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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02152956
Recruitment Status : Recruiting
First Posted : June 2, 2014
Last Update Posted : June 6, 2019
Institut de Recherches Internationales Servier
Information provided by (Responsible Party):

Brief 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.

Condition or disease Intervention/treatment Phase
AML Drug: Flotetuzumab Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 179 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : May 2014
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : April 2020

Arm Intervention/treatment
Experimental: Flotetuzumab
CD123 x CD3 bispecific DART® antibody
Drug: Flotetuzumab
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART® molecule.
Other Name: MGD006, S80880

Primary Outcome Measures :
  1. Occurrence of dose limiting toxicity [ Time Frame: Cycle 1 of a 28 day cycle. ]
    • 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 :
  1. Occurrence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 7 months ]
  2. Occurrence of anti-leukemic activity [ Time Frame: Every 28 days ]
  3. Measure the pharmacokinetics (PK) of flotetuzumab [ Time Frame: Cycle 1 through end of treatment (28 day cycles) ]
  4. Occurrence of anti-drug antibody [ Time Frame: Cycle 1 through end of treatment (28 day cycles) ]

  5. Overall survival [ Time Frame: Time from first dose to death from any cause; assessed up to 2 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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,
    • 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

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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02152956

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Contact: Kathy Tran

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Sponsors and Collaborators
Institut de Recherches Internationales Servier
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Principal Investigator: John DiPersio, MD, PhD Washington University School of Medicine
Study Director: Jan Davidson-Moncada, MD, PhD MacroGenics
Principal Investigator: Norbert Vey, MD Institute Paoli-Calmettes

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Responsible Party: MacroGenics Identifier: NCT02152956     History of Changes
Other Study ID Numbers: CP-MGD006-01
First Posted: June 2, 2014    Key Record Dates
Last Update Posted: June 6, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by MacroGenics:

Additional relevant MeSH terms:
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Immunologic Factors
Physiological Effects of Drugs