A Study Of PF-06747143, As Single Agent Or In Combination With Standard Chemotherapy In Adult Patients With Acute Myeloid Leukemia
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: PF-06747143; Cytarabine; Daunorubicin; Azacitidine; Decitabine
Intervention description: PF 06747143 is a humanized IgG1 monoclonal antibody (mAb) that is an antagonist of CXCR4.; 100-200 mg/m2 continuous infusion for 7 days); 60-90 mg/m2 daily for 3 days; 75 mg/m2 sub-cutaneous or intravenous for 7 days); 20 mg/m2 continuous intravenous infusion for 5 days in a 4-week schedule
Intervention MeSH terms: Cytarabine; Azacitidine; Decitabine; Daunorubicin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: relapsed; refractory; acute myeloid leukemia; AML

Summary:

      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.
    

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).