Post-transplant Flotetuzumab for AML

August 22, 2025 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

A Phase Ib to Investigate the CD123-targeted DART Flotetuzumab Following Allogeneic Transplant for Patients With CD123+ Acute Myeloid Leukemia

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Despite significant advances, the prognosis for patients with AML remains poor with 5-year overall survival of just ~40% in younger patients and much poorer long-term survival in older patients. Allogeneic hematopoietic stem cell transplantation (AlloHSCT) as post-remission therapy has led to improved overall survival when compared to consolidation chemotherapy for the vast majority of AML patients who have intermediate or poor risk cytogenetics. Due to significant transplant-related mortality (TRM) and poor outcomes in older patients with myeloablative conditioning (MAC) transplantation, there have been many studies investigating the feasibility of less intensive conditioning regimens such as reduced-intensity conditioning (RIC) and nonmyeloablative (NMA), which have shown comparable overall survival with decreased TRM but an increased risk of relapse. As these less intensive conditioning strategies become more widely adopted, the need to focus on the identification and treatment of AML patients at risk for post-transplant relapse increases. Maintenance therapy with tyrosine kinase inhibitors and monoclonal antibodies have proven safe and effective across a range of diseases including AML, acute lymphocytic leukemia (ALL), and non-Hodgkin's lymphoma (NHL). Leukemia stem cells (LSCs) are another potential target for post-transplant therapy, and the expression of CD123 readily discriminates AML LSCs from hematopoietic stem cells (HSCs). The anti-CD123 monoclonal antibody CSL360 has previously demonstrated efficacy in post-transplant patients with relapsed disease, while flotetuzumab has demonstrated efficacy in relapsed and refractory patients. Given this preliminary data, the investigators propose a trial of flotetuzumab as post-alloHSCT therapy for AML in patients with evidence of disease post-transplant including frank relapse. The investigators believe that treatment with flotetuzumab in this setting will be well tolerated and effective. Flotetuzumab is not approved for use in people with AML. Its use has not been specifically studied in patients with AML following a bone marrow transplant and therefore its use in this study is investigational.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
3

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. A confirmed prior diagnosis of AML and underwent an alloHSCT as a form of consolidation in a morphologic complete remission
  2. ECOG performance status 0-2
  3. Ability to give informed consent
  4. 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
  5. Age ≥18 years
  6. 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
  7. 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)
  8. Patients should be at least 30 days from transplant with morphologic evidence of disease progression on bone marrow biopsy
  9. The presence of a CD123+ AML must be confirmed by flow cytometry with >1% CD123 AML blasts
  10. Peripheral blast count ≤20,000/mm3 at time of initiation on Cycle 1 Day 1

Exclusion Criteria:

  1. 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).
  2. Active AML in central nervous system (CNS) or testes
  3. Patients with active, uncontrolled infection. If an infection is controlled and under treatment, then the patient may become eligible.
  4. Patients with active acute or chronic GVHD requiring GVHD therapy (mycophenolate mofetil, tacrolimus, sirolimus, or steroids) within 30 days
  5. Patients without active acute or chronic GVHD requiring prophylactic GVHD therapy (mycophenolate mofetil, tacrolimus, sirolimus, or steroids) within 30 days

  6. 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
  7. Women who are pregnant or lactating
  8. Previous or known hypersensitivity to biological agents or constituents of flotetuzumab or its source material
  9. Concurrent use of any other investigational drugs
  10. Uncontrolled infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus (HCV)
  11. Any active untreated autoimmune disorders (with the exception of vitiligo, resolved childhood atopic dermatitis, prior Grave's disease now euthyroid clinically with stable supplementation)
  12. Previous treatment with radiotherapy or an immunotherapeutic agent in the 14 days prior to study drug administration (Cycle 1 Day 1) or 5 half-lifes, whichever is longer
  13. Requirement, at the time of study entry, for concurrent steroids > 10 mg/day of oral prednisone or equivalent, except steroid inhaler, nasal spray, or ophthalmic solution
  14. Use of granulocyte colony stimulating or granulocyte-macrophage colony stimulating factor in the 2 weeks prior to study drug administration
  15. Prior adverse event with CD123 therapy necessitating therapy discontinuation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Flotetuzumab Following Allogeneic Transplant
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
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Dose-limiting Toxicities to Determine Maximum Tolerated Dose (MTD) of Flotetuzumab in Patients With Relapsed/Refractory AML Following alloHSCT
Time Frame: 6 months
Number of participants with dose-limiting toxicities (DLTs) at specified dose levels to determine MTD
6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Complete Response to Flotetuzumab in Patients With Relapsed AML Following Allogeneic Hematopoietic Stem Cell Transplant (alloHSCT)
Time Frame: 6 months
Number of participants with complete response (CR) following alloHSCT.
6 months
Complete Response With Incomplete Count Recovery to Flotetuzumab in Patients With Relapsed AML Following alloHSCT
Time Frame: 6 months
Number of participants with complete response with incomplete count recovery (CRi) following allogeneic hematopoietic stem cell transplant (alloHSCT).
6 months
Partial Response to Flotetuzumab in Patients With Relapsed AML Following alloHSCT
Time Frame: 6 months
Number of participants with partial response (PR) following allogeneic hematopoietic stem cell transplant (alloHSCT).
6 months
Acute Graft-versus-host Disease (GVHD) Incidence
Time Frame: 6 months
Number of safety events defined as CTCAE grade III-IV acute GVHD.
6 months
Chronic GVHD Incidence
Time Frame: 6 months
Number of events of chronic GVHD requiring systemic immune suppression
6 months
Non-relapse Mortality
Time Frame: through study completion, an average of 1 year 8 months
Number of participant deaths without recurrent or progressive disease after allo-HSCT.
through study completion, an average of 1 year 8 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)
MacroGenics

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jonathan Webster, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 20, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 18, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 18, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 16, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 16, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 18, 2022

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 12, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 22, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • J21134
  • P01CA015396 (U.S. NIH Grant/Contract)
  • IRB00235421 (Other Identifier: JHMIRB)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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