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

This study is currently recruiting participants.
See Contacts and Locations
Verified April 2017 by MacroGenics
Sponsor:
Collaborator:
Institut de Recherches Internationales Servier
Information provided by (Responsible Party):
MacroGenics
ClinicalTrials.gov Identifier:
NCT02152956
First received: May 28, 2014
Last updated: April 10, 2017
Last verified: April 2017
  Purpose
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 Intervention Phase
AML MDS Drug: MGD006 Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
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

Resource links provided by NLM:


Further study details as provided by MacroGenics:

Primary Outcome Measures:
  • 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:
  • Occurrence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Cycle 1 through end of treatment ]
  • Occurrence of anti-drug antibody (ADA) [ Time Frame: Cycle 1 through end of treatment (28 day cycles) ]
  • Occurrence of anti-leukemic activity [ Time Frame: Every 28 days ]
  • Measure the pharmacokinetics (PK) of MGD006 [ Time Frame: Cycle 1 through end of treatment (28 day cycles) ]

Estimated Enrollment: 124
Study Start Date: May 2014
Estimated Study Completion Date: April 2018
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

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

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02152956

Contacts
Contact: Kathy Tran trank@Macrogenics.com

Locations
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Joseph Nimm    404-778-4994    joseph.nimm@emory.edu   
Principal Investigator: H. Jean Khoury, MD, FACP         
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Ayan Gasanli    314-747-2449    agasanli@wustl.edu   
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    jack_zhang@med.unc.edu   
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    rachel.stowe@duke.edu   
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    neysa.dagostino@providence.org   
Principal Investigator: John Godwin, MD         
France
Institut Paoli-Calmettes Recruiting
Marseille, France, 13002
Contact: Caroline Veuillen       veuillenc@ipc.unicancer.fr   
Principal Investigator: Norbert Vey, MD         
Germany
Medizinische Klinik und II, Universitätsklinikum Würzburg Recruiting
Würzbur, Germany, 97080
Contact: Johana Reif       Reif_J@ukw.de   
Principal Investigator: Max Topp, MD         
Italy
Policlinico Sant'Orsola Malpighi Recruiting
Bologna, Italy, 40138
Contact: Federica Frabetti       federica.frabetti2@studio.unibo.it   
Principal Investigator: Giovanni Martinelli, MD         
University Vita-Salute San Raffaele Recruiting
Milano, Italy, 20132
Contact: Stefania Trinca       trinca.stefania@hsr.it   
Principal Investigator: Fabio Ciceri, MD         
Netherlands
University Medical Center Groningen Not yet recruiting
Groningen, Netherlands, 9713
Contact: Erna Helmantel       e.helmantel@umcg.nl   
Principal Investigator: Gerwin Huls, MD         
Erasmus University Medical Center Not yet recruiting
Rotterdam, Netherlands, 3075
Contact: Sarah Longergan       s.lonergan@erasmusmc.nl   
Principal Investigator: Bob Lowenberg, MD         
Sponsors and Collaborators
MacroGenics
Institut de Recherches Internationales Servier
Investigators
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
  More Information

Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT02152956     History of Changes
Other Study ID Numbers: CP-MGD006-01
Study First Received: May 28, 2014
Last Updated: April 10, 2017

Keywords provided by MacroGenics:
AML
leukemia
myelogenous
myeloid
refractory
MDS
Myelodysplastic

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

ClinicalTrials.gov processed this record on June 28, 2017