Clinical Trial 19229

Cancer Type: Malignant Hematology
Interventions:MGD006

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Kendra Sweet

Overview

Study Title

A Phase 1, First-in-Human, Dose Escalation Study of MGD006, a CD123 x CD3 Dual Affinity Re-Targeting (DART) Bi-Specific Antibody-Based Molecule, in Patients with Relapsed or Refractory Acute Myeloid Leukemia or Intermediate- 2/High Risk Myelodysplastic Syndrome

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.

Objective

The Primary Objective of this study is: To characterize the dose-limiting toxicities (DLTs), and determine the maximum tolerated dose and schedule (MTDS) for the administration of MGD006 when given by continuous intravenous (IV) infusion for seven days in the first week followed by continuous IV infusion either for 4 days on / 3 days off or 7 days continuously during the first of sequential 4-week cycles in patients with relapsed or refractory AML or intermediate-2/high risk MDS. The Secondary Objectives of this study are: - To describe, in preliminary fashion, the safety profile of MGD006 when administered by continuous IV infusion in 4-week cycles over a broad dose range. - To characterize the pharmacokinetics (PK) and immunogenicity of MGD006 when given by continuous IV infusion over a broad dose range. - To describe any evidence of anti-neoplastic activity in AML and MDS. EXPORATORY OBJECTIVES: For patients with MDS, to evaluate the effect of MGD006 on the need for transfusion and/or growth factor support. - To evaluate the utility of CD123 expression on blast cells in AML and MDS as a biomarker. - To evaluate cytokine production by immune effector cells over time. - To evaluate changes in leukemic and normal cells in PBMCs over time. - To evaluate changes in T lymphocyte populations and activation markers over time. - To evaluate changes in leukemic cells, leukemic stem cells and normal progenitor.cells over time in bone marrow. - To evaluate molecular markers of minimal residual disease (MRD). - To examine changes in T lymphocyte repertoire. - To gain experience with the use of certain anti-cytokine agents in the prevention.and/or treatment of life-threatening cytokine release syndrome.

Inclusion Criteria

  • Confirmed diagnosis of primary or secondary acute myeloid leukemia (AML) [any subtype except acute promyelocytic leukemia (APL)] according to World Health Organization (WHO) classification or myelodysplastic syndrome (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 complete response (CR) duration less than 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 less than or equal to 2
  • Life expectancy of at least 4 weeks > Peripheral blast count less than or equal to 20,000/mm^3 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