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NCT04582864

Flotetuzumab for Relapsed Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Following Allogeneic Hematopoietic Cell Transplantation (Allo-HCT)

Terminated Phase 2 Results posted Last updated 6 December 2024
What this trial tests

Phase 2 trial testing Flotetuzumab in Relapsed Acute Myeloid Leukemia in 11 participants. Terminated before completion.

Timeline
20 May 2021
Primary endpoint
29 March 2024
26 July 2024

Quick facts

Lead sponsorWashington University School of Medicine
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment11
Start date20 May 2021
Primary completion29 March 2024
Estimated completion26 July 2024
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Washington University School of Medicine

Who can join

18 and older, any sex, with Relapsed Acute Myeloid Leukemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Efficacy as Measured by Number of Participants With CR(Mrd), CR, and CRi Primary · At the end of Cycle 1 (each cycle is 28 days)

* Complete remission without minimal residual disease (CRmrd): CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFC * Complete remission (CR): Bone marrow blasts \<5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC ≥1.0 × 10\^9/L (1000/µL); platelet count ≥100 × 10\^9/L (100,000/µL), transfusion independence * CR with incomplete hematologic recovery (CRi): All CR criteria except for residual neutropenia (\<1.0 × 10\^9/L \[1000/µL\]) or thrombocytopenia (\<100 × 10\^9/L \[100,000/µL\])

GroupValue95% CI
Flotetuzumab0
Efficacy as Measured by Number of Participants With CR and CRi Secondary · At the end of Cycle 2 (each cycle is 28 days)

* Complete remission (CR): Bone marrow blasts \<5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC ≥1.0 × 10\^9/L (1000/µL); platelet count ≥100 × 10\^9/L (100,000/µL), transfusion independence * CR with incomplete hematologic recovery (CRi): All CR criteria except for residual neutropenia (\<1.0 × 10\^9/L \[1000/µL\]) or thrombocytopenia (\<100 × 10\^9/L \[100,000/µL\])

GroupValue95% CI
Flotetuzumab0
Overall Response Rate Secondary · At the end of Cycle 2 (each cycle is 28 days)

* Defined as partial remission or better * PR: All hematologic criteria of CR; decrease of bone marrow blast percentage to 5 to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%

GroupValue95% CI
Flotetuzumab0
Morphologic Leukemia-free State (MLFS) Rate Secondary · At the end of Cycle 2 (each cycle is 28 days)

\- MLFS: Bone marrow blasts \<5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required

GroupValue95% CI
Flotetuzumab0
Partial Remission (PR) Rate Secondary · At the end of Cycle 2 (each cycle is 28 days)

\- PR: All hematologic criteria of CR; decrease of bone marrow blast percentage to 5 to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%

GroupValue95% CI
Flotetuzumab2
Stable Disease (SD) Rate Secondary · At the end of Cycle 2 (each cycle is 28 days)

\- SD: Absence of CR(mrd), CR, CRi, PR, MLFS; and criteria for PD not met

GroupValue95% CI
Flotetuzumab3
Progression-free Survival (PFS) Rate Secondary · Through completion of follow-up, up to 2 years (median length of 80 days, full range of 11-149 days)

* PFS will be calculated as the time from the start of the first dose of study drug until the occurrence of disease progression or death from any cause, respectively * Progressive disease: Evidence for an increase in bone marrow blast percentage (\>50% over baseline), and/or increase of absolute blast counts in the blood (\>50% to \>25 × 10\^9/L) without differentiation syndrome, or new extramedullary disease

GroupValue95% CI
Flotetuzumab1.140.79 – 2.49
Overall Survival (OS) Secondary · Through completion of follow-up, up to 2 years (median length of 80 days, full range of 11-149 days)

-OS will be calculated as the time from the start of the first dose of study drug until the occurrence of death from any cause.

GroupValue95% CI
Flotetuzumab2.661.11 – 4.30
Number of Participants With Adverse Events as Measured by CTCAE v5.0 Secondary · From start of treatment through 28 days following completion of treatment (median length of 59 days, full range 11-99 days).
Grade 3-5 anemia
GroupValue95% CI
Flotetuzumab4
Grade 3-5 febrile neutropenia
GroupValue95% CI
Flotetuzumab3
Grade 1-2 sinus tachycardia
GroupValue95% CI
Flotetuzumab1
Grade 1-2 adrenal insufficiency
GroupValue95% CI
Flotetuzumab1
Grade 1-2 anisocoria
GroupValue95% CI
Flotetuzumab1
Grade 1-2 conjunctivitis
GroupValue95% CI
Flotetuzumab1
Grade 1-2 scleral hemorrhage
GroupValue95% CI
Flotetuzumab1
Grade 1-2 blurred vision
GroupValue95% CI
Flotetuzumab1
Number of Participants With Cytokine Release Syndrome (CRS) Grading as Measured by ASTCT Consensus Guidelines Secondary · Through the end of Cycle 2 (each cycle is 28 days)

* Grade 1:Symptoms are not life threatening and require symptomatic treatment only, e.g., fever, nausea, fatigue, headache, myalgias, malaise * Grade 2: Symptoms require and respond to moderate intervention; oxygen requirement \< 40% or hypotension responsive to fluids or low-dose of one vasopressor or grade 2 organ toxicity * Grade 3: Symptoms require and respond to aggressive intervention; oxygen requirement ≥ 40% or hypotension requiring high-dose vasopressors or multiple vasopressors or grade 3 organ toxicity (except transaminitis) or grade 4 transaminitis * Grade 4: Life-threatening sympt

Grade 1
GroupValue95% CI
Flotetuzumab1
Grade 2
GroupValue95% CI
Flotetuzumab7
Grade 3
GroupValue95% CI
Flotetuzumab3
Grade 4
GroupValue95% CI
Flotetuzumab0
Grade 5
GroupValue95% CI
Flotetuzumab0
Number of Participants With Neurotoxicity as Measured by 2019 ASTCT Consensus Guidelines Secondary · Through the end of Cycle 2 (each cycle is 28 days)
GroupValue95% CI
Flotetuzumab4
Number of Participants With Acute Graft Versus Host Disease (GvHD) as Measured by MAGIC Criteria Secondary · Through completion of follow-up, up to 2 years (median length of 80 days, full range of 11-149 days)
GroupValue95% CI
Flotetuzumab1

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events and serious adverse events were collected from start of treatment through 28 days following discontinuation of flotetuzumab (median length of 59 days, full range 11-99 days). All-cause mortality was collected from start of treatment through completion of protocol defined follow-up (median length of 80 days, full range of 11-149 days).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Flotetuzumab
Serious: 8/11 (73%)
Deaths: 10/11

Serious adverse events (9 terms)

ReactionSystemFlotetuzumab
Disease progressionGeneral disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
Cytokine release syndromeImmune system disorders
GvHD of the gutImmune system disorders
SepsisInfections and infestations
SinusitisInfections and infestations
DehydrationMetabolism and nutrition disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Other adverse events (131 terms — click to expand)

ReactionSystemFlotetuzumab
FeverGeneral disorders
Cytokine release syndromeImmune system disorders
Lymphocyte count decreasedInvestigations
HypocalcemiaMetabolism and nutrition disorders
FatigueGeneral disorders
White blood cell decreasedInvestigations
HypoalbuminemiaMetabolism and nutrition disorders
HypophosphatemiaMetabolism and nutrition disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Blood bilirubin increasedInvestigations
DiarrheaGastrointestinal disorders
Neutrophil count decreasedInvestigations
HyperglycemiaMetabolism and nutrition disorders
Alkaline phosphatase increasedInvestigations
INR increasedInvestigations
DyspneaRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
NauseaGastrointestinal disorders
HypotensionVascular disorders
AnemiaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
VomitingGastrointestinal disorders
ChillsGeneral disorders
Generalized edemaGeneral disorders
PainGeneral disorders
HyperphosphatemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
TremorNervous system disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Edema limbsGeneral disorders
MalaiseGeneral disorders
HypernatremiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
Bone painMusculoskeletal and connective tissue disorders
Generalized muscle weaknessMusculoskeletal and connective tissue disorders
Neck painMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Disease progression, Respiratory failure, Febrile neutropenia, Cytokine release syndrome, GvHD of the gut, Sepsis, Sinusitis, Dehydration.

Data from ClinicalTrials.gov NCT04582864 adverse events section.

Sponsor's own description

The investigators hypothesize that flotetuzumab for relapsed AML following allo-HCT will be safe, tolerable and may facilitate preferential immune effector cell retargeting of leukemic cells resulting in improved patient outcomes. Furthermore, administration of a donor lymphocyte infusion (DLI) (if available) in combination with flotetuzumab will be safe, tolerable and may provide additional therapeutic efficacy.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Antibodies to watch in 2021.
    Kaplon H, Reichert JM. · · 2021 · cited 215× · PMID 33459118 · DOI 10.1080/19420862.2020.1860476
  2. Recent advances in targeted therapies in acute myeloid leukemia.
    Bhansali RS, Pratz KW, Lai C. · · 2023 · cited 151× · PMID 36966300 · DOI 10.1186/s13045-023-01424-6
  3. Regulation and signaling pathways in cancer stem cells: implications for targeted therapy for cancer.
    Zeng Z, Fu M, Hu Y, Wei Y, et al · · 2023 · cited 93× · PMID 37853437 · DOI 10.1186/s12943-023-01877-w
  4. Bispecific Antibodies: A Smart Arsenal for Cancer Immunotherapies.
    You G, Won J, Lee Y, Moon D, et al · · 2021 · cited 39× · PMID 34358141 · DOI 10.3390/vaccines9070724
  5. Bispecific Antibodies in Hematological Malignancies: A Scoping Review.
    Omer MH, Shafqat A, Ahmad O, Alkattan K, et al · · 2023 · cited 34× · PMID 37760519 · DOI 10.3390/cancers15184550
  6. What have we learned about TP53-mutated acute myeloid leukemia?
    Shahzad M, Amin MK, Daver NG, Shah MV, et al · · 2024 · cited 32× · PMID 39562552 · DOI 10.1038/s41408-024-01186-5
  7. The genesis and evolution of acute myeloid leukemia stem cells in the microenvironment: From biology to therapeutic targeting.
    Chen Y, Li J, Xu L, Găman MA, et al · · 2022 · cited 32× · PMID 36163119 · DOI 10.1038/s41420-022-01193-0
  8. Treatment of AML Relapse After Allo-HCT.
    Webster JA, Luznik L, Gojo I. · · 2021 · cited 28× · PMID 34976845 · DOI 10.3389/fonc.2021.812207

Verify or expand the search:

Other trials of Flotetuzumab

Trials testing the same drug.

Other recruiting trials for Relapsed Acute Myeloid Leukemia

Currently open trials in the same condition.

Other Washington University School of Medicine trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04582864.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing