Post-transplant Flotetuzumab for AML

NCT05506956 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: J21134IRB00235421P01CA015396
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to determine if the study drug, flotetuzumab, is safe and tolerable when given to participants with acute myeloid leukemia (AML) that has relapsed after transplant.

Conditions

Leukemia, Myeloid, Acute

Keywords

CD123; AML

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose-limiting Toxicities to Determine Maximum Tolerated Dose (MTD) of Flotetuzumab in Patients With Relapsed/Refractory AML Following alloHSCT

  Number of participants with dose-limiting toxicities (DLTs) at specified dose levels to determine MTD

  6 months

Secondary Outcomes (6)

• Complete Response to Flotetuzumab in Patients With Relapsed AML Following Allogeneic Hematopoietic Stem Cell Transplant (alloHSCT)

  6 months

• Complete Response With Incomplete Count Recovery to Flotetuzumab in Patients With Relapsed AML Following alloHSCT

  6 months

• Partial Response to Flotetuzumab in Patients With Relapsed AML Following alloHSCT

  6 months

• Acute Graft-versus-host Disease (GVHD) Incidence

  6 months

• Chronic GVHD Incidence

  6 months

Study Arms (1)

Flotetuzumab Following Allogeneic Transplant

EXPERIMENTAL

All participants will receive one cycle (28 days) of flotetuzumab. After one cycle, all participants will undergo a bone marrow biopsy to assess response and based on the response, may receive additional cycles up to a total cycle of six cycles.

Drug: Flotetuzumab

Interventions

Flotetuzumab DRUG

Patients enrolled on dose level 1 (DL1) will receive flotetuzumab by continuous infusion using multi-step lead-in dosing, and then 500 ng/kg/day on days 7-28. After one cycle, all patients will undergo a bone marrow biopsy to assess response including assessment of minimal residual disease (MRD). Patients who fail to achieve a CR, CRi, CRh (complete remission with partial hematologic recovery), or MLFS may continue with subsequent induction cycles as a continuous infusion up to a total of five cycles. If there is evidence of response (CR, CRi, CRh, or MLFS) and the toxicities of treatment are acceptable, patients will be eligible for two consolidation cycles. Additional bone marrow biopsies for response assessment will be performed after the second cycle. If there is a need to de-escalate dosing based on toxicity, then patients will be enrolled on DL-1 using multi-step lead-in dosing, and then 300 ng/kg/day on days 5-28 of the first cycle and days 1-28 of subsequent cycles.

Flotetuzumab Following Allogeneic Transplant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A confirmed prior diagnosis of AML and underwent an alloHSCT as a form of consolidation in a morphologic complete remission
• ECOG performance status 0-2
• Ability to give informed consent
• In agreement to use an effective barrier method of birth control to avoid pregnancy during the study and for a minimum of 30 days after study treatment, for all male and female patients who are fertile
• Age ≥18 years
• Prior treatment with a CD123-targeted therapy will be allowed assuming the patient did not have a grade 3 or 4 adverse reaction to prior use of this treatment
• Normal thyroid function (defined by either a thyroid-stimulating hormone (TSH) within the reference range, a TSH above the reference range with a free T4 within the reference range, or a TSH below the reference range with both a free T4 and total T3 within the reference range) or normal thyroid tests on supplementation or treatment (defined as a TSH within the reference range)
• Patients should be at least 30 days from transplant with morphologic evidence of disease progression on bone marrow biopsy
• The presence of a CD123+ AML must be confirmed by flow cytometry with \>1% CD123 AML blasts
• Peripheral blast count ≤20,000/mm3 at time of initiation on Cycle 1 Day 1

You may not qualify if:

• No evidence of donor engraftment (100% patient DNA in bone marrow or peripheral blood after alloHSCT based on either an unsorted specimen or CD3 sorted).
• Active AML in central nervous system (CNS) or testes
• Patients with active, uncontrolled infection. If an infection is controlled and under treatment, then the patient may become eligible.
• Patients with active acute or chronic GVHD requiring GVHD therapy (mycophenolate mofetil, tacrolimus, sirolimus, or steroids) within 30 days
• Patients without active acute or chronic GVHD requiring prophylactic GVHD therapy (mycophenolate mofetil, tacrolimus, sirolimus, or steroids) within 30 days
• Inadequate end organ function defined as:
• Hepatic-AST, ALT, and alkaline phosphatase \> 3.5X upper limit of normal (ULN), bilirubin \>2.5X ULN
• Renal-creatinine clearance \<60 mL/min using the modified Cockcroft-Gault formula
• Cardiac-Recent myocardial infarction within 6 months, Congestive Heart Failure with ejection fraction (EF) \<50%, active pericarditis or myocarditis
• Pulmonary-Need for supplemental oxygen to maintain oxygen saturation \>92%
• Adrenal-Adrenal insufficiency requiring physiologically-dosed steroids
• Women who are pregnant or lactating
• Previous or known hypersensitivity to biological agents or constituents of flotetuzumab or its source material
• Concurrent use of any other investigational drugs
• Uncontrolled infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus (HCV)

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• MacroGenics: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Kristen Murray, Program Manager
• Organization: Johns Hopkins University

kmeckel2@jhmi.edu

410-614-6707

Study Officials

• Jonathan Webster, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2022
• First Posted: August 18, 2022
• Study Start: October 20, 2022
• Primary Completion: June 18, 2024
• Study Completion: June 18, 2024
• Last Updated: September 12, 2025
• Results First Posted: September 12, 2025

Record last verified: 2025-08

Locations

US (1)