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Recurrent Acute Myeloid LeukemiaPhase 1NCT04158739

Flotetuzumab for the Treatment of Pediatric Recurrent or Refractory Acute Myeloid Leukemia

A Phase 1 study testing Cytarabine and Flotetuzumab in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by Children's Oncology Group at 19 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase I trial studies the side effects, best dose of flotetuzumab and how well it works in treating patients with acute myeloid leukemia (AML) that has come back (recurrent) or has not responded to treatment (refractory). This study also determines the safest dose of flotetuzumab to use in children with AML. Read more about this study

Who is it for?
Ages Up to 20 years
What is being tested?
Cytarabine and Flotetuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
19 sitesUnited States
Study dates
22 Jan 2020to 31 Mar 2027
Phase
Phase 1
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 Up to 20 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patients must weigh >/= 17 kg
  • Weight limit is due to constraints related to the concentration of the current drug formulation. If a new formulation of flotetuzumab becomes available to allow dosing of smaller patients, the protocol will be amended.
  • Patients with recurrent or refractory AML are eligible. Patients must have histologic verification of malignancy at relapse.
  • Patients with leukemia must have >/= M2 marrow by morphology and/or flow cytometry and one of the following:
  • Second or greater relapse
  • Refractory after 2 or more chemotherapy cycles
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  • First relapse after primary chemotherapy-refractory disease
  • First relapse after hematopoietic stem cell transplantation (HSCT)
  • Central nervous system (CNS) disease:
  • Patients must have the status of CNS1 and no clinical signs or neurologic symptoms suggestive of CNS leukemia, such as cranial palsy.
  • Patients with CNS3 or CNS2 status may receive antecedent intrathecal chemotherapy to achieve CNS1 status prior to study entry.
  • Patients with a history of CNS chloromatous disease are required to have no radiographic evidence of disease prior to enrollment.
  • Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =/< 16 years of age. Use appropriate score for study population. NOTE: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
  • Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately.
  • Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive.
  • >/= 14 days must have elapsed after the completion of other cytotoxic therapy with the exception of hydroxyurea. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy.
  • NOTE: Cytoreduction with hydroxyurea is recommended to be discontinued >/= 24 hours prior to the start of protocol therapy. No waiting period is required for patients having received intrathecal cytarabine, methotrexate, and/or hydrocortisone.
  • Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count [ANC] counts): >/= 7 days after the last dose of agent.
  • Antibodies: >/= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =/< 1.
  • Corticosteroids: If used to modify immune adverse events related to prior therapy, >/= 14 days must have elapsed since last dose of corticosteroid.
  • Hematopoietic growth factors: >/= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator.
  • Interleukins, interferons and cytokines (other than hematopoietic growth factors): >/= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors).
  • Stem cell infusions (with or without total body irradiation [TBI]):
  • Allogeneic (non-autologous) bone marrow or stem cell transplant, or stem cell boost: >/= 84 days after infusion and no evidence of graft versus host disease (GVHD)
  • Donor leukocyte infusion: >/= 42 days
  • Autologous stem cell infusion including boost infusion: >/= 42 days
  • Cellular therapy: >/= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
  • Radiation therapy (XRT)/external beam irradiation including protons: >/= 14 days after local XRT; >/= 84 days after TBI, craniospinal XRT or if radiation to >/= 50% of the pelvis; >/= 42 days if other substantial bone marrow (BM) radiation
  • Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >/= 42 days after systemically administered radiopharmaceutical therapy
  • Patients must not have received prior exposure to flotetuzumab.
  • Platelet count >/= 20,000/mm^3 (may receive platelet transfusions)
  • These patients must not be known to be refractory to red cell or platelet transfusion
  • Hemoglobin >/= 8.0 g/dL at baseline (may receive red blood cell [RBC] transfusions)
  • These patients must not be known to be refractory to red cell or platelet transfusion.
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >/= 70 ml/min/1.73 m^2 or
  • A serum creatinine based on age/gender as follows:
  • Age: Maximum serum creatinine (mg/dL)
  • 1 to < 2 years: male - 0.6; female - 0.6
  • 2 to < 6 years: male - 0.8; female - 0.8
  • 6 to < 10 years: male - 1; female - 1
  • 10 to < 13 years: male - 1.2; female - 1.2
  • 13 to < 16 years: male - 1.5; female - 1.4
  • >/= 16 years: male - 1.7; female - 1.4
  • Bilirubin (sum of conjugated + unconjugated) =/< 1.5 x upper limit of normal (ULN) for age regardless of baseline
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =/< 3 x ULN. For the purpose of this study, the ULN for SGPT is 45 U/L regardless of baseline.
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST/< 3 x ULN. For the purpose of this study, the ULN for SGPT is 50 U/L regardless of baseline.
  • Serum albumin >/= 2 g/dL
  • Shortening fraction of >/= 27% by echocardiogram, or
  • Ejection fraction of >/= 50% by gated radionuclide study
  • Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
  • Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5) resulting from prior therapy must be =/< grade 2 with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible.
  • All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
  • Permanent central access should be established with a central line. A central line that contains 2 lumens is preferred.

Who cannot join

  • Pregnant or breast-feeding women will not be entered on this study because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy and for 12 weeks after flotetuzumab discontinuation.
  • Patients must be off steroids (unless physiologic replacement dosing) for at least 7 days prior to enrollment. If used to modify immune adverse events related to prior therapy, >/= 14 days must have elapsed since last dose of corticosteroid.
  • Patients who are currently receiving another investigational drug are not eligible.
  • Patients who are currently receiving other anti-cancer agents are not eligible (except hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy).
  • Patients who are receiving cyclosporine, tacrolimus or other agents to treat graft-versus-host disease post bone marrow transplant are not eligible for this trial.
  • Patient has French-American-British classification (FAB) type M3 leukemia (acute promyelocytic leukemia) or identification of t(15;17).
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  • Patient has isolated CNS involvement or isolated extramedullary relapse.
  • Patient with known human immunodeficiency virus (HIV) infection are eligible if he or she has a negative HIV serology and an undetectable viral load.
  • Patient known to have one of the following concomitant genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome or any other known bone marrow failure syndrome. Patients with Down syndrome are eligible for the study.
  • Patients must not weigh < 17 kg.
  • Patients must not have received prior therapy with a CD123 directed antibody or CD123 directed chimeric antigen receptor (CAR) T cells.
  • Patients who have an uncontrolled infection are not eligible.
  • Patients who have received a prior solid organ transplantation are not eligible.
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
  • Known hypersensitivity to murine, yeast, or recombinant proteins; polysorbate 80; recombinant human serum albumin; benzyl alcohol; or any excipient contained in the flotetuzumab drug formulation. Additionally, those patients who have had a hypersensitivity reaction to etoposide that is considered likely related to polysorbate 80 are not eligible.
  • Patients must refrain from driving a motor vehicle or operating heavy machinery while receiving flotetuzumab and for 30 days from the date of last study drug administration.

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

United States19 sites

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Children's Healthcare of Atlanta - Arthur M Blank Hospital

    Atlanta, Georgia, 30329

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Saint Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • UCSF Medical Center-Mission Bay

    San Francisco, California, 94158

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

Official title: A Phase 1 Trial of the CD123 X CD3 DART Molecule Flotetuzumab (NSC#808294) in Children, Adolescents, and Young Adults With Relapsed or Refractory Acute Myeloid Leukemia

This phase I trial studies the side effects, best dose of flotetuzumab and how well it works in treating patients with acute myeloid leukemia (AML) that has come back (recurrent) or has not responded to treatment (refractory). This study also determines the safest dose of flotetuzumab to use in children with AML. As an immunotherapy, flotetuzumab may also cause changes in the body's normal immune system, which are also under study in this trial.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the safety and tolerability of flotetuzumab administered by continuous intravenous (IV) infusion to pediatric patients < 21 years of age with relapsed or refractory acute myeloid leukemia (AML).

II. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of flotetuzumab administered by continuous IV infusion to pediatric patients < 21 years of age with relapsed or refractory AML.

SECONDARY OBJECTIVES:

  1. To characterize the pharmacokinetics of flotetuzumab in pediatric patients with relapsed or refractory AML.

II. To preliminarily define the anti-tumor activity of flotetuzumab within the confines of a phase 1 study and correlate potential activity with baseline disease burden at study entry.

III. To monitor anti-drug antibody (ADA) production and characterize the immunogenicity of flotetuzumab.

EXPLORATORY OBJECTIVES:

  1. To evaluate changes in T-lymphocyte population numbers before and after flotetuzumab treatment.

II. To evaluate the tumor microenvironment and cytokine production by immune effector cells before and after flotetuzumab treatment.

III. To quantify CD123 surface expression on AML cells at baseline and evaluate expression as a potential biomarker of flotetuzumab response.

OUTLINE: This is a dose-escalation/dose de-escalation study of flotetuzumab.

Patients receive cytarabine intrathecally (IT) on days -6 to 0 prior to cycle 1. Patients may receive additional doses of cytarabine on day 1 of subsequent cycles per physician discretion. Patients also receive flotetuzumab IV continuously for 28 days. Treatment repeats every 29 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 30 days.

Being tested
Cytarabine, Flotetuzumab
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CytarabineDrug

    Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone

    Given IT

  • FlotetuzumabBiological

    Also called CD123 x CD3 DART Bi-Specific Antibody MGD006, CD123 x CD3 Dual Affinity Re-Targeting Bi-Specific Antibody MGD006, MGD006, RES234

    Given IV

Study groups in NCT04158739
Study groupRoleWhat they receive
Treatment (cytarabine, flotetuzumab)ExperimentalPatients receive cytarabine IT on days -6 to 0 prior to cycle 1. Patients may receive additional doses of cytarabine on day 1 of subsequent cycles per physician discretion. Patients also receive flotetuzumab IV continuously for 28 days. Treatment repeats every 29 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Cytarabine; Biological: Flotetuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Limiting Toxicities Due to Flotetuzumab

    Number and percentage of patients experiencing dose limiting toxicities during cycle 1 that are possibly, probably, or definitely due to flotetuzumab by dose level and study part.

    Measured: Up to 29 days

  2. Maximum Tolerated Dose or Recommended Phase 2 Dose of Flotetuzumab

    Estimated maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of Flotetuzumab defined by the maximum dose at which fewer than one-third of toxicity-evaluable participants experience a DLT. RP2D was established by study committee based off the toxicity profile of DL1 (500 ng/kg/day).

    Measured: Up to 29 days

Secondary outcomes (2)

  1. Maximum Concentration (C Max)

    Median with Minimum and Maximum for the maximum (peak) serum concentration measured on days 3-9 post-administration by dose level and study part.

    Measured: Up to 9 days

  2. Antitumor Activity of Flotetuzumab

    Number of response evaluable participants with response (CR/PR) using revised AML International Working Group criteria for response including CR: M1 bone marrow (<5% blasts), ANC at least 1000/mm3 and platelet count at least 100,000/mm3; CRp: platelet transfusion independence; CRi: without platelet transfusion independence, CRc: revision to normal karyotype; PR: decrease at least 50% in percentage of blasts to 5% to 25% in bone marrow aspirate.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Nov 2019
  2. Study start22 Jan 2020
  3. Primary completion30 Sep 2022
  4. Study completion31 Mar 2027 (estimated)

Resources

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04158739
Sponsor's protocol ID
PEPN1812
Other IDs
NCI-2019-06780, PEPN1812, PEPN1812, UM1CA228823
Status last verified
Aug 2026
First submitted
15 Oct 2019
Last updated
24 Aug 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cytarabine and Flotetuzumab in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by Children's Oncology Group at 19 sites in United States.

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 54 inclusion and 16 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: under way, not looking for participants, as of the sponsor's last update on 24 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. 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 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.

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 11 Dec 2023). 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?

Dose Limiting Toxicities Due to Flotetuzumab (time frame: Up to 29 days). The study lists 2 primary outcomes in all. 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 NCT04158739.

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 24 Aug 2026.

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