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

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ClinicalTrials.gov Identifier: NCT02152956
Recruitment Status : Recruiting
First Posted : June 2, 2014
Last Update Posted : June 6, 2019
Sponsor:
Collaborator:
Institut de Recherches Internationales Servier
Information provided by (Responsible Party):
MacroGenics

Tracking Information
First Submitted Date  ICMJE May 28, 2014
First Posted Date  ICMJE June 2, 2014
Last Update Posted Date June 6, 2019
Study Start Date  ICMJE May 2014
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 6, 2014)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 28, 2014)
Characterize dose limiting toxicity and to establish a Maximum Tolerated Dose and Schedule (MTDS). [ Time Frame: Cycle 1 of a 28 day cycle. ]
  • Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study Visit. Safety review for the purposes of dose escalation and/or study segment transition will be based on AEs collected during the first cycle of treatment.
  • 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.
Change History Complete list of historical versions of study NCT02152956 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 10, 2019)
  • Occurrence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 7 months ]
  • Occurrence of anti-leukemic activity [ Time Frame: Every 28 days ]
  • Measure the pharmacokinetics (PK) of flotetuzumab [ Time Frame: Cycle 1 through end of treatment (28 day cycles) ]
  • Occurrence of anti-drug antibody [ Time Frame: Cycle 1 through end of treatment (28 day cycles) ]
    ADA
  • Overall survival [ Time Frame: Time from first dose to death from any cause; assessed up to 2 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2014)
  • Describe the safety profile of MGD006 [ Time Frame: Cycle 1 through end of treatment ]
    Evaluation of DLTs, treatment emergent adverse events (TEAEs), and the aggregate safety data
  • Characterize the PK and immunogenicity of MGD006 [ Time Frame: Cycle 1 through end of treatment (28 day cycles) ]
    Serum concentrations of MGD006 will be monitored. Population PK modeling will be performed and an appropriate model will be selected to describe the data.
  • Describe any evidence of anti-leukemic activity [ Time Frame: Every 28 days ]
    Obtain bone marrow aspirate and/or biopsy specimen for local histopathological and immunohistochemical analysis
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study of MGD006 in Relapsed/Refractory Acute Myeloid Leukemia (AML) or Intermediate-2/High Risk MDS
Official Title  ICMJE 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
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE AML
Intervention  ICMJE Drug: Flotetuzumab
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART® molecule.
Other Name: MGD006, S80880
Study Arms  ICMJE Experimental: Flotetuzumab
CD123 x CD3 bispecific DART® antibody
Intervention: Drug: Flotetuzumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 5, 2019)
179
Original Estimated Enrollment  ICMJE
 (submitted: May 28, 2014)
58
Estimated Study Completion Date  ICMJE April 2020
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kathy Tran trank@Macrogenics.com
Listed Location Countries  ICMJE France,   Germany,   Italy,   Netherlands,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02152956
Other Study ID Numbers  ICMJE CP-MGD006-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party MacroGenics
Study Sponsor  ICMJE MacroGenics
Collaborators  ICMJE Institut de Recherches Internationales Servier
Investigators  ICMJE
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
PRS Account MacroGenics
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP