A Phase II Study of Vibecotamab (XmAb14045) for MRD- Positive AML and MDS After Hypomethylating Agent Failure

NCT05285813 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2021-1124NCI-2022-02215
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II single-center study to evaluate the safety and effectiveness of vibecotamab, a CD3-CD123 bispecific antibody, in patients with acute myeloid leukemia with persistent or recurrent measurable residual disease and in patients with myelodysplastic syndrome that has not responded to or relapsed after conventional therapy

Conditions

AML; MDS

Outcome Measures

Primary Outcomes (2)

• To determine the MRD negativity rate after 4 cycles of vibecotamab in patients with AML with MRD

  through study completion, an average of 1 year

• To determine the response rate (defined as CR + marrow CR [mCR] + partial remission [PR] + hematologic improvement [HI]) after 4 cycles of vibecotamab in patients with MDS after HMA failure

  through study completion, an average of 1 year

Study Arms (2)

AML MRD cohort only

EXPERIMENTAL

Each study cycle is 28 days. Vibecotamab by vein (IV) over about 2 hours On Days 1, 3, 5, 8, 15 and 22 of Cycle 1 and then on Days 1, 8, 15 and 22 of Cycles 2-4.

Drug: Vibecotamab; Drug: Dexamethasone; Drug: Acetaminophen; Drug: Diphenhydramine

MDS post-HMA failure cohort only

EXPERIMENTAL

Each study cycle is 28 days. Vibecotamab by vein (IV) over about 2 hours On Days 1, 3, 5, 8, 15 and 22 of Cycle 1 and then on Days 1, 8, 15 and 22 of Cycles 2-4.

Drug: Vibecotamab; Drug: Dexamethasone; Drug: Acetaminophen; Drug: Diphenhydramine

Interventions

Dexamethasone DRUG

Given by vein (IV) over about 60 minutes before the dose

Also known as: Decadron

AML MRD cohort only; MDS post-HMA failure cohort only

Acetaminophen DRUG

Given by mouth (PO) about 30-60 minutes before the dose

Also known as: Tylenol®, Dorcol®, Feverallâ"¢, Panadol®, APAP, N-Acetyl-P-Aminophenol, Paracetamol, Ofirmevâ"¢

AML MRD cohort only; MDS post-HMA failure cohort only

Diphenhydramine DRUG

Given by mouth (PO) or Given by vein (IV) about 30-60 minutes before the dose

Also known as: Benadryl®

AML MRD cohort only; MDS post-HMA failure cohort only

Vibecotamab DRUG

Given by vein (IV)

Also known as: XmAb14045

AML MRD cohort only; MDS post-HMA failure cohort only

Eligibility Criteria

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

You may qualify if:

• Adults ≥18 years of age
• AML MRD cohort only: AML in first or second morphologic remission (defined as complete remission \[CR\], complete remission with incomplete hematologic recovery \[CRi\], or morphologic leukemia-free state \[MLFS\]) who have received a minimum prior therapy with at least 1 course of intensive intermediate to high-cytarabine-based chemotherapy or at least 2 courses of lower-intensity therapy (e.g. hypomethylating agent or low-dose cytarabine-based)
• AML MRD cohort only: Persistent or recurrent MRD positivity detected by MFC at a level of ≥0.1%.
• AML MRD cohort only: For patients who are MRD positive by MFC, residual leukemia must be positive for CD123 expression at a level of at least 20% (as assessed by clinical pathologist)
• MDS post-HMA failure cohort only: MDS that is intermediate, high risk or very high risk by the Revised International Prognostic Scoring System (IPSS) or CMML-1 or CMML-2 who have not responded after at least 4 cycles of azacitidine and/or decitabine or who progressed or relapsed after azacitidine and/or decitabine, regardless of the number of cycles received
• MDS post-HMA failure cohort only: Aberrant blasts must be positive for CD123 expression by MFC at a level of at least 20% (as assessed by clinical pathologist)
• Performance status 2 (ECOG Scale).
• Female patients of childbearing potential must agree to use a highly effective method of birth control during and for 4 weeks after the last dose of vibecotamab and must also refrain from oocyte donation during this time period. Women are considered to be of childbearing potential unless it is documented that they are over the age of 60 OR postmenopausal by history with no menses for 1 year and confirmed by follicle-stimulating hormone (using local reference ranges) OR have a history of hysterectomy and/or bilateral oophorectomy OR have a history of bilateral tubal ligation. Highly effective methods of birth control include hormonal birth control (oral, intravaginal, transdermal, implantable, or intrauterine), intrauterine devices, vasectomized partner, or any double-barrier methods (combination of male condom and spermicide with either cap, diaphragm, or sponge).
• Male patients and their female partner of childbearing potential must agree to use highly effective contraception, as above, and refrain from donating sperm during the treatment period and for at least 4 weeks after the last dose of vibecotamab.
• Signed informed consent

You may not qualify if:

• Prior treatment with vibecotamab or anti-CD123-directed therapy.
• Clinically significant organ dysfunction, defined as:
• AST or ALT \>3x the upper limit of normal (ULN)
• Total bilirubin \>1.5x the ULN, unless due to ongoing hemolysis or Gilbert's syndrome
• Creatinine clearance \<30 mL/min
• Active Grade III-V cardiac failure as defined by the New York Heart Association Criteria.
• Active serious infection not controlled by oral or intravenous antibiotics (e.g. persistent fever or lack of clinical improvement despite antimicrobial treatment).
• Patients who are expected to be able to proceed with stem cell transplantation within the next 30 days
• Known human immunodeficiency virus (HIV) with detectable viral load.
• Known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection Note: Patients who have isolated positive hepatitis B core antibody (ie, in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load. Patients who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load.
• Patients with a prior or concurrent malignancy whose natural history or treatment is not anticipated to interfere with the safety or efficacy assessment of the investigational regimen may be included only after discussion with the PI
• Treatment with any antileukemic agents or chemotherapy agents in the last 7 days or 5 half-lives (whichever is sooner) before study entry

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Interventions

Dexamethasone; Calcium Dobesilate; Acetaminophen; Diphenhydramine

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Ethylamines; Benzhydryl Compounds

Study Officials

• Nicholas Short, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2022
• First Posted: March 18, 2022
• Study Start: May 6, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

US (1)