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Recurrent Acute LeukemiaPhase 1NCT04681105

Flotetuzumab for the Treatment of Relapsed or Refractory Advanced CD123-Positive Hematological Malignancies

A Phase 1 study testing Acetaminophen, Dexamethasone and Diphenhydramine in people with Recurrent Acute Leukemia and Recurrent B Acute Lymphoblastic Leukemia, run by City of Hope Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase I trial studies the best dose and side effects of flotetuzumab for the treatment of patients with blood cancers (hematological malignancies) that have spread to other places in the body (advanced) and have come back after a period of improvement (relapsed) or does not respond to treatment (refractory). Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
Acetaminophen, Dexamethasone and Diphenhydramine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
18 Nov 2020to 5 Aug 2025
Phase
Phase 1
Are there results?
None posted in the registry

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 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Documented informed consent of the participant and/or legally authorized representative
  • Assent, when appropriate, will be obtained per institutional guidelines
  • Agreement to allow the use of archival tissue from diagnostic tumor biopsies
  • If unavailable, exceptions may be granted with study principal investigator (PI) approval
  • Eastern Cooperative Oncology Group (ECOG) =< 2
  • Histologically confirmed diagnosis of
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  • Cohort A. Acute lymphoblastic leukemia
  • B-cell phenotype: patients with relapsed or refractory ALL who have received at least 2 prior regimens and failed or are ineligible for CD19-based targeted therapy
  • T-cell phenotype: patients with relapsed or refractory who have received at least 1 prior regimen
  • Cohort B. Other CD123+ hematological malignancies that failed standard regimens, excluding acute myeloid leukemia and myelodysplastic syndrome
  • Blastic plasmacytoid dendritic cell neoplasm (BPDCN) patients who have failed or relapsed after initial therapy
  • Chronic myelocytic leukemia (CML) patients who have failed or relapsed or ineligible for third generation tyrosine kinase inhibitor (ponatinib)
  • Hairy cell leukemia patients who have failed or progressed shortly after purine analogs or failed 2 cycles of purine analog
  • Systemic mastocytosis patients who have failed or progressed on midostaurin
  • Hodgkin lymphoma patients who have failed or relapsed after PD-1/PD-L1- inhibitors and brentuximab vedotin
  • Advanced acute leukemia patients with ambiguous lineage or biphenotypic leukemia that failed 2 lines of prior regimens
  • Patients with any other advanced CD123+ hematological malignancy who have failed standard therapy per the treating physician's judgement
  • Relapsed or refractory disease as defined above
  • Tumor expressing CD123 either by flow cytometry or immunohistochemistry staining
  • Measurable disease of at least 1.5 cm on computed tomography (CT)/magnetic resonance imaging (MRI) for cases without bone marrow involvement
  • Peripheral blast count < 20,000/ul at the time of initiation of infusion on Cycle 1 Day 1
  • Life expectancy of at least 4 weeks
  • Fully recovered from the acute toxic effects (except alopecia) to =< grade 1 to prior anti-cancer therapy
  • Absolute neutrophil count (ANC) >= 1000/ul (without bone marrow involvement, performed within 14 days prior to day 1 of protocol therapy)
  • Platelets >= 75,000/ul (without bone marrow involvement, performed within 14 days prior to day 1 of protocol therapy)
  • Lumbar puncture to assess presence of central nervous system (CNS) disease if there are symptoms and signs concerning for CNS involvement (performed within 14 days prior to day 1 of protocol therapy)
  • Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease) (performed within 14 days prior to day 1 of protocol therapy)
  • Aspartate aminotransferase (AST) =< 2.5 x ULN (performed within 14 days prior to day 1 of protocol therapy)
  • Alanine aminotransferase (ALT) =< 2.5 x ULN (performed within 14 days prior to day 1 of protocol therapy)
  • Left ventricular ejection fraction (LVEF) >= 50%. Note: To be performed within 28 days prior to day 1 of protocol therapy
  • Corrected QT (QTc) =< 480 ms. Note: To be performed within 28 days prior to day 1 of protocol therapy
  • If able to perform pulmonary function tests: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and DLCO (diffusion capacity) >= 50% of predicted (corrected for hemoglobin). If unable to perform pulmonary function tests: oxygen (O2) saturation > 90% on room air. Note To be performed within 28 days prior to day 1 of protocol therapy
  • Calculated or measured creatinine clearance of > 50 ml/min (performed within 14 days prior to Day 1 of protocol therapy)
  • Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required (performed within 14 days prior to day 1 of protocol therapy)
  • Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy
  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Who cannot join

  • Autologous or allogeneic hematopoietic cell transplant performed within 100 days prior to study drug administration in Day 1 of Cycle 1 of protocol therapy
  • However, patients who received allogeneic hematopoietic cell transplantation (HCT) more than 100 days are allowed if no active graft versus host disease (GVHD) > grade 1, not actively on systemic immunosuppressive therapy and off calcineurin inhibitors for at least 4 weeks prior to start therapy
  • Chemotherapy, radiation therapy, biological therapy, within 14 days prior to Day 1 of protocol therapy. Maintenance-type ALL chemotherapies, including vincristine and mercaptopurine are allowed up to 7 days before starting therapy. High dose steroids are allowed up to 3 days before starting therapy. Cytoreduction with hydroxyurea is allowed to control leukocytosis until to the day of starting therapy. Hydroxyurea can be given during cycle 1 of flotetuzumab administration to control leukocytosis but need to be discussed with the study PI
  • Previous treatment with immunotherapeutic agents (for example chimeric antigen receptor [CAR] T cells, long acting bispecific antibodies, etc) in the 28 days period prior to study drug administration on Day 1 Cycle 1, with the exception of short-half bispecific antibodies (blinatumomab) where the washout period is only 14 days
  • Requirement, at the time of study entry, for concurrent steroid > 10 mg/day of oral prednisone or the equivalent, except steroid inhaler, nasal spray or ophthalmic solution
  • Use of immunosuppressant medications (other than steroid as noted above) in the 2 weeks prior to study drug administration (Cycle 1 Day 1)
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  • Known central nervous system involvement. Patients with suspected CNS involvement must be evaluated by lumbar puncture and be free of CNS disease prior to study entry. Previously treated CNS involvement is allowed provided adequate treatment has been provided and the patient is free of CNS disease
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to flotetuzumab
  • Any active untreated autoimmune disorders (with the exception of vitiligo)
  • Dementia or altered mental status that would preclude sufficient understanding to provide informed consent
  • Second primary malignancy that requires active therapy. Adjuvant hormonal therapy is allowed
  • Active uncontrolled infection
  • Significant pulmonary compromise
  • Unstable angina or clinically significant heart disease (left ventricular ejection fraction < 50%)
  • Major trauma or surgery within 4 weeks before enrollment
  • Clinically significant uncontrolled illness
  • Females only: Pregnant or breastfeeding
  • Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: A Phase 1 Trial to Evaluate the Safety of Single Agent Flotetuzumab in Advanced CD123-Positive Hematological Malignancies

This phase I trial studies the best dose and side effects of flotetuzumab for the treatment of patients with blood cancers (hematological malignancies) that have spread to other places in the body (advanced) and have come back after a period of improvement (relapsed) or does not respond to treatment (refractory). Flotetuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (recommended phase 2 dose, RP2D) of flotetuzumab, when given as a single agent.

II. Evaluate the safety and tolerability of flotetuzumab in CD123-positive advanced acute lymphoblastic leukemia (ALL) (Cohort A) and other hematological malignancies (Cohort B), by evaluation of toxicities including: type, frequency, severity, attribution, and duration of the toxicity.

SECONDARY OBJECTIVES:

  1. Obtain preliminary estimates of remission; (complete remission [CR], complete remission with incomplete count recovery [CRi], complete remission with partial hematological recovery [CRh] or morphologic leukemia free state [MLFS] in Cohort A or CR/molecular response [MR] in Cohort B) rate and duration.

II. Estimate 1-year overall survival. III. Evaluate minimal residual disease (MRD) status in responders in the ALL cohort.

IV. Evaluate the percentage of patients who receive subsequent allogeneic transplantation.

EXPLORATORY OBJECTIVES:

  1. Examine immune profile pre- and post-treatment with flotetuzumab. II. Assess the association between CD123 expression and tumor response. III. Assess the association between alterations in tumor genetic or microenvironment with response.

IV. Assess cytokine levels during therapy.

OUTLINE: This is a dose-escalation study.

INDUCTION THERAPY: Patients receive flotetuzumab via continuous intravenous (IV) infusion on days 1-28. Patients who achieve stable disease (SD)/partial remission (PR) (Cohort A) or PR/clinical improvement (CI) (Cohort B), receive an additional induction cycle. Patients who achieve PR (Cohort A) or PR/CI/major molecular response (MMR) (Cohort B) after cycle 2 re-induction, may continue induction therapy for up to 4 more cycles.

CONSOLIDATION THERAPY: Patients who achieve CR/CRi/CRh/MLFS (Cohort A) or CR/MR (Cohort B) after cycle 1 or cycle 2 of induction therapy, receive flotetuzumab via continuous IV infusion on days 1-28 for up to 5 and 6 cycles, respectively, in the absence of disease progression or unacceptable toxicity. Patients with PR (Cohort A) or PR/CI/MMR (Cohort B) who have received up to 6 cycles of induction therapy may receive up to 2 cycles of consolidation therapy in the absence of disease progression or unacceptable toxicity.

SUPPORTIVE CARE: Patients also receive acetaminophen orally (PO) or ibuprofen PO every 8 hours for 48 hours, diphenhydramine or equivalent IV or PO every 8 hours for 48 hours, ranitidine or equivalent IV every 8 hours for 48 hours, and dexamethasone IV up to 30 minutes prior to dosing and then at 12 hours after dosing on week 1 days 1 and 7.

After completion of study treatment, patients are followed up at 30 days, then every 3 months for 1 year.

Being tested
Acetaminophen, Dexamethasone, Diphenhydramine, Flotetuzumab, Ibuprofen
Medical subject headings
Burkitt Lymphoma, Blastic Plasmacytoid Dendritic Cell Neoplasm, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Hairy Cell, Hematologic Neoplasms, Hodgkin Disease, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Mastocytosis, Systemic

What participants receive

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

  • AcetaminophenDrug

    Also called APAP, Paracetamol, Tylenol

    Given PO

  • DexamethasoneDrug

    Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex

    Given IV

  • DiphenhydramineDrug

    Also called FAR 90X2, PM 255, Probedryl, Rigidyl

    Given IV or PO

  • 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

  • IbuprofenDrug

    Also called (.+ -.)-p-Isobutylhydratropic acid, Advil, Motrin, p-Isobutylhydratropic acid

    Given PO

  • RanitidineDrug

    Given IV

Study groups in NCT04681105
Study groupRoleWhat they receive
Treatment (flotetuzumab)ExperimentalINDUCTION THERAPY: Patients receive flotetuzumab via continuous IV infusion on days 1-28. Patients who achieve SD/PR (Cohort A) or PR/CI (Cohort B), receive an additional induction cycle. Patients who achieve PR (Cohort A) or PR/CI/MMR (Cohort B) after cycle 2 re-induction, may continue induction therapy for up to 4 more cycles. CONSOLIDATION THERAPY: Patients who achieve CR/CRi/CRh/MLFS (Cohort A) or CR/MR (Cohort B) after cycle 1 or cycle 2 of induction therapy, receive flotetuzumab via continuous IV infusion on days 1-28 for up to 5 and 6 cycles, respectively, in the absence of disease progression or unacceptable toxicity. Patients with PR (Cohort A) or PR/CI/MMR (Cohort B) who have received up to 6 cycles of induction therapy may receive up to 2 cycles of consolidation therapy in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Acetaminophen; Drug: Dexamethasone; Drug: Diphenhydramine; Biological: Flotetuzumab; Drug: Ibuprofen; Drug: Ranitidine

What is being measured

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

  1. Incidence of adverse events

    Toxicity will be graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events version 5.0 except infusion-related reaction (IRR)/cytokine release syndrome (CRS) which will be by the modified criteria proposed by Lee et al. Safety and toxicity will be assessed for each cohort independently. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, attribution, time of onset, duration, probable association with the study treatment and reversibility or outcome.

    Measured: Up to 30 days post-treatment

Secondary outcomes (5)

  1. Best response of complete remission attained

    Rates and 95% Clopper Pearson binomial confidence interval (CI) will be calculated for complete remission/response rate (confirmed complete remission [CR]/ complete remission with incomplete count recovery [CRi]/ complete remission with partial hematological recovery [CRh] [Cohort A] or CR/molecular response [MR] [Cohort B]). Remission rates will also be explored based on number/type of prior therapy(ies), the presence of extramedullary disease at the time of starting therapy, disease burden, and CD123 expression intensity.

    Measured: by the end of induction/re-induction cycles (each cycle is 28 days, up to 6 cycles)

  2. Minimal residual disease

    Assessed by multi-color flow cytometry in ALL the cohorts.

    Measured: Up to 1 year

  3. Duration of remission

    Will be estimated using the product-limit method of Kaplan and Meier.

    Measured: Up to 1 year

  4. Number/percent who bridge to allogeneic hematopoietic cell transplantation (HCT)

    Number/percent of patients who proceed to hematopoietic cell transplantation after achieving complete response/ complete remission

    Measured: Up to 1 year

  5. Overall survival

    Will be estimated using the product-limit method of Kaplan and Meier.

    Measured: Up to 1 year

Timeline

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

  1. First posted23 Dec 2020
  2. Study start18 Nov 2020
  3. Primary completion5 Aug 2025
  4. Study completion5 Aug 2025

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
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04681105
Sponsor's protocol ID
20472
Other IDs
NCI-2020-08118, 20472, P30CA033572
Status last verified
Jan 2026
First submitted
1 Dec 2020
Last updated
28 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.

    PubMed 35622074

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Acetaminophen, Dexamethasone and Diphenhydramine in people with Recurrent Acute Leukemia and Recurrent B Acute Lymphoblastic Leukemia, run by City of Hope Medical Center at 1 site 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 36 inclusion and 19 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: finished, as of the sponsor's last update on 28 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence of adverse events (time frame: Up to 30 days post-treatment). 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 NCT04681105, 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 28 Jan 2026.

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