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 : September 13, 2017
Institut de Recherches Internationales Servier
Information provided by (Responsible Party):

Brief Summary:
The primary goal of this Phase 1, dose-escalation study, is to determine the maximum tolerated dose level of MGD006 in patients with AML and MDS 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 MGD006.

Condition or disease Intervention/treatment Phase
AML MDS Drug: MGD006 Phase 1

Detailed Description:

Open-label, multi-dose, single-arm, multi-center, Phase 1, 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 MGD006 in patients with AML or MDS 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 either AML or MDS. Patients will be enrolled in one of the two available dosing schedules.

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 2 cohorts of 24 patients each (1 cohort for AML and 1 cohort for MDS) to increase the safety experience and more fully evaluate the PK, pharmacodynamics, and activity of MGD006.

In all segments of the study, patients who benefit from MGD006 treatment, and continue to meet eligibility, may continue treatment in Cycles 2 and beyond.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 124 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, 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 : October 2017
Estimated Study Completion Date : April 2018

Arm Intervention/treatment
Experimental: MGD006
MGD006, a CD123 x CD3 Dual Affinity Re-Targeting (DART®) bi-specific antibody
Drug: MGD006
MGD006 is a CD123 x CD3 bi-specific antibody-based molecular construct referred to as a Dual Affinity Re-Targeting (DART®) molecule. MGD006 will be administered as a single agent.

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: Cycle 1 through end of treatment ]
  2. Occurrence of anti-drug antibody (ADA) [ Time Frame: Cycle 1 through end of treatment (28 day cycles) ]
  3. Occurrence of anti-leukemic activity [ Time Frame: Every 28 days ]
  4. Measure the pharmacokinetics (PK) of MGD006 [ Time Frame: Cycle 1 through end of treatment (28 day cycles) ]

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 or MDS with an International Prognostic Scoring System (IPSS) risk category of Intermediate 2 or High Risk
  • Patients with AML must be unlikely to benefit from cytotoxic chemotherapy 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.
  • Patients with MDS must have experienced treatment failure with at least one cycle of hypomethylating therapy or induction therapy and have ≥ 10% bone marrow blasts
  • 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
  • Adult (≥ 18 years old)

Exclusion Criteria:

  • Prior history of allogeneic stem cell transplantation
  • Prior treatment with an anti-CD123-directed agent
  • 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 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 prior to study drug administration (Cycle 1 Day 1)
  • Use of granulocyte colony stimulating or granulocyte-macrophage colony stimulating factor in the 2 weeks prior to study drug administration (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

Contact: Kathy Tran

United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Joseph Nimm    404-778-4994   
Principal Investigator: H. Jean Khoury, MD, FACP         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Ayan Gasanli    314-747-2449   
Principal Investigator: Geoffrey Uy, MD         
Sub-Investigator: John DiPersio, MD         
United States, North Carolina
University of North Carolina Lineberger Comprehensive Cancer Center Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Jack Zhang    984-974-8251   
Principal Investigator: Mathew C. Foster, MD         
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Rachel Stowe, BSN, RN    919-681-4769   
Principal Investigator: David Rizzieri, MD         
United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: Neysa Dagostino, RN, OCN    503-215-2608   
Principal Investigator: John Godwin, MD         
Institut Paoli-Calmettes Recruiting
Marseille, France, 13002
Contact: Caroline Veuillen   
Principal Investigator: Norbert Vey, MD         
Medizinische Klinik und II, Universitätsklinikum Würzburg Recruiting
Würzbur, Germany, 97080
Contact: Johana Reif   
Principal Investigator: Max Topp, MD         
Policlinico Sant'Orsola Malpighi Recruiting
Bologna, Italy, 40138
Contact: Federica Frabetti   
Principal Investigator: Giovanni Martinelli, MD         
University Vita-Salute San Raffaele Recruiting
Milano, Italy, 20132
Contact: Stefania Trinca   
Principal Investigator: Fabio Ciceri, MD         
University Medical Center Groningen Recruiting
Groningen, Netherlands, 9713
Contact: Erna Helmantel   
Principal Investigator: Gerwin Huls, MD         
Erasmus University Medical Center Recruiting
Rotterdam, Netherlands, 3075
Contact: Sarah Longergan   
Principal Investigator: Bob Lowenberg, MD         
Sponsors and Collaborators
Institut de Recherches Internationales Servier
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

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: September 13, 2017
Last Verified: September 2017

Keywords provided by MacroGenics:

Additional relevant MeSH terms:
Antibodies, Bispecific
Immunologic Factors
Physiological Effects of Drugs