Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion
Gabriel Mannis

Description

Summary

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.

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

Details

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.

Keywords

AML leukemia myelogenous myeloid refractory Antibodies Flotetuzumab

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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,
  • 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
  • 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

You CAN'T join if...

  • 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.
  • Previous treatment with radiotherapy, cytotoxic chemotherapy, 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 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.

Locations

  • University of California, San Francisco accepting new patients
    San Francisco California 94143 United States
  • City of Hope National Medical Center accepting new patients
    Duarte California 91010 United States

Lead Scientist

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
MacroGenics
ID
NCT02152956
Phase
Phase 1/2
Study Type
Interventional
Last Updated