Summary

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

Description

Summary

The primary objective of this study now is to assess the anti-neoplastic activity of flotetuzumab in patients with PIF/ER AML, as determined by the proportion of patients who achieve complete remission (CR) or complete remission with partial hematologic recovery (CRh).

Official Title

A Phase 1/2, First in Human, Dose Escalation Study of MGD006, a CD123 x CD3 DART® Bi-Specific Antibody Based Molecule, in Patients With Relapsed or Refractory AML or Intermediate-2/High Risk Myelodysplastic Syndrome (MDS)

Details

Open-label, multi-dose, single-arm, multi-center, Phase 1/2 study conducted in three segments: the Single Patient Dose Escalation Segment (complete), followed by the Multi-Patient Dose Escalation Segment (complete) and the Maximum Tolerated Dose and Schedule (MTDS) Expansion Cohort Segment (ongoing). Having characterized safety and determined the maximum tolerated dose and schedule, the primary objective of this study now is to assess the anti-neoplastic activity of flotetuzumab in patients with PIF/ER AML, as determined by the proportion of patients who achieve CR or CRh. Starting with Cycle 2, patients who are benefiting from flotetuzumab may receive up to a maximum of 8 cycles of treatment.

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 meet one of the following criteria, a or b:
  • Primary Induction Failure (PIF) AML, defined as disease refractory to one of the following, i or ii: i. An intensive induction attempt, per institution. Induction attempts include high-dose and/or standard-dose cytarabine

± an anthracyclines/anthracenedione ± an anti-metabolite, with or without growth factor or targeted therapy containing regimens.

Examples include but are not limited to:

  1. One cycle of high dose cytarabine (HiDAC) containing regimen
  2. One cycle of liposomal cytarabine and daunorubicin
  3. Two cycles of standard dose cytarabine containing regimen ii. For adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy; PIF is defined as AML refractory to one of the following less intensive regimens, 1 or 2:
  4. ≥ 2 but ≤ 4 cycles of Bcl-2 inhibitors in combination with azacitidine, decitabine, or low dose cytarabine 2. ≥ 2 but ≤ 4 cycles of gemtuzumab ozogamicin monotherapy b. Early relapse (ER) AML, defined as AML in first relapse with initial CR1 duration < 6 months 3.

Limit of 3 prior lines of therapy: up to 2 induction (induction, re-induction) or 1 induction plus/minus 1 consolidation attempt, followed by a maximum of 1 salvage/re-induction attempt.

  • 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 first dose
  • 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
  • Need for concurrent other cytoreductive chemotherapy
  • Any active untreated autoimmune disorders (with the exception of vitiligo, resolved childhood atopic dermatitis, prior Grave's disease now euthyroid clinically and with stable supplementation)
  • 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
  • Active uncontrolled infection (including, but not limited to viral, bacterial, fungal, or mycobacterial infection),
  • Known human immunodeficiency virus infection, unless all of the following criteria are met:
  • CD4+ count ≥ 350 cells/μL, ii. undetectable viral load, and iii. receiving highly active antiretroviral therapy.
  • Known, active, history of or current acute or chronic hepatitis B or C virus (HBV) infection (as evidenced by detectable HBV surface antigen and HBV DNA ≥ 500 IU/mL),
  • History of hepatitis C virus (HCV) infection, unless the infection has been treated and cured,
  • Active COVID-19/SARS-CoV-2 infection. While SARS-CoV-2 testing is not mandatory for study entry, testing should follow local clinical practice guidelines/standards. Participants with a positive test result for SARS-CoV-2 infection, known asymptomatic infection, or suspected infection are excluded.

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 Health

  • Matthew Wieduwilt, MD (ucsd)
    Associate Clinical Professor, Medicine. Authored (or co-authored) 23 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) 34 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