number of patients with dose limiting toxicity
      Time Frame:Up to 28 days
      Safety Issue:
      Description:

      Secondary Outcome Measures

      Measure:Maximum observed plasma concentrations
      Time Frame:Day 1: 0, 1; 24, 48, 96 hours; Day 8: 0; Day 15: 0, 1 hr; Day 22: 0; Cycle 2: Day 1: 0, 1, 24, 48, 95 hours; Day 8, 15 and 22 and Day 1 of all additional cycles
      Safety Issue:
      Description:
      Measure:Incidence of anti-drug antibodies (ADA)
      Time Frame:Day 1, predose; Day 15, predose; Day 1 of Cycles 2-6 predose then every other cycle Day 1 predose
      Safety Issue:
      Description:
      Measure:Frequency and characterization of adverse events according to CTCAE v4.03
      Time Frame:weekly up to study completion (approximately 12 months)
      Safety Issue:
      Description:Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE v4.03), timing, seriousness, and relationship to study therapy
      Measure:Objective response rate (Part 1)
      Time Frame:up to 16 weeks
      Safety Issue:
      Description:
      Measure:Duration of objective response rate (Part 1)
      Time Frame:up to 16 weeks
      Safety Issue:
      Description:
      Measure:Progression free survival (Part 1)
      Time Frame:up to 16 weeks
      Safety Issue:
      Description:

      Details

      Phase:Phase 1
      Primary Purpose:Interventional
      Overall Status:Terminated
      Lead Sponsor:Pfizer

      Trial Keywords

      • relapsed
      • refractory
      • acute myeloid leukemia
      • AML

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