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



Juni 2014

Letztes Update:


Indikation (Clinical Trials):
Leukemia, Myeloid, Acute


Erwachsene (18+)



Institut de Recherches Internationales Servier


John DiPersio, MD, PhD
Principal Investigator
Washington University School of Medicine
Jan Davidson-Moncada, MD, PhD
Study Director
Norbert Vey, MD
Principal Investigator
Institute Paoli-Calmettes


(3 von 35)

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
01307 Dresden
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Max Langner
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Gynäkologisches Tumorzentrum am Universitätsklinikum Leipzig
4103 Leipzig
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Karolin Hubert
Phone: + 49 341 97-20363
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Universitätsmedizin der Johannes Gutenberg-Universität Mainz
55131 Mainz
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Britta Vornwald
Phone: +49 6131 17 5160
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III. Med. Klinik-Klinikum rechts der Isar-Technische Universität München
81675 Munich
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Christine Ernst
Phone: +49 89 41405145
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UCSD Moores Cancer Center
92093 La Jolla
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Marisa Wiegand
Phone: 858-822-6396

Emma Bishop
Phone: 858-822-1960
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University of North Carolina Lineberger Comprehensive Cancer Center
27599 Chapel Hill
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Allison McKinney
Phone: 919-966-4432
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Cleveland Clinic
44195 Cleveland
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Kaylee Root
Phone: 216-444-3576

Eric Wiedenfeld
Phone: 216-445-0003
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The University of Texas MD Anderson Cancer Center
77030 Houston
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Melissa J. McFarland
Phone: 713-745-1216
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Institut Universitaire du Cancer de Toulouse-Oncopole
31059 Toulouse
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Elodi Judic
Phone: +33 5 31 15 58 74
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Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)
74014 Meldola
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Frederica Frabetti
Phone: 390543739292
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Unità Operativa di Ematologia Ospedale Santa Maria delle Croci
48123 Ravenna
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Francesca Fabbri
Phone: 0039 054 428 5103
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The Christie NHS Foundation Trust
M20 4BX Manchester
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Ryan Roberts
Phone: +44 161 446 3000
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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.


Inclusion Criteria:

- Confirmed diagnosis of primary or secondary AML [any subtype except acute

promyelocytic leukemia (APL)] according to World Health Organization (WHO)


- 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


- 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, nasal spray or ophthalmic


- 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


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 COVID-19/SARS-CoV-2 infection. While SARS-CoV-2 testing is not mandatory for

study entry, testing should follow local clinical practice guidelines/standards.

Participants with a positive test result for SARS-CoV-2 infection, known asymptomatic

infection, or suspected infection are excluded.


Primary outcome:

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:

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, progression, 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

Geprüfte Regime

  • Flotetuzumab (MGD006):
    Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART® molecule.


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