AMLPhase 1/2VOYAGENCT02152956
Flotetuzumab in Primary Induction Failure (PIF) or Early Relapse (ER) Acute Myeloid Leukemia (AML)
A Phase 1/2 study testing Flotetuzumab 3 ng/kg/day, 4 days on and 3 days off, Flotetuzumab 10 ng/kg/day, 4 days on and 3 days off and Flotetuzumab 30 ng/kg/day, 4 days on and 3 days off in people with AML, run by MacroGenics at 43 sites in 8 countries.
Trial summary
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 (closed). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AML
- What is being tested?
- Flotetuzumab 3 ng/kg/day, 4 days on and 3 days off, Flotetuzumab 10 ng/kg/day, 4 days on and 3 days off and Flotetuzumab 30 ng/kg/day, 4 days on and 3 days off
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 244 participants
- Where
- 43 sitesin 8 countries
- Study dates
- 9 Jun 2014to 5 Jul 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- Primary Induction Failure (PIF) AML, defined as disease refractory to either, 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 cycle of high dose cytarabine (HiDAC) containing regimen, 1 cycle of liposomal cytarabine and daunorubicin, 2 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: i ≥ 2 but ≤ 4 cycles of Bcl-2 inhibitors in combination with azacitidine, decitabine, or low dose cytarabine, or ii ≥ 2 but ≤ 4 cycles of gemtuzumab ozogamicin monotherapy
- Early relapse (ER) AML, defined as AML in first relapse with initial CR1 duration < 6 months
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- Limit of 3 prior lines of therapy (excluding focal radiation therapy for palliative purposes): 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
Who cannot join
- 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.
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- 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 prior to Cycle 1 Day 1
- Use of granulocyte colony stimulating or granulocyte-macrophage colony stimulating factor in the 2 weeks prior to 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: CD4+ count ≥ 350 cells/μL, undetectable viral load, and 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.
Trial locations and contacts
43 sites in 8 countries.
43 sites in 8 countries
United States20 sites
University of Michigan
Ann Arbor, Michigan, 48109
Emory University
Atlanta, Georgia, 30322
University of Maryland
Baltimore, Maryland, 21201
University of North Carolina Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Cleveland Clinic
Cleveland, Ohio, 44195
City of Hope National Medical Center
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27710
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
UCSD Moores Cancer Center
La Jolla, California, 92093
Loyola University Chicago - Cardinal Bernadin Cancer Center
Maywood, Illinois, 60153
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
Providence Portland Medical Center
Portland, Oregon, 97213
UCSF - Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115
University of California, San Francisco
San Francisco, California, 94143
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
Washington University School of Medicine
St Louis, Missouri, 63110
Stony Brook Medicine
Stony Brook, New York, 11794
Moffitt Cancer Center
Tampa, Florida, 33612
Georgetown University - Lombardi Cancer Center
Washington D.C., District of Columbia, 20057
Germany7 sites
Charité - Universitätsmedizin Berlin
Berlin, 13353
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
Dresden, 01307
Universitätsklinik Hamburg-Eppendorf
Hamburg, 20246
Universitätsklinikum Leipzig
Leipzig, 04103
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, 55131
III. Med. Klinik-Klinikum rechts der Isar-Technische Universität München
Munich, 81675
Medizinische Klinik und II, Universitätsklinikum Würzburg
Würzbur, 97080
France4 sites
Institut Paoli-Calmettes
Marseille, 13002
Centre Hospitalier Universitaire de Nantes
Nantes, 44093
Institut Universitaire du Cancer de Toulouse-Oncopole
Toulouse, 31059
CHRU de Tours - Hôpital Bretonneau
Tours, 37044
Italy4 sites
Policlinico Sant'Orsola Malpighi
Bologna, 40138
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)
Meldola, 74014
University Vita-Salute San Raffaele
Milan, 20132
Unità Operativa di Ematologia Ospedale Santa Maria delle Croci
Ravenna, 48123
Israel2 sites
Rambam Health Care Campus
Haifa
Shaare Zedek Medical Center
Jerusalem
Netherlands2 sites
University Medical Center Groningen
Groningen, 9713
Erasmus University Medical Center
Rotterdam, 3075
Spain2 sites
Universitat Autonomaa de Barcelona (UAB) - Hospital de la Santa Creu i de Sant Pau
Barcelona
Hospital Universitario 12 de Octubre
Madrid
United Kingdom2 sites
King's Health Partners
London
The Christie NHS Foundation Trust
Manchester, M20 4BX
About this study
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)
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 (closed). 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.
Patients will receive daily increasing doses of flotetuzumab for the first week of Cycle 1 (Lead-In Dosing) followed by 3 weeks of continuous intravenous infusion at a the assigned dose. Subsequent cycles are each 4 weeks of continuous infusion at the assigned dose. Dosing may continue for up to 8 cycles. Follow up visits may continue for 6 months after treatment is discontinued.
- Conditions
- AML
- Being tested
- Flotetuzumab 3 ng/kg/day, 4 days on and 3 days off, Flotetuzumab 10 ng/kg/day, 4 days on and 3 days off, Flotetuzumab 30 ng/kg/day, 4 days on and 3 days off, Flotetuzumab 100 ng/kg/day, 4 days on and 3 days off, Flotetuzumab 300 ng/kg/day, 4 days on 3 days off, after one-step lead-in dose
- Keywords
- AML, leukemia, myelogenous, myeloid, refractory
- Medical subject headings
- Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Flotetuzumab 3 ng/kg/day, 4 days on and 3 days offBiological
Also called MGD006
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART® molecule.
Flotetuzumab 10 ng/kg/day, 4 days on and 3 days offBiological
Also called MGD006
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
Flotetuzumab 30 ng/kg/day, 4 days on and 3 days offBiological
Also called MGD006
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
Flotetuzumab 100 ng/kg/day, 4 days on and 3 days offBiological
Also called MGD006
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
Flotetuzumab 300 ng/kg/day, 4 days on 3 days off, after one-step lead-in doseBiological
Also called MGD006
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
Flotetuzumab 500 ng/kg/day, 4 days on 3 days off, after one-step lead-in doseBiological
Also called MGD006
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART® molecule.
Flotetuzumab 500 ng/kg/day, continuous infusion, after multi-step lead-in doseBiological
Also called MGD006
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
Flotetuzumab 700 ng/kg/day, 4 days on 3 days off, after multi-step lead-in doseBiological
Also called MGD006
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
Flotetuzumab 700 ng/kg/day, continuous infusion, after multi-step lead-in doseBiological
Also called MGD006
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
RuxolitinibDrug
Also called Jakafi
Oral inhibitor of JAK kinase
Flotetuzumab 300 ng/kg/day, continuous infusion, after multi-step lead-in doseBiological
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 0-a | Experimental | Not described Receives: Biological: Flotetuzumab 3 ng/kg/day, 4 days on and 3 days off |
| Cohort 0-b | Experimental | Not described Receives: Biological: Flotetuzumab 10 ng/kg/day, 4 days on and 3 days off |
| Cohort 0-c | Experimental | Not described Receives: Biological: Flotetuzumab 30 ng/kg/day, 4 days on and 3 days off |
| Cohort 0-d | Experimental | Not described Receives: Biological: Flotetuzumab 100 ng/kg/day, 4 days on and 3 days off |
| Cohort 1 | Experimental | Not described Receives: Biological: Flotetuzumab 300 ng/kg/day, 4 days on 3 days off, after one-step lead-in dose |
| Cohort 2 | Experimental | Not described Receives: Biological: Flotetuzumab 500 ng/kg/day, 4 days on 3 days off, after one-step lead-in dose |
| Cohort 2a | Experimental | Not described Receives: Biological: Flotetuzumab 500 ng/kg/day, continuous infusion, after multi-step lead-in dose |
| Cohort 3 | Experimental | Not described Receives: Biological: Flotetuzumab 700 ng/kg/day, 4 days on 3 days off, after multi-step lead-in dose |
| Cohort 6 | Experimental | Not described Receives: Biological: Flotetuzumab 300 ng/kg/day, continuous infusion, after multi-step lead-in dose |
| Cohort 7 | Experimental | Not described Receives: Biological: Flotetuzumab 500 ng/kg/day, continuous infusion, after multi-step lead-in dose |
| Cohort 8 | Experimental | Not described Receives: Biological: Flotetuzumab 700 ng/kg/day, continuous infusion, after multi-step lead-in dose |
| MTD Expansion | Experimental | Not described Receives: Biological: Flotetuzumab 500 ng/kg/day, continuous infusion, after multi-step lead-in dose |
| MTD expansion with Ruxolitinib | Experimental | Not described Receives: Biological: Flotetuzumab 500 ng/kg/day, continuous infusion, after multi-step lead-in dose; Drug: Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy Based on CR or CRh Rate
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.
CR is defined as mCR, CRc, CRm or CRh. mCR is defined as: normal. neutrophil and platelet counts, less than 5% blast cells in a bone marrow (BM) smear and. no extramedullary disease.
CRc is defined as: CR with no evidence of cytogenetic abnormalities in the bone marrow.
CRm is defined as: CR with no evidence of molecular abnormalities in the bone marrow.
CRh is defined as: CR with partial hematologic recovery.
Measured: up to 14 months
Secondary outcomes (22)
Overall Complete Response Rate
Rate of CR + CRh + CRi (CR with incomplete blood cell recovery [CR with incomplete neutrophil {CRn}or platelet recovery {CRp}]) + MLFS (morphologic leukemia-free state)
Measured: up to 14 months
CR Rate
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.
CR is defined as mCR, CRc, CRm or CRh. mCR is defined as: normal. neutrophil and platelet counts, less than 5% blast cells in a bone marrow (BM) smear and. no extramedullary disease.
CRc is defined as: CR with no evidence of cytogenetic abnormalities in the bone marrow.
CRm is defined as: CR with no evidence of molecular abnormalities in the bone marrow.
CRh is defined as: CR with partial hematologic recovery.
Measured: up to 14 months
CRh Rate
Proportion of patients achieving a best response of CRh per Interworking Group AML response criteria.
CRh is defined as: CR with partial hematologic recovery.
Measured: up to 14 months
Overall Response Rate
Proportion of patients achieving a best response of CR, CRh, CRi, MLFS or partial response per Interworking Group AML response criteria.
CR is defined as mCR, CRc, CRm or CRh. mCR is defined as: normal. neutrophil and platelet counts, less than 5% blast cells in a bone marrow (BM) smear and. no extramedullary disease.
CRc is defined as: CR with no evidence of cytogenetic abnormalities in the bone marrow.
CRm is defined as: CR with no evidence of molecular abnormalities in the bone marrow.
CRh is defined as: CR with partial hematologic recovery.
Measured: up to 14 months
HSCT Rate
Rate of successful hematopoietic stem cell transplantation (HSCT) after the start flotetuzumab treatment and before subsequent therapy.
Measured: up to 8 months
Occurrence of Dose Limiting Toxicity
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.
Measured: Cycle 1 of a 28 day cycle.
Occurrence of Adverse Events (AEs)
Cycle 1 through end of treatment
Measured: up to 9 months
Occurrence of Serious Adverse Events (SAEs)
Measured: up to 9 months
Participants With Anti-drug Antibodies
Occurrence of anti-drug antibody
Measured: Study Day 1, then every 28 days through 28-days after the last dose (up to 8 months)
Number of Patients With Infusion Related Reaction (IRR)
Determine safety and efficacy of tocilizumab in the treatment of IRR/CRS as measured by incidence of IRR/CRS
Measured: During study drug administration (up to 8 months)
Number of Patients With Cytokine Release Syndrome (CRS)
Measured: up to 9 months
Maximum Serum Concentration of Flotetuzumab
Measure the pharmacokinetics (PK) of flotetuzumab
Measured: Study day 1, then every 28 days and 28 days after the last dose (up to 8 months)
Post-baseline Transfusion Independence Rate
The number of patients who were transfusion-dependent at baseline and did not receive transfusions during any consecutive 56-day period will be calculated. The number of patients who are transfusion independent at baseline and remain independent during any 56-day post-baseline period will also be calculated.
Measured: 56 days
Number of Patients Alive at 6 Months
Measured: 6 months
Event-free Survival
Time from the first dose of study drug until date of evidence of primary refractory disease to flotetuzumab, relapse from CR, CRh or CRi, or death from any cause, whichever occurs first.
Measured: Up to 2 years
Mortality Rate
number of deaths from any cause within 30, 60, 90, or 180 days of first dose of study drug
Measured: Throughout the study, up to 3 years.
Number of Patients Alive at 12 Months
Number of patients alive at 1 year from first dose of study drug
Measured: 1 year
Median Time to Response
Time from first dose of study drug to first CR, CRh, CRi, or MLFS
Measured: up to 14 months
Duration of Response of Patients With CR or CRh
Time of initial documentation of response to the time of disease relapse or death due to any cause, whichever occurs first.
Measured: Up to 2 years
Overall Survival
Time from first dose to death from any cause
Measured: Up to 2 years
Rate of Hospitalization for Patients in the Expansion Cohort After Initial Discharge
Initial dosing procedures were performed as a hospital inpatient. Incidence rate of hospitalization after discharge from the hospital will be calculated
Measured: up to 8 months
Duration of Hospitalization for Patients in the Expansion Cohort
Duration of hospitalization will be characterized after discharge from initial dosing will be characterized
Measured: up to 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2014 (estimated)
- Study start9 Jun 2014
- Primary completion5 Jul 2022
- Study completion5 Jul 2022
Why it stopped: Business decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AMLStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 244 participants (actual)
Sponsor and investigators
- Lead sponsor
- MacroGenics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ashley L. Ward, MD, Study director, MacroGenics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02152956
- Sponsor's protocol ID
- CP-MGD006-01
- Acronym
- VOYAGE
- Status last verified
- Jan 2024
- First submitted
- 28 May 2014
- Last updated
- 30 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Expanded access
- Available
Publications
Uy GL, Aldoss I, Foster MC, Sayre PH, Wieduwilt MJ, Advani AS, Godwin JE, Arellano ML, Sweet KL, Emadi A, Ravandi F, Erba HP, Byrne M, Michaelis L, Topp MS, Vey N, Ciceri F, Carrabba MG, Paolini S, Huls GA, Jongen-Lavrencic M, Wermke M, Chevallier P, Gyan E, Recher C, Stiff PJ, Pettit KM, Lowenberg B, Church SE, Anderson E, Vadakekolathu J, Santaguida M, Rettig MP, Muth J, Curtis T, Fehr E, Guo K, Zhao J, Bakkacha O, Jacobs K, Tran K, Kaminker P, Kostova M, Bonvini E, Walter RB, Davidson-Moncada JK, Rutella S, DiPersio JF. Flotetuzumab as salvage immunotherapy for refractory acute myeloid leukemia. Blood. 2021 Feb 11;137(6):751-762. doi: 10.1182/blood.2020007732.
PubMed 32929488
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02152956
- Acronym / sponsor ID
- VOYAGE / CP-MGD006-01
- Conditions
- AML
- Keywords
- AML, leukemia, myelogenous, myeloid, refractory
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business decision
- Enrolment
- 244 participants (actual)
- Lead sponsor
- MacroGenicsIndustry (pharma, biotech, devices)
- Study start
- 9 Jun 2014 (actual)
- Primary completion
- 5 Jul 2022 (actual)
- Study completion
- 5 Jul 2022 (actual)
- First posted
- 2 Jun 2014 (estimated)
- Results
- Posted 30 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 (closed). 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.
Patients will receive daily increasing doses of flotetuzumab for the first week of Cycle 1 (Lead-In Dosing) followed by 3 weeks of continuous intravenous infusion at a the assigned dose. Subsequent cycles are each 4 weeks of continuous infusion at the assigned dose. Dosing may continue for up to 8 cycles. Follow up visits may continue for 6 months after treatment is discontinued.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 13
| Arm | Type | Receives |
|---|---|---|
| Cohort 0-a | Experimental | Biological: Flotetuzumab 3 ng/kg/day, 4 days on and 3 days off |
| Cohort 0-b | Experimental | Biological: Flotetuzumab 10 ng/kg/day, 4 days on and 3 days off |
| Cohort 0-c | Experimental | Biological: Flotetuzumab 30 ng/kg/day, 4 days on and 3 days off |
| Cohort 0-d | Experimental | Biological: Flotetuzumab 100 ng/kg/day, 4 days on and 3 days off |
| Cohort 1 | Experimental | Biological: Flotetuzumab 300 ng/kg/day, 4 days on 3 days off, after one-step lead-in dose |
| Cohort 2 | Experimental | Biological: Flotetuzumab 500 ng/kg/day, 4 days on 3 days off, after one-step lead-in dose |
| Cohort 2a | Experimental | Biological: Flotetuzumab 500 ng/kg/day, continuous infusion, after multi-step lead-in dose |
| Cohort 3 | Experimental | Biological: Flotetuzumab 700 ng/kg/day, 4 days on 3 days off, after multi-step lead-in dose |
| Cohort 6 | Experimental | Biological: Flotetuzumab 300 ng/kg/day, continuous infusion, after multi-step lead-in dose |
| Cohort 7 | Experimental | Biological: Flotetuzumab 500 ng/kg/day, continuous infusion, after multi-step lead-in dose |
| Cohort 8 | Experimental | Biological: Flotetuzumab 700 ng/kg/day, continuous infusion, after multi-step lead-in dose |
| MTD Expansion | Experimental | Biological: Flotetuzumab 500 ng/kg/day, continuous infusion, after multi-step lead-in dose |
| MTD expansion with Ruxolitinib | Experimental | Biological: Flotetuzumab 500 ng/kg/day, continuous infusion, after multi-step lead-in dose, Drug: Ruxolitinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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:
- Limit of 3 prior lines of therapy (excluding focal radiation therapy for palliative purposes): 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
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Flotetuzumab 3 ng/kg/day, 4 days on and 3 days offAlso: MGD006Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART® molecule. | Biological | Cohort 0-a |
| Flotetuzumab 10 ng/kg/day, 4 days on and 3 days offAlso: MGD006Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule. | Biological | Cohort 0-b |
| Flotetuzumab 30 ng/kg/day, 4 days on and 3 days offAlso: MGD006Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule. | Biological | Cohort 0-c |
| Flotetuzumab 100 ng/kg/day, 4 days on and 3 days offAlso: MGD006Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule. | Biological | Cohort 0-d |
| Flotetuzumab 300 ng/kg/day, 4 days on 3 days off, after one-step lead-in doseAlso: MGD006Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule. | Biological | Cohort 1 |
| Flotetuzumab 500 ng/kg/day, 4 days on 3 days off, after one-step lead-in doseAlso: MGD006Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART® molecule. | Biological | Cohort 2 |
| Flotetuzumab 500 ng/kg/day, continuous infusion, after multi-step lead-in doseAlso: MGD006Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule. | Biological | Cohort 2a, Cohort 7, MTD Expansion, MTD expansion with Ruxolitinib |
| Flotetuzumab 700 ng/kg/day, 4 days on 3 days off, after multi-step lead-in doseAlso: MGD006Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule. | Biological | Cohort 3 |
| Flotetuzumab 700 ng/kg/day, continuous infusion, after multi-step lead-in doseAlso: MGD006Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule. | Biological | Cohort 8 |
| RuxolitinibAlso: JakafiOral inhibitor of JAK kinase | Drug | MTD expansion with Ruxolitinib |
| Flotetuzumab 300 ng/kg/day, continuous infusion, after multi-step lead-in doseFlotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule. | Biological | Cohort 6 |
Primary outcome
Efficacy Based on CR or CRh Rate
Time frame: up to 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. CR is defined as mCR, CRc, CRm or CRh. mCR is defined as: normal. neutrophil and platelet counts, less than 5% blast cells in a bone marrow (BM) smear and. no extramedullary disease. CRc is defined as: CR with no evidence of cytogenetic abnormalities in the bone marrow. CRm is defined as: CR with no evidence of molecular abnormalities in the bone marrow. CRh is defined as: CR with partial hematologic recovery.
22 secondary outcomes
Overall Complete Response Rate
Time frame: up to 14 months
CR Rate
Time frame: up to 14 months
CRh Rate
Time frame: up to 14 months
Overall Response Rate
Time frame: up to 14 months
HSCT Rate
Time frame: up to 8 months
Occurrence of Dose Limiting Toxicity
Time frame: Cycle 1 of a 28 day cycle.
Occurrence of Adverse Events (AEs)
Time frame: up to 9 months
Occurrence of Serious Adverse Events (SAEs)
Time frame: up to 9 months
Participants With Anti-drug Antibodies
Time frame: Study Day 1, then every 28 days through 28-days after the last dose (up to 8 months)
Number of Patients With Infusion Related Reaction (IRR)
Time frame: During study drug administration (up to 8 months)
Number of Patients With Cytokine Release Syndrome (CRS)
Time frame: up to 9 months
Maximum Serum Concentration of Flotetuzumab
Time frame: Study day 1, then every 28 days and 28 days after the last dose (up to 8 months)
Post-baseline Transfusion Independence Rate
Time frame: 56 days
Number of Patients Alive at 6 Months
Time frame: 6 months
Event-free Survival
Time frame: Up to 2 years
Mortality Rate
Time frame: Throughout the study, up to 3 years.
Number of Patients Alive at 12 Months
Time frame: 1 year
Median Time to Response
Time frame: up to 14 months
Duration of Response of Patients With CR or CRh
Time frame: Up to 2 years
Overall Survival
Time frame: Up to 2 years
Rate of Hospitalization for Patients in the Expansion Cohort After Initial Discharge
Time frame: up to 8 months
Duration of Hospitalization for Patients in the Expansion Cohort
Time frame: up to 8 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32929488Uy GL, Aldoss I, Foster MC, Sayre PH, Wieduwilt MJ, Advani AS, Godwin JE, Arellano ML, Sweet KL, Emadi A, Ravandi F, Erba HP, Byrne M, Michaelis L, Topp MS, Vey N, Ciceri F, Carrabba MG, Paolini S, Huls GA, Jongen-Lavrencic M, Wermke M, Chevallier P, Gyan E, Recher C, Stiff PJ, Pettit KM, Lowenberg B, Church SE, Anderson E, Vadakekolathu J, Santaguida M, Rettig MP, Muth J, Curtis T, Fehr E, Guo K, Zhao J, Bakkacha O, Jacobs K, Tran K, Kaminker P, Kostova M, Bonvini E, Walter RB, Davidson-Moncada JK, Rutella S, DiPersio JF. Flotetuzumab as salvage immunotherapy for refractory acute myeloid leukemia. Blood. 2021 Feb 11;137(6):751-762. doi: 10.1182/blood.2020007732.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ashley L. Ward, MD study director
MacroGenics
43 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Flotetuzumab 3 ng/kg/day, 4 days on and 3 days off, Flotetuzumab 10 ng/kg/day, 4 days on and 3 days off and Flotetuzumab 30 ng/kg/day, 4 days on and 3 days off in people with AML, run by MacroGenics at 43 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 43 sites in United States, Germany, France, Italy, Israel and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy Based on CR or CRh Rate (time frame: up to 14 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02152956, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2024.