Clinical Trials /

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

NCT02152956

Description:

The primary goal of this Phase 1/2, dose-escalation study, is to determine the maximum tolerated dose level of flotetuzumab in patients with AML 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 flotetuzumab.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety Study of MGD006 in Relapsed/Refractory Acute Myeloid Leukemia (AML) or Intermediate-2/High Risk MDS
  • Official Title: A Phase 1/2, 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 AML or Intermediate-2/High Risk MDS

Clinical Trial IDs

  • ORG STUDY ID: CP-MGD006-01
  • NCT ID: NCT02152956

Conditions

  • AML

Interventions

DrugSynonymsArms
FlotetuzumabMGD006, S80880Flotetuzumab

Purpose

The primary goal of this Phase 1/2, dose-escalation study, is to determine the maximum tolerated dose level of flotetuzumab in patients with AML 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 flotetuzumab.

Detailed Description

      Open-label, multi-dose, single-arm, multi-center, Phase 1/2, 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
      flotetuzumab in patients with AML 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 AML.

      Any Dose Escalation Cohort not exceeding the maximum tolerated dose may be expanded to
      include up to 15 patients for further evaluation of the safety, PK, and preliminary
      anti-tumor activity of flotetuzumab. 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 up to
      120 AML patients.
    

Trial Arms

NameTypeDescriptionInterventions
FlotetuzumabExperimentalCD123 x CD3 bispecific DART® antibody
  • Flotetuzumab

Eligibility Criteria

        Inclusion Criteria:

          -  Confirmed diagnosis of primary or secondary AML [any subtype except acute
             promyelocytic leukemia (APL)] according to World Health Organization (WHO)
             classification

          -  Patients with AML must be unlikely to benefit from recommended standard of care
             defined by any one of the following criteria:

               -  leukemia refractory to ≥ 2 induction attempts (or ≥ 1 for patients > 65 years of
                  age)

               -  leukemia in 1st relapse with initial CR duration < 6 months

          -  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 registration

          -  Acceptable laboratory parameters and adequate organ reserve

        Exclusion Criteria:

          -  Prior treatment with an anti-CD123-directed agent, with the exception of patients with
             relapsed disease after flotetuzumab treatment

          -  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.

          -  Antitumor therapy or investigational agent within 14 days or 5 half-lives of 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 of Cycle 1 Day 1

          -  Use of granulocyte colony stimulating or granulocyte-macrophage colony stimulating
             factor in the 2 weeks of Cycle 1 Day 1

          -  Known central nervous system (CNS) leukemia.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Occurrence of dose limiting toxicity
Time Frame:Cycle 1 of a 28 day cycle.
Safety Issue:
Description:• Maximum Tolerated Dose/Schedule: the MTDS will be defined as the highest dose/schedule administered during any Cohort in the study at which the incidence of DLT is < 33% during the first cycle of MGD006 treatment.

Secondary Outcome Measures

Measure:Occurrence of adverse events (AEs) and serious adverse events (SAEs)
Time Frame:Up to 7 months
Safety Issue:
Description:
Measure:Occurrence of anti-leukemic activity
Time Frame:Every 28 days
Safety Issue:
Description:
Measure:Measure the pharmacokinetics (PK) of flotetuzumab
Time Frame:Cycle 1 through end of treatment (28 day cycles)
Safety Issue:
Description:
Measure:Occurrence of anti-drug antibody
Time Frame:Cycle 1 through end of treatment (28 day cycles)
Safety Issue:
Description:ADA
Measure:Overall survival
Time Frame:Time from first dose to death from any cause; assessed up to 2 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:MacroGenics

Trial Keywords

  • AML
  • leukemia
  • myelogenous
  • myeloid
  • refractory

Last Updated

October 30, 2019