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

NCT ID: NCT06465199

Last Updated: 2026-02-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 289 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-02-28
• Study Completion Date: 2035-02-28

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

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I- AYA Cohort

The initial phase I will be an AYA (adolescents and young adult) cohort that will be for subjects ≥12 years of age at enrollment in a standard 3+3 design in which groups of 3 subjects per cohort will be treated and assessed. Subjects will receive up to twenty-four (24), 28-day cycles of AMXT 1501 combined with DFMO. Subjects 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.

Group Type: EXPERIMENTAL

Eflornithine (DFMO)

Intervention Type: DRUG

Oral DFMO capsules

AMXT 1501 Dicaprate

Intervention Type: DRUG

Capsule

Phase I- Pediatric Cohort

The second phase I will be a pediatric cohort that will be for subjects \< 12 years of age at enrollment in a standard 3+3 design in which groups of 3 subjects per cohort will be treated and assessed. Subjects will receive up to twenty-four (24), 28-day cycles of AMXT 1501 combined with DFMO. Subjects 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.

Group Type: EXPERIMENTAL

Eflornithine (DFMO)

Intervention Type: DRUG

Oral DFMO capsules

AMXT 1501 Dicaprate

Intervention Type: DRUG

Capsule

Phase II- Arm A: AMXT 1501 + DFMO

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. Subjects 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.

Subjects in cohort 1 who progress on DFMO alone (and have met the primary PFS endpoint) may cross over to AMXT 1501+DFMO.

Group Type: EXPERIMENTAL

Eflornithine (DFMO)

Intervention Type: DRUG

Oral DFMO capsules

AMXT 1501 Dicaprate

Intervention Type: DRUG

Capsule

Phase II- Arm B: DFMO Alone

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. Subjects 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.

Subjects in cohort 1 who progress on DFMO alone (and have met the primary PFS endpoint) may cross over to AMXT 1501+DFMO.

Group Type: ACTIVE_COMPARATOR

Eflornithine (DFMO)

Intervention Type: DRUG

Oral DFMO capsules

Interventions

Eflornithine (DFMO)

Oral DFMO capsules

Intervention Type: DRUG

AMXT 1501 Dicaprate

Capsule

Intervention Type: DRUG

Other Intervention Names

Difluoromethylornithine

Eligibility Criteria

Inclusion Criteria

1. Age:

All subjects: Must be a maximum of 21 years of age at diagnosis

Age at enrollment by Phase:

1. Phase I-AYA (adolescents and young adult) Cohort: ≥12 years of age at enrollment.

2. Phase I-Pediatric Cohort: < 12 years of age at enrollment; may start only after DSMB review confirms the RP2D from the AYA cohort. No subject < 12 years will be treated at a dose level higher than the RP2D established in the Phase I-AYA Cohort.

3. Phase II: ≤ 21 years of age at diagnosis (with possibly two different age-specific RP2Ds).

2. Pathology

All subjects 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)

3. Tumor assessment:

Disease staging must be performed at baseline during the 28 day screening period prior to first dose of study drug.

4. Disease Status:

Relapsed or Refractory Neuroblastoma Relapsed disease defined as: High-risk neuroblastoma that was previously in remission after standard therapy (at least 4 cycles of aggressive multi-drug induction chemotherapy, with or without radiation, surgery, and immunotherapy, or according to a standard high-risk treatment/neuroblastoma protocol).

Refractory disease defined as: High-risk neuroblastoma that 1) failed to achieve CR after at least 4 cycles of aggressive multi-drug induction chemotherapy with or without radiation and surgery, followed by immunotherapy, or according to a standard high-risk treatment/neuroblastoma protocol, or 2) progression during upfront therapy or 3) with disease remaining after standard immunotherapy.

Eligible NB subjects may have active disease or no active disease.

NB Subjects with no active disease need to meet the following criteria:

Timing from prior therapy: Enrollment (first dose of study drug) no later than 60 days from most recent therapy.

NB Subjects with active disease need to meet the following criteria:

• Received at least one recent treatment for their relapse/refractory disease and is stable (SD) or better on this treatment.

*Stable disease defined as non-progression over 2 separate imaging studies at least 6 weeks apart

• Subjects must not have disease in any organs (including lungs, liver, or brain).
• Measurable tumor size is < 2 cm
• Bone marrow < 40% involvement

Relapsed or refractory ETMR/ATRT Subjects that have relapsed following standard of care therapy or having progressed during standard of care therapy and non-responsive/progressive to accepted curative therapy, including up-front chemotherapy and radiation and/or high-dose chemotherapy with stem cell rescue.

ETMR/ATRT Subjects with no active disease need to meet the following criteria:

Timing from prior therapy: Enrollment (first dose of study drug) no later than 60 days from most recent therapy.

ETMR/ATRT Subjects with active disease need to meet the following criteria:

• Received at least one recent treatment for their relapse/refractory disease and is stable (SD) or better on this treatment.

*Stable disease defined as non-progression over 2 separate imaging studies at least 6 weeks apart

Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) Subjects with DIPG to start greater than 30 days, and no longer than 60 days, after standard of care radiation therapy.

Subjects with newly-diagnosed typical DIPG, defined as tumors with a pontine epicenter and diffuse involvement of the pons on at least 1 axial T2-weighted image, are eligible. No histologic confirmation is required. Subjects with metastatic disease are not eligible. Subjects with a biopsy and no evidence of H3K27m mutations are eligible as long as they meet radiographic criteria. Subjects with H3K27m altered DMG outside of the brainstem are not eligible. Subjects with progression or recurrence after initial standard of care radiation are ineligible.

Relapsed or refractory Ewing sarcoma and osteosarcoma Subjects that have relapsed following standard of care therapy or having progressed during standard of care therapy. Standard of care therapy for Ewing sarcoma and osteosarcoma includes multi-agent chemotherapy with local control consisting of either surgery or radiation therapy.

EWS/OST Subjects with no active disease need to meet the following criteria:

Timing from prior therapy: Enrollment (first dose of study drug) no later than 60 days from most recent therapy.

EWS/OST Subjects with active disease need to meet the following criteria:

• Received at least one recent treatment for their relapse/refractory disease and is stable (SD) or better on this treatment.

*Stable disease defined as non-progression over 2 separate imaging studies at least 6 weeks apart

5. Subjects must be able to swallow capsules.

6. Subjects with CNS disease currently taking steroids must have been on a stable dose of steroids for at least one week and must not have progressive hydrocephalus at enrollment.

7. Subjects must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy and be within the following timelines:

1. Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea).

2. Small Molecule Inhibitor (anti-neoplastic agent): At least 7 days since the completion of therapy with a small molecule inhibitor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the Study Chair.

3. Immunotherapy: At least 4 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines, CAR-T cells except for anti-GD2 Monoclonal antibodies (ex. naxitamab, dinutuximab, etc.) which should be at least 2 weeks since prior treatment with a monoclonal antibody.

4. XRT: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site.

Note: Subjects with DIPG will be required to have had up front standard of care radiation. As above, subjects with DIPG must be between 30-60 days post initial up front radiation therapy.

5. Stem Cell Transplant:

1. Allogeneic: No evidence of active graft vs. host disease

2. Allo/Auto: ≥ 45 days must have elapsed since transplant.

6. MIBG Therapy: At least 6 weeks since treatment with MIBG therapy.

8. Subjects must have a Lansky or Karnofsky Performance Scale score of >/= 60

9. Subjects must have adequate organ function at the time of enrollment:

• Hematological: Hematological recovery as defined by ANC ≥750/μL (unsupported- >24 hrs off G-CSF and 7 days off neulasta)
• Liver: Adequate liver function as defined by AST and ALT <10x upper limit of normal
• Cardiac: all subjects must have:

1. Normal serum Cardiac Troponin Concentration

2. Normal BNP (B-type natriuretic peptide) Level

3. A QTcF ≤ 470 msec (or EKG with no significant findings)

4. Normal ECHO defined as:

i. Shortening fraction of ≥ 27% by echocardiogram, or ii. Ejection fraction of ≥ 50% by echocardiogram or radionuclide angiogram

• Renal: Subjects must have adequate renal function defined as:

1. For subjects < 17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Bedside Schwartz equation is: [(0.413) X (Height in cm)] / SCr

2. For subjects ≥17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Cockcroft and Gault formula is: [(140-age) x (Wt in kg) x (0.85 if female)] / (72 x SCr)

3. OR a 24 hour urine Creatinine clearance ≥ 70 mL/min/1.73 m2

10. Subjects of childbearing potential must have a negative pregnancy test. Subjects of childbearing potential must agree to use an effective birth control method. Subjects who are lactating must agree to stop breast-feeding.

11. Written informed consent in accordance with institutional and FDA guidelines must be obtained from all subjects (or subjects' legal representative).

Exclusion Criteria

1. BSA of <0.25 m2

2. Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.

3. Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from the hematological and bone marrow suppression effects of prior chemotherapy.

4. Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.

5. Subjects 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.

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aminex Therapeutics, Inc.

INDUSTRY

Sponsor Role: collaborator

Penn State University

OTHER

Sponsor Role: collaborator

Milton S. Hershey Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Giselle Sholler

Beat Childhood Cancer Chair

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Giselle Saulnier Sholler, MD

Role: STUDY_CHAIR

Penn State Health Children's Hospital

Locations

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status: RECRUITING

Connecticut Children's Hospital

Hartford, Connecticut, United States

Site Status: RECRUITING

St. Joseph's Children's Hospital

Tampa, Florida, United States

Site Status: RECRUITING

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

Hershey, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

BCC Enroll

Role: CONTACT

BCCEnroll@pennstatehealth.psu.edu

7175310003

Facility Contacts

Susan Hall

Role: primary

hallsf@archildrens.org

Adam Barselau

Role: primary

abarselau@connecticutchildrens.org

Jennifer Manns

Role: primary

jennifer.manns@baycare.org

Penn State Clinical Trials Group Email

Role: primary

ExtractClinicalTrials@pennstatehealth.psu.edu

Related Links

https://research.beatcc.org/

Beat Childhood Cancer Research Consortium website

Other Identifiers

BCC020

Identifier Type: -

Identifier Source: org_study_id