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Flotetuzumab in Primary Induction Failure (PIF) or Early Relapse (ER) Acute Myeloid Leukemia (AML)

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 : May 25, 2021
Information provided by (Responsible Party):

Brief 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).

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 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 330 participants
Allocation: N/A
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 DART® Bi-Specific Antibody Based Molecule, in Patients With Relapsed or Refractory AML or Intermediate-2/High Risk Myelodysplastic Syndrome (MDS)
Actual Study Start Date : June 9, 2014
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2022

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

Primary Outcome Measures :
  1. Efficacy based on CR/CRh rate [ Time Frame: 14 months ]
    Proportion of patients achieving a best response of CR (morphologic CR [mCR], cytogenetic CR [CRc], molecular CR [CRm], or CRh per Interworking Group AML response criteria.

Secondary Outcome Measures :
  1. Overall complete response rate [ Time Frame: 14 months ]
    Rate of CR + CRh + CRi (CR with incomplete blood cell recovery [CR with incomplete neutrophil or platelet recovery]) + MLFS (morphologic leukemia-free state)

  2. CR rate [ Time Frame: 14 months ]
    Proportion of patients achieving a best response of CR (morphologic CR [mCR], cytogenetic CR [CRc], or molecular CR [CRm] per Interworking Group AML response criteria.

  3. CRh rate [ Time Frame: 14 months ]
    Proportion of patients achieving a best response of CRh per Interworking Group AML response criteria.

  4. Duration of response [ Time Frame: Up to 2 years ]
    Time of initial documentation of response to the time of disease relapse or death due to any cause, whichever occurs first.

  5. Transfusion independence rate [ Time Frame: 56 days ]
    The rate of conversion from transfusion dependence to transfusion independence will be calculated. The rate of patients who are transfusion independent at baseline and remain independent during any 56-day post-baseline period will also be calculated.

  6. Overall survival [ Time Frame: Up to 2 years ]
    Time from first dose to death from any cause

  7. HSCT rate [ Time Frame: 8 months ]
    Rate of successful hematopoietic stem cell transplantation (HSCT) through flotetuzumab treatment but before subsequent therapy.

  8. Incidence rate of hospitalization [ Time Frame: 8 months ]
    Incidence rate of hospitalization will be calculated

  9. Duration of hospitalization [ Time Frame: 8 months ]
    Duration of hospitalization will be characterized

  10. Event-free survival [ Time Frame: Up to 2 years ]
    Time from the first dose of study drug until date of evidence of progression, relapse, or death from any cause, whichever occurs first.

  11. Time to response [ Time Frame: 14 months ]
    Time from first dose of study drug to first CR, CRh, CR with incomplete blood cell recovery (CRi), CR with incomplete neutrophil recovery (CRn), CR with incomplete platelet recover (CRp), or morphologic leukemia-free state (MLFS)

  12. Mortality rate [ Time Frame: Up to 180 days ]
    rate of death from any cause within 30, 60, 90, or 180 days of first dose of study drug

  13. 6-month survival rate [ Time Frame: 6 months ]
    Probability of survival at 6 months from first dose of study drug

  14. One-year survival rate [ Time Frame: 1 year ]
    Probability of survival at 1 year from first dose of study drug

  15. Infusion related reaction (IRR)/cytokine release syndrome (CRS) management [ Time Frame: During study drug administration (up to 8 months) ]
    Determine safety and efficacy of tocilizumab in the treatment of IRR/CRS as measured by incidence of IRR/CRS

Other Outcome Measures:
  1. Occurrence of dose limiting toxicity [ Time Frame: Cycle 1 of a 28 day cycle. ]
    Maximum Tolerated Dose/Schedule: the MTDS is 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.

  2. Occurrence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 9 months ]
    Cycle 1 through end of treatment

  3. Serum concentration of flotetuzumab [ Time Frame: Cycles 1 and 2 (28-day cycles) and 28 days after the last dose ]
    Measure the pharmacokinetics (PK) of flotetuzumab

  4. ADA [ Time Frame: Day 1 of Cycle 1 and Day 1 of Cycle 2 (28-day cycles) ]
    Occurrence of anti-drug antibody

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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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 meet one of the following criteria, a or b:

    a. 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:

1. ≥ 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

Exclusion Criteria:

  • 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, otic preparations, 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:

    i. 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 SARS-CoV-2 infection. While SARS-CoV-2 testing is not mandatory for study entry, testing for ongoing infection should follow local clinical practice guidelines/standards. Participants with a positive test result for ongoing SARS-CoV-2 infection, known asymptomatic infection, or suspected infection are excluded unless or until asymptomatic and with subsequent negative SARS-CoV-2 laboratory test.

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
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Principal Investigator: John DiPersio, MD, PhD Washington University School of Medicine
Study Director: Stephen L. Eck, MD, PhD MacroGenics
Principal Investigator: Norbert Vey, MD Institute Paoli-Calmettes
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: MacroGenics Identifier: NCT02152956    
Other Study ID Numbers: CP-MGD006-01
First Posted: June 2, 2014    Key Record Dates
Last Update Posted: May 25, 2021
Last Verified: May 2021

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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: