Atypical Teratoid/Rhabdoid TumorPhase 1/2NCT06465199
Eflornithine (DFMO) and AMXT 1501 for Neuroblastoma, CNS Tumors, and Sarcomas
A Phase 1/2 study testing Eflornithine (DFMO) and AMXT 1501 Dicaprate in people with Atypical Teratoid/Rhabdoid Tumor and Embryonal Tumor With Multilayered Rosettes, run by Milton S. Hershey Medical Center at 14 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 26 years
- Conditions the study is for
- Atypical Teratoid/Rhabdoid Tumor, Embryonal Tumor With Multilayered Rosettes, Ewing Sarcoma
- What is being tested?
- Eflornithine (DFMO) and AMXT 1501 Dicaprate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 265 participants
- Where
- 14 sitesUnited States
- Study dates
- 13 May 2026to May 2035
- Phase
- Phase 1/2
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 Up to 26 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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.
- 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 participants may have active disease or no active disease.
- NB participants 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 participants 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.
- Participants must not have disease in any organs (including lungs, liver, or brain).
- Relapsed or refractory ETMR/ATRT Participants 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 participants 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 participants 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.
- Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) Participants with DIPG to start greater than 30 days, and no longer than 60 days, after standard of care radiation therapy.
- Participants 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. Participants with metastatic disease are not eligible. Participants with a biopsy and no evidence of H3K27m mutations are eligible as long as they meet radiographic criteria. Participants with H3K27m altered DMG outside of the brainstem are not eligible. Participants with progression or recurrence after initial standard of care radiation are ineligible.
- Relapsed or refractory Ewing sarcoma and osteosarcoma Participants 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 Participants 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 Participants 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.
- Participants must be able to swallow capsules.
- Participants 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.
- Participants must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy and be within the following timelines:
- Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
- 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.
- 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.
- XRT: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site.
- Note: Participants with DIPG will be required to have had up front standard of care radiation. As above, participants with DIPG must be between 30-60 days post initial up- front radiation therapy.
- Stem Cell Transplant:
- Allogeneic: No evidence of active graft vs. host disease
- Allo/Auto: ≥ 45 days must have elapsed since transplant.
- MIBG Therapy: At least 6 weeks since treatment with MIBG therapy.
- Participants must have a Lansky or Karnofsky Performance Scale score of >/= 60
- Participants 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 participants must have:
- Normal serum Cardiac Troponin Concentration
- Normal BNP (B-type natriuretic peptide) Level
- A QTcF ≤ 470 msec (or EKG with no significant findings)
- Normal ECHO defined as:
- Shortening fraction of ≥ 27% by echocardiogram, or ii. Ejection fraction of ≥ 50% by echocardiogram or radionuclide angiogram
- Renal: Participants must have adequate renal function defined as:
- For participants < 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
- For participants ≥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)
- Participants of childbearing potential must have a negative pregnancy test. Participants of childbearing potential must agree to use an effective birth control method. Participants who are lactating must agree to stop breast-feeding.
- Written informed consent in accordance with institutional and FDA guidelines must be obtained from all participants (or participants' legal representative).
Who cannot join
- 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.
Trial locations and contacts
14 sites in 1 country. Contact the study team or a site near you to ask about taking part.
14 sites in 1 country
United States14 sites, 14 recruiting
- Recruiting
University of Alabama/Children's of Alabama
Birmingham, Alabama, 35233
Bridget Tate, btate@peds.uab.edu
Elizabeth Alva
- Recruiting
Children's Medical Center
Dallas, Texas, 75235
Rachel Nam, rachel.nam@childrens.com
Tanya Watt
- Recruiting
University of Florida
Gainesville, Florida, 32611
Ashley Bayne, abayne@UFL.EDU
Joanne Lagmay
- Recruiting
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Kellie Florance, kellie.florance@hmhn.org
Derek Hanson
- Recruiting
Connecticut Children's Hospital
Hartford, Connecticut, 06106
Adam Barselau, abarselau@connecticutchildrens.org
Michael Isakoff
- Recruiting
Penn State Milton S. Hershey Medical Center and Children's Hospital
Hershey, Pennsylvania, 17033
Penn State Clinical Trials Group Email, ExtractClinicalTrials@pennstatehealth.psu.edu
Valerie Brown
- Recruiting
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96813
Andrea Siu, andrea.siu@kapiolani.org
Kelley Hutchins
- Recruiting
Children's Mercy Hospitals and Clinics
Kansas City, Kansas, 64108
Nicole Harvey, ndharvey@cmh.edu
Kevin Ginn
- Recruiting
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
Susan Hall, hallsf@archildrens.org
Kevin Bielamowicz
- Recruiting
Nicklaus Children's Hospital
Miami, Florida, 33155
Aixa Guadarrama, Aixa.Guadarrama@Nicklaushealth.org
Guillermo De Angulo
- Recruiting
Monroe Carrell Jr. Children's Hospital at Vanderbilt
Nashville, Tennessee, 37232
Aida Constantinescu, aida.constantinescu@vumc.org
Daniel Benedetti
- Recruiting
Arnold Palmer Hospital for Children
Orlando, Florida, 32806
Marie Frankos, marie.frankos@orlandohealth.com
Jamie Libes-Bander
- Recruiting
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104
Gina Martin, gina.martin@health.slu.edu
William Ferguson
- Recruiting
St. Joseph's Children's Hospital
Tampa, Florida, 33614
Jennifer Manns, jennifer.manns@baycare.org
Don Eslin
About this study
Official title: A Phase I/II Study Using Eflornithine (DFMO) and AMXT 1501 for Relapsed and Refractory Neuroblastoma, CNS Tumors, and Sarcomas
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
- Being tested
- Eflornithine (DFMO), AMXT 1501 Dicaprate
- Keywords
- DFMO
- Medical subject headings
- Rhabdoid Tumor, Neuroectodermal Tumors, Primitive, Sarcoma, Ewing, Diffuse Intrinsic Pontine Glioma, Osteosarcoma, Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eflornithine (DFMO)Drug
Also called Difluoromethylornithine
Oral DFMO capsules
AMXT 1501 DicaprateDrug
Capsule
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Eflornithine (DFMO) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Measured: 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):
- 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)
Measured: 2 years plus 5 years follow up
Secondary outcomes (5)
Phase I- Number of participants with progression free survival (PFS) during study
To evaluate the activity of AMXT 1501 in combination with DFMO based on Progression free survival (PFS)
Measured: 2 years plus 5 years follow up
Phase I- Determine the Overall Response Rate (ORR) of Participants using INSS Response
To evaluate the activity of AMXT 1501 in combination with DFMO based on Overall response rate (ORR)
Measured: 2 years
Phase II- Determine the Overall Response Rate (ORR) of Participants using INSS Response
To evaluate the efficacy of eflornithine (DFMO) in combination with AMXT 1501 (Cohort 2-4) and in a randomized arm compared to DFMO alone in neuroblastoma (Cohort 1), based upon overall response rate (ORR).
Measured: 2 years
Phase II- Length of time that participants experience Overall Survival (OS)
To evaluate the efficacy of eflornithine (DFMO) in combination with AMXT 1501 (Cohort 2-4) and in a randomized arm compared to DFMO alone in neuroblastoma (Cohort 1), based upon overall Survival (OS).
Measured: 2 years plus 5 years follow up
Phase II-Number of Participants with Adverse Events as a Measure of Safety and Tolerability
To evaluate the safety and tolerability profile of eflornithine (DFMO) in combination with AMXT 1501 in pediatric and young adult participants.
Measured: 2 years plus 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2024
- Study start13 May 2026
- Primary completionMay 2033 (estimated)
- Study completionMay 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atypical Teratoid/Rhabdoid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 265 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Aminex Therapeutics, Inc., Penn State University
- Responsible party
- Principal investigator, Giselle Sholler, Milton S. Hershey Medical Center
- Investigators
- Giselle Saulnier Sholler, MD, Study chair, Penn State Health Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06465199
- Sponsor's protocol ID
- BCC020
- Status last verified
- Sep 2026
- First submitted
- 13 Jun 2024
- Last updated
- 3 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No