Eflornithine (DFMO) and AMXT 1501 for Neuroblastoma, CNS Tumors, and Sarcomas

NCT06465199 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: BCC020
• Study Type: interventional
• Target: 289
• Locations: 1 country
• Sites: 10

Brief Summary

The purpose of this study is to evaluate the investigational oral drug AMXT 1501 in combination with oral eflornithine (DFMO). An investigational drug is one that has not been approved by the U.S. Food \& Drug Administration (FDA), or any other regulatory authorities around the world for use alone or in combination with any drug, for the condition or illness it is being used to treat. The goals of this part of the study are:

• Establish a recommended dose of AMXT 1501 in combination with DFMO
• Test the safety and tolerability of AMXT 1501 in combination with DFMO
• To determine the activity of study treatments chosen based on:
• How each subject responds to the study treatment
• How long a subject lives without their disease returning/progressing

Conditions

Osteosarcoma; Neuroblastoma; DIPG Brain Tumor; Embryonal Tumor With Multilayered Rosettes; Ewing Sarcoma; Diffuse Intrinsic Pontine Glioma; Atypical Teratoid/Rhabdoid Tumor

Keywords

DFMO

Outcome Measures

Primary Outcomes (3)

• Phase I- Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  To evaluate the safety, tolerability and recommended phase 2 dose (RP2D) of AMXT 1501 in combination with oral DFMO in pediatric and young adult participants.

  28 days

• Phase II- Number of Cohort 1 participants with progression free survival (PFS) during study

  To evaluate, in a prospective randomized clinical trial, the efficacy of eflornithine (DFMO) in combination with AMXT 1501 compared to DFMO alone in neuroblastoma (Cohort 1) based upon Progression Free Survival (PFS)

  2 years plus 5 years follow up

• Phase II- Number of Cohort 2-4 participants with progression free survival (PFS) during study

  To evaluate the efficacy of eflornithine (DFMO) in combination with AMXT 1501 in non-randomized (Cohorts 2-4) based upon Progression Free Survival (PFS): 2\. Cohort 2-Relapsed/refractory Embryonal Tumor with Multilayered Rosettes (ETMR) Atypical Teratoid Rhabdoid Tumor (ATRT) 3. Cohort 3-Diffuse Intrinsic Pontine Glioma (DIPG) at diagnosis after standard of care radiation therapy 4. Cohort 4- Relapsed/refractory Ewing Sarcoma (EWS) and Osteosarcoma (OST)

  2 years plus 5 years follow up

Secondary Outcomes (5)

• Phase I- Number of participants with progression free survival (PFS) during study

  2 years plus 5 years follow up

• Phase I- Determine the Overall Response Rate (ORR) of Participants using INSS Response

  2 years

• Phase II- Determine the Overall Response Rate (ORR) of Participants using INSS Response

  2 years

• Phase II- Length of time that participants experience Overall Survival (OS)

  2 years plus 5 years follow up

• Phase II-Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  2 years plus 30 days

Study Arms (4)

Safety Run-in

EXPERIMENTAL

This study will include a safety run-in of 6 participants. The first 3 participants will be ≥ 12 years of age. The next 3 participants will be ≥ 6 years of age. The study will then move on to the Phase I.

Drug: Eflornithine (DFMO); Drug: AMXT 1501 Dicaprate

Phase I

EXPERIMENTAL

Phase I will use a standard 3+3 design in which groups of 3 participants per dose level will be treated and assessed. Participants will receive up to twenty-four (24), 28-day cycles of AMXT 1501 combined with DFMO. Participants will receive oral AMXT 1501 at a starting dose of 350 mg/m2 BID each day. The dose escalation scheme for subsequent groups and modifications for dose limiting toxicities (DLT) are detailed in the protocol.

Drug: Eflornithine (DFMO); Drug: AMXT 1501 Dicaprate

Phase II- Arm A: AMXT 1501 + DFMO

EXPERIMENTAL

In this portion of the study, cohort 1 will be randomized to either receive Arm A: oral AMXT 1501 at the recommended phase 2 dose (RP2D) found in the Phase I along with oral DFMO at the RP2D found in the Phase I on each day of study or Arm B: oral DFMO alone at the recommended phase 2 dose (RP2D) found in the Phase I. Participants will receive up to twenty-four (24), 28-day cycles of their assigned treatment. Cohorts 2 (ETMR/ATRT), 3 (DIPG), and 4 (Sarcomas) will automatically be assigned to Arm A with AMXT 1501 in combination with DFMO. Participants in cohort 1 who progress on DFMO alone (and have met the primary PFS endpoint) may cross over to AMXT 1501+DFMO.

Drug: Eflornithine (DFMO); Drug: AMXT 1501 Dicaprate

Phase II- Arm B: DFMO Alone

ACTIVE COMPARATOR

In this portion of the study, cohort 1 will be randomized to either receive Arm A: oral AMXT 1501 at the recommended phase 2 dose (RP2D) found in the Phase I along with oral DFMO at the RP2D found in the Phase I on each day of study or Arm B: oral DFMO alone at the recommended phase 2 dose (RP2D) found in the Phase I. Participants will receive up to twenty-four (24), 28-day cycles of their assigned treatment. Cohorts 2 (ETMR/ATRT), 3 (DIPG), and 4 (Sarcomas) will automatically be assigned to Arm A with AMXT 1501 in combination with DFMO. Participants in cohort 1 who progress on DFMO alone (and have met the primary PFS endpoint) may cross over to AMXT 1501+DFMO.

Drug: Eflornithine (DFMO)

Interventions

Eflornithine (DFMO) DRUG

Oral DFMO capsules

Also known as: Difluoromethylornithine

Phase I; Phase II- Arm A: AMXT 1501 + DFMO; Phase II- Arm B: DFMO Alone; Safety Run-in

AMXT 1501 Dicaprate DRUG

Capsule

Phase I; Phase II- Arm A: AMXT 1501 + DFMO; Safety Run-in

Eligibility Criteria

• Age: Up to 26 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age:
• All participants : Must be a maximum of 26 years of age at diagnosis
• Age at enrollment by Phase:
• Safety Run-in (Dose level 1)-The first three (3) participants enrolled will be ≥ 12 years of age at enrollment. Once evaluated for safety by DSMB, we will move on to the next three (3) participants enrolled who will be ≥6 years of age at enrollment. Once evaluated for safety by DSMB, we will move on to the Phase I.
• Phase I and II: ≤ 26 years of age at diagnosis.
• Pathology
• All participants must have a confirmed pathologic diagnosis of tumor type (except for DIPG):
• Relapsed/refractory Neuroblastoma (NB)
• Relapsed/refractory Embryonal tumor with multilayer rosettes (ETMR)
• Relapsed/refractory Atypical teratoid rhabdoid tumor (ATRT)
• Newly diagnosed Diffuse Intrinsic Pontine Glioma (DIPG)- radiologic diagnosis acceptable
• Relapsed/refractory Ewing Sarcoma (EWS)
• Relapsed/refractory Osteosarcoma (OST)
• Tumor assessment:
• Disease staging must be performed at baseline during the 28 day screening period prior to first dose of study drug.

You may not qualify if:

• BSA of \<0.25 m2
• Investigational Drugs: Participants who are currently receiving another investigational drug are excluded from participation.
• Anti-cancer Agents: Participants who are currently receiving other anticancer agents are not eligible. Participants must have fully recovered from the hematological and bone marrow suppression effects of prior chemotherapy.
• Infection: Participants who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
• Participants who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.

Sponsors & Collaborators

• Penn State University: collaborator
• Milton S. Hershey Medical Center: lead
• Aminex Therapeutics, Inc.: collaborator

Study Sites (10)

University of Alabama/Children's of Alabama

Birmingham, Alabama, 35233, United States

RECRUITING

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

RECRUITING

Connecticut Children's Hospital

Hartford, Connecticut, 06106, United States

RECRUITING

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

RECRUITING

Arnold Palmer Hospital for Children

Orlando, Florida, 32806, United States

RECRUITING

St. Joseph's Children's Hospital

Tampa, Florida, 33614, United States

RECRUITING

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96813, United States

RECRUITING

Penn State Milton S. Hershey Medical Center and Children's Hospital

Hershey, Pennsylvania, 17033, United States

RECRUITING

Monroe Carrell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, 37232, United States

RECRUITING

Children's Medical Center

Dallas, Texas, 75235, United States

RECRUITING

Related Links

• Beat Childhood Cancer Research Consortium website

MeSH Terms

Conditions

Rhabdoid Tumor; Neuroectodermal Tumors, Primitive; Sarcoma, Ewing; Diffuse Intrinsic Pontine Glioma; Osteosarcoma; Neuroblastoma

Interventions

Eflornithine

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Glioma; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroectodermal Tumors, Primitive, Peripheral

Intervention Hierarchy (Ancestors)

Ornithine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino

Study Officials

• Giselle Saulnier Sholler, MD

  Penn State Health Children's Hospital

  STUDY CHAIR

Central Study Contacts

BCC Enroll

CONTACT

7175310003; BCCEnroll@pennstatehealth.psu.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Beat Childhood Cancer Chair

Study Record Dates

• First Submitted: June 13, 2024
• First Posted: June 18, 2024
• Study Start: May 13, 2026
• Primary Completion (Estimated): May 1, 2033
• Study Completion (Estimated): May 1, 2035
• Last Updated: June 12, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)