Flotetuzumab for the Treatment of Pediatric Recurrent or Refractory Acute Myeloid Leukemia

NCT04158739 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 3 other identifiers: PEPN1812NCI-2019-06780UM1CA228823
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 19

Brief Summary

This phase I trial studies the side effects, best dose of flotetuzumab and how well it works in treating patients with acute myeloid leukemia (AML) that has come back (recurrent) or has not responded to treatment (refractory). This study also determines the safest dose of flotetuzumab to use in children with AML. As an immunotherapy, flotetuzumab may also cause changes in the body's normal immune system, which are also under study in this trial.

Conditions

Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicities Due to Flotetuzumab

  Number and percentage of patients experiencing dose limiting toxicities during cycle 1 that are possibly, probably, or definitely due to flotetuzumab by dose level and study part.

  Up to 29 days

• Maximum Tolerated Dose or Recommended Phase 2 Dose of Flotetuzumab

  Estimated maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of Flotetuzumab defined by the maximum dose at which fewer than one-third of toxicity-evaluable participants experience a DLT. RP2D was established by study committee based off the toxicity profile of DL1 (500 ng/kg/day).

  Up to 29 days

Secondary Outcomes (2)

• Maximum Concentration (C Max)

  Up to 9 days

• Antitumor Activity of Flotetuzumab

  Up to 2 years

Other Outcomes (2)

• Change in T-lymphocyte Population Numbers

  Up to 180 days

• CD123 Surface Expression

  Baseline

Study Arms (1)

Treatment (cytarabine, flotetuzumab)

EXPERIMENTAL

Patients receive cytarabine IT on days -6 to 0 prior to cycle 1. Patients may receive additional doses of cytarabine on day 1 of subsequent cycles per physician discretion. Patients also receive flotetuzumab IV continuously for 28 days. Treatment repeats every 29 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Cytarabine; Biological: Flotetuzumab

Interventions

Cytarabine DRUG

Given IT

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (cytarabine, flotetuzumab)

Flotetuzumab BIOLOGICAL

Given IV

Also known as: CD123 x CD3 DART Bi-Specific Antibody MGD006, CD123 x CD3 Dual Affinity Re-Targeting Bi-Specific Antibody MGD006, MGD006, RES234, S80880

Treatment (cytarabine, flotetuzumab)

Eligibility Criteria

• Age: Up to 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must weigh \>/= 17 kg
• Weight limit is due to constraints related to the concentration of the current drug formulation. If a new formulation of flotetuzumab becomes available to allow dosing of smaller patients, the protocol will be amended.
• Patients with recurrent or refractory AML are eligible. Patients must have histologic verification of malignancy at relapse.
• Patients with leukemia must have \>/= M2 marrow by morphology and/or flow cytometry and one of the following:
• Second or greater relapse
• Refractory after 2 or more chemotherapy cycles
• First relapse after primary chemotherapy-refractory disease
• First relapse after hematopoietic stem cell transplantation (HSCT)
• Central nervous system (CNS) disease:
• Patients must have the status of CNS1 and no clinical signs or neurologic symptoms suggestive of CNS leukemia, such as cranial palsy.
• Patients with CNS3 or CNS2 status may receive antecedent intrathecal chemotherapy to achieve CNS1 status prior to study entry.
• Patients with a history of CNS chloromatous disease are required to have no radiographic evidence of disease prior to enrollment.
• Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =/\< 16 years of age. Use appropriate score for study population. NOTE: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately.

You may not qualify if:

• Pregnant or breast-feeding women will not be entered on this study because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy and for 12 weeks after flotetuzumab discontinuation.
• Patients must be off steroids (unless physiologic replacement dosing) for at least 7 days prior to enrollment. If used to modify immune adverse events related to prior therapy, \>/= 14 days must have elapsed since last dose of corticosteroid.
• Patients who are currently receiving another investigational drug are not eligible.
• Patients who are currently receiving other anti-cancer agents are not eligible (except hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy).
• Patients who are receiving cyclosporine, tacrolimus or other agents to treat graft-versus-host disease post bone marrow transplant are not eligible for this trial.
• Patient has French-American-British classification (FAB) type M3 leukemia (acute promyelocytic leukemia) or identification of t(15;17).
• Patient has isolated CNS involvement or isolated extramedullary relapse.
• Patient with known human immunodeficiency virus (HIV) infection are eligible if he or she has a negative HIV serology and an undetectable viral load.
• Patient known to have one of the following concomitant genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome or any other known bone marrow failure syndrome. Patients with Down syndrome are eligible for the study.
• Patients must not weigh \< 17 kg.
• Patients must not have received prior therapy with a CD123 directed antibody or CD123 directed chimeric antigen receptor (CAR) T cells.
• Patients who have an uncontrolled infection are not eligible.
• Patients who have received a prior solid organ transplantation are not eligible.
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
• Known hypersensitivity to murine, yeast, or recombinant proteins; polysorbate 80; recombinant human serum albumin; benzyl alcohol; or any excipient contained in the flotetuzumab drug formulation. Additionally, those patients who have had a hypersensitivity reaction to etoposide that is considered likely related to polysorbate 80 are not eligible.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (19)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cytarabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

626-447-0064

Study Officials

• Adam J Lamble

  Pediatric Early Phase Clinical Trial Network

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: October 15, 2019
• First Posted: November 12, 2019
• Study Start: January 22, 2020
• Primary Completion: September 30, 2022
• Study Completion: March 31, 2026
• Last Updated: January 23, 2026
• Results First Posted: December 11, 2023

Record last verified: 2026-01

Locations

US (19)