Patient case: 1-year-old male with acute myeloid leukemia; genetic feature: IDH1

Clinical trial: Safety Study of MGD006 in Relapsed/Refractory Acute Myeloid Leukemia (AML) or Intermediate-2/High Risk MDS

Summary: The primary goal of this Phase 1, dose-escalation study, is to determine the maximum tolerated dose level of MGD006 in patients with AML and MDS whose disease is not expected to benefit from cytotoxic chemotherapy. Studies will also be done to see how the drug acts in the body (pharmacokinetics [PK], pharmacodynamics) and to evaluate potential anti-tumor activity of MGD006.

Detailed description: Open-label, multi-dose, single-arm, multi-center, Phase 1, dose-escalation study to define a maximum tolerated dose and schedule (MTDS), describe preliminarily safety, and to assess PK, immunogenicity, immunomodulatory activity, and potential anti-tumor activity of MGD006 in patients with AML or MDS whose disease is not expected to benefit from cytotoxic chemotherapy.
  This study is designed in three segments: the Single Patient Dose Escalation Segment, followed by the Multi-Patient Dose Escalation Segment and the MTDS Expansion Cohort Segment.
  The Multi-Patient Dose Escalation Segment will employ a classical 3+3 scheme to examine a series of increasing dose escalations in cohorts of patients with either AML or MDS. Patients will be enrolled in one of the two available dosing schedules.
  Once the MTDS is established, the cohort of patients treated at that dose/schedule or a lower dose, will be expanded with the addition of 2 cohorts of 24 patients each (1 cohort for AML and 1 cohort for MDS) to increase the safety experience and more fully evaluate the PK, pharmacodynamics, and activity of MGD006.
  In all segments of the study, patients who benefit from MGD006 treatment, and continue to meet eligibility, may continue treatment in Cycles 2 and beyond.

Eligibility: Inclusion Criteria:
  -  Confirmed diagnosis of primary or secondary AML [any subtype except acute promyelocytic leukemia (APL)] according to World Health Organization (WHO) classification or MDS with an International Prognostic Scoring System (IPSS) risk category of Intermediate 2 or High Risk
  -  Patients with AML must be unlikely to benefit from cytotoxic chemotherapy defined by any one of the following criteria:
  -  leukemia refractory to ≥ 2 induction attempts,
  -  leukemia in 1st relapse with initial CR duration < 6 months,
  -  leukemia in 1st relapse following ≥ 1 unsuccessful salvage attempts,
  -  leukemia in 2nd or higher relapse,
  -  prior treatment failure with at least two cycles of hypomethylating agent.
  -  Patients with MDS must have experienced treatment failure with at least one cycle of hypomethylating therapy or induction therapy and have ≥ 10% bone marrow blasts
  -  Eastern Cooperative Oncology Group (ECOG) performance status ≤2
  -  Life expectancy of at least 4 weeks
  -  Peripheral blast count </= 20,000/mm3 at the time of initiation of infusion on Cycle 1 Day 1
  -  Acceptable laboratory parameters and adequate organ reserve
  -  Adult (≥ 18 years old)
  Exclusion Criteria:
  -  Prior history of allogeneic stem cell transplantation
  -  Prior treatment with an anti-CD123-directed agent
  -  Need for concurrent other cytoreductive chemotherapy
  -  Any prior history of or suspected current autoimmune disorders (with the exception of vitiligo, resolved childhood atopic dermatitis, prior Grave's disease now euthyroid clinically and by laboratory testing)
  -  Second primary malignancy that requires active therapy. Adjuvant hormonal therapy is allowed.
  -  Previous treatment with radiotherapy or immunotherapeutic agents in the 4 weeks prior to study drug administration (Cycle 1 Day 1)
  -  Previous treatment with any other investigational agent in the 4 weeks prior to study drug administration (Cycle 1 Day 1)
  -  Requirement, at the time of study entry, for concurrent steroids > 10 mg/day of oral prednisone or the equivalent, except steroid inhaler, nasal spray or ophthalmic solution
  -  Use of immunosuppressant medications in the 2 weeks prior to study drug administration (Cycle 1 Day 1)
  -  Use of granulocyte colony stimulating or granulocyte-macrophage colony stimulating factor in the 2 weeks prior to study drug administration (Cycle 1 Day 1)
  -  Known central nervous system (CNS) leukemia.

Relevance to patient case: not relevant