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

• Biological: PF-06747143
  PF 06747143 is a humanized IgG1 monoclonal antibody (mAb) that is an antagonist of CXCR4.
• Drug: Cytarabine
  100-200 mg/m2 continuous infusion for 7 days)
• Drug: Daunorubicin
  60-90 mg/m2 daily for 3 days
• Drug: Azacitidine
  75 mg/m2 sub-cutaneous or intravenous for 7 days)
• Drug: Decitabine
  20 mg/m2 continuous intravenous infusion for 5 days in a 4-week schedule

• Experimental: Dose Escalation
  Single agent PF-06747143 dose escalation
  Intervention: Biological: PF-06747143
• Active Comparator: Cohort 1
  PF-06747143 with standard dose cytarabine and daunorubicin.
  Interventions:

  • Biological: PF-06747143
  • Drug: Cytarabine
  • Drug: Daunorubicin
• Active Comparator: Cohort 2
  PF-06747143 in combination with Azacitidine or Decitabine.
  Interventions:

  • Biological: PF-06747143
  • Drug: Azacitidine
  • Drug: Decitabine
• Experimental: Cohort 3
  PF-06747143 dose expansion as a single agent.
  Intervention: Biological: PF-06747143

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).