Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCSD UCSF
Dates
study started
estimated completion
Principal Investigator
Matthew Wieduwilt, MD (ucsd)Peter Sayre, MD (ucsf)
Photo of Matthew Wieduwilt
Matthew Wieduwilt

Description

Summary

The primary goal of this Phase 1/2, dose-escalation study, is to determine the maximum tolerated dose level of flotetuzumab (MGD006) 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 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:
  • AML refractory to ≥ 2 (or ≥ 1 for patients > 65 years of age) induction attempts, including but not limited to the following:
  • AML refractory to ≥ 1 intensive induction attempt(s), per institution, including high- and standard-dose cytarabine ± an anthracyclines/anthracenedione ± an anti-metabolite with or without growth factor or targeted therapy,

ii. for adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy, AML refractory to ≥ 2 lower intensity induction attempts including Bcl-2 or Hedgehog inhibitors with azacitidine/decitabine/LDAC or available targeted therapies such as FLT3/IDH1/IDH2/anti-CD33 antibodies;

  1. AML in 1st relapse with initial CR duration < 6 months,
  2. a maximum of up to 2 prior salvage attempts is allowed.
  3. Eastern Cooperative Oncology Group (ECOG) performance status ≤2
  4. Life expectancy of at least 4 weeks
  5. Peripheral blast count </= 20,000/mm3 at the time of registration
  6. Acceptable laboratory parameters and adequate organ reserve

You CAN'T join if...

  • History of allogeneic stem cell transplantation.
  • 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.

Locations

  • UCSD Moores Cancer Center accepting new patients
    La Jolla California 92093 United States
  • University of California, San Francisco accepting new patients
    San Francisco California 94143 United States

Lead Scientists at UC Cancer

  • Matthew Wieduwilt, MD (ucsd)
    Associate Clinical Professor, Medicine. Authored (or co-authored) 20 research publications. Research interests: Acute lymphoblastic leukemia (ALL) · Acute myeloid leukemia (AML) · Bone marrow transplant · Clinical trial design and conduct.
  • Peter Sayre, MD (ucsf)
    Professor, Medicine. Authored (or co-authored) 33 research publications. Research interests: Immune tolerance · hematologic malignancies · food allergy · transplantation tolerance · cellular therapies.

Details

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