Patient case: 26-year-old male with Liposarcoma. Genetic variant: MDM2 Amplification. Other conditions: None.

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

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.

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.

Eligibility: Inclusion Criteria:
  Part 1 and Part 2 cohort 3: (AML patients with bone marrow (BM) and peripheral blood (PB) blast counts 20%): refractory and/or relapsed for which no standard therapies are available:
  -  Patients failed or relapsed from at least 2 previous induction regimens; or
  -  Patients age 65 years old with adverse cytogenetics if they have failed or relapsed from at least one prior induction regimen.
  Part 2 - Cohort 1 and 2:
  1. 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.
  -  Life expectancy at least 12 weeks.
  -  Hydroxyurea is allowed prior to Day 1 to keep peripheral white blood cell (WBC) count less than or equal to 10,000/uL; but must be ceased 24 hours prior to first dose.
  -  Age greater to or equal to 18 years old.
  -  Eastern Cooperative Oncology Group (ECOG) performance status: 0 to 2.
  -  Resolved acute effects of any prior therapy.
  -  Adequate renal and hepatic function.
  -  Negative serum/urine pregnancy test (for females of childbearing potential).
  Exclusion Criteria:
  -  Patients with acute promyelocytic leukemia (APL), 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 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).

Relevance to patient case: not relevant