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Refractory Solid TumorsPhase 1/2PEEL-224NCT06721689

PEEL-224, Vincristine and Temozolomide in Pediatric Solid Tumors

A Phase 1/2 study testing PEEL-224, Vincristine and Temozolomide (TMZ) in people with Refractory Solid Tumors and Relapsed Solid Tumors, run by Theodore Laetsch at 7 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The phase 1 primary objective is to determine the pediatric recommended phase 2 dose (RP2D) of PEEL-224 as a single agent (phase 1A) and in combination with vincristine and temozolomide (phase 1B). Read more about this study

Who is it for?
Ages 1 year to 30 years
What is being tested?
PEEL-224, Vincristine and Temozolomide (TMZ)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
59 participants
Where
7 sitesUnited States
Study dates
23 Mar 2025to Apr 2031
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 1 year to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Age:
  • Phase 1: Age greater than or equal to 1 year and less than or equal to18 years
  • Phase 2 Neuroblastoma (NBL) cohort: Age greater than or equal to 1 year and less than or equal to 30 years
  • Phase 2 Rhabdomyosarcoma (RMS) cohort: Age greater than or equal to 1 year and less than or equal to18 years
  • Diagnosis of:
  • Phase 1: Refractory, progressive or relapsed non-central nervous system (CNS) solid tumors who have received at least 1 line of upfront therapy. Patients must have had histologic verification of their malignancy at original diagnosis or relapse
Show all 50Show fewer
  • Phase 2: Refractory, progressive or relapsed neuroblastoma (NBL) or rhabdomyosarcoma (RMS) who have received at least 1 line of upfront therapy. Patients must have had histologic verification of their malignancy at original diagnosis or relapse.
  • Disease status:
  • Phase 1: evaluable or measurable disease
  • Phase 2, subjects with Neuroblastoma (NBL): evaluable or measurable disease by International Neuroblastoma Response Criteria (INRC); subjects with only bone marrow disease are not eligible
  • Phase 2, subjects with rhabdomyosarcoma (RMS): measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST)1.1.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 (age greater than 16 years) or Lansky Performance Status of at least 60 (age less than 16 years).
  • Females of childbearing potential must have a negative urine/serum pregnancy test.
  • Adequate bone marrow function
  • Hematologic requirements for all subjects on phase 1 and subjects on phase 2 without malignant infiltration of the bone marrow:
  • Absolute neutrophil count (ANC) greater than or equal to 750/mm3 (greater than or equal to 7 days since last dose of short acting myeloid growth factor medications (e.g. filgrastim) and greater than or equal to 14 days since last dose of long-acting myeloid medications (e.g. peg-filgrastim)
  • Platelet count ≥ 75,000 mm3 (greater than or equal to 14 days since last dose of thrombopoietin receptor agonist such as romiplostim and without platelet transfusion within previous 7 days)
  • Not refractory to packed red blood cell transfusions
  • Hematologic requirements for subjects on phase 2 with malignant infiltration of the bone marrow:
  • Absolute neutrophil count (ANC) greater than or equal to 500/mm3 (greater than or equal to 7 days since last dose of short acting myeloid growth factor medications (e.g. filgrastim) and greater than or equal to 14 days since last dose of long-acting myeloid medications (e.g. peg-filgrastim))
  • Platelet count greater than or equal to 50,000/mm3 (greater than or equal to 14 days since last dose of thrombopoietin receptor agonist such as romiplostim and without platelet transfusion within previous 7 days)
  • Not refractory to packed red blood cell transfusions
  • Patients on phase 2 with malignant infiltration of the bone marrow will not be evaluable for hematologic toxicity.
  • Adequate renal function as evidenced by creatinine clearance as calculated by the Schwartz equation (see below), radioisotope glomerular filtration rate (GFR) greater than or equal to 70 mL/min/1.73 m2, or maximum serum creatinine as below:
  • Age Maximum Serum Creatinine (mg/dL)
  • Male Female 1 to less than 2 years 0.6 0.6 2 to less than 6 years 0.8 0.8 6 to less than 10 years 1 1 10 to less than 13 years 1.2 1.2 13 to less than 16 years 1.5 1.4 greater than 16 years 1.7 1.4 Threshold derived from the Schwartz formula for estimating glomerular filtration rate (GFR) (Schwartz et al., J.Peds, 106:522,1985) utilizing child length and stature data published by the CDC The Schwartz equation for subjects less than 18 years of age: eGFR (mL/min/1.73 m2) = 0.413 x [height (cm)/serum creatinine (mg/dL)]
  • Adequate liver function
  • Aspartate Aminotransferase (AST/SGOT): less than or equal to 3 times the upper limit of normal (ULN) or less than or equal to 5 the upper limit of normal if attributable to disease involvement. For the purpose of this study, the upper limit of normal (ULN) for Aspartate Aminotransferase (AST) is 50 U/L.
  • Alanine Aminotransferase (ALT/SGPT): less than or equal to 3 times the ULN or less than or equal to 5 the upper limit of normal if attributable to disease involvement. For the purpose of this study, the upper limit of normal (ULN) for Alanine Aminotransferase (ALT) is 45 U/L.
  • Total bilirubin: less than or equal to 1.5 times the upper limit of normal with the exception of patients with Gilbert's syndrome who must have bilirubin less than 3X institutional upper limit of normal (ULN).
  • Prior Therapy: Patients must have had resolution of acute toxic effects of prior therapy to grade less than or equal to 1 according to the National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v 5.0 except organ function as noted above, adverse events (AE) that are considered clinically non-significant (i.e. alopecia), or controlled on supportive care (i.e. nausea/vomiting, hypothyroidism). Patients must meet the following minimum washout periods prior to enrollment:
  • Myelosuppressive chemotherapy: At least 14 days after the last dose of myelosuppressive chemotherapy
  • Small molecule targeted therapy: At least 7 days following the last dose of a small molecule targeted agent.
  • Antibody therapy: At least 21 days following the last dose of antibody including anti-GD2 monoclonal antibody.
  • Cellular therapy: At least 42 days following completion of a cellular therapy agent (e.g. modified T cells, NK cells, dendritic cells)
  • Autologous hematopoietic stem cell transplant and stem cell boost: Subjects must be at least 60 days from day 0 of an autologous stem cell transplant or stem cell boost.
  • Myeloid growth factors: At least 7 days following short-acting myeloid growth factor (e.g. filgrastim) and at least 14 days following the last dose of long-acting myeloid growth factor (e.g. peg-filgrastim)
  • Thrombopoietin receptor agonists: At least 14 days following last dose of thrombopoietin receptor agonist such as romiplostim
  • Interleukins, interferons, and cytokines (other than hematopoietic growth factors): At least 21 days following the completion of interleukins, interferon, or cytokines, including IL-2
  • Radiotherapy:
  • At least 14 days after limited field radiation therapy;
  • At least 90 days after total body irradiation, craniospinal radiotherapy; or radiation to greater than 50% of pelvis;
  • At least 42 days must have elapsed if other substantial BM radiation.
  • Radiopharmaceutical therapy (e.g. radiolabeled antibody, 131I- MIBG): At least 42 days after radiopharmaceutical therapy
  • Major Surgery: At least 2 weeks from prior major surgical procedure. Note: Biopsy, CNS shunt placement/revision, and central line placement/removal are not considered major.
  • Strong CYP1A2 and/or CYP3A4 inhibitors and/or inducers: At least 14 days following use of a strong CYP1A2 and/or CYP3A4 inhibitor and/or inducer. See Appendix 1 for examples. (Note that levofloxacin is permitted when clinically indicated)
  • Prior treatment with irinotecan and/or temozolomide is permitted.
  • Female patients of reproductive potential must agree to use a highly effective contraceptive method for the duration of study therapy and for at least six months after the final dose of PEEL-224. Males of reproductive potential with a female partner of child-bearing potential must use a highly effective for the duration of the study and for at least six months after the final dose of PEEL-224.
  • Subjects must agree to use sun protective measures while receiving treatment and for 4 weeks after the last dose of PEEL-224
  • Parental/guardian permission (informed consent) and if appropriate, child assent.

Who cannot join

  • Prior treatment with PEEL-224.
  • Subjects receiving any other anti-cancer agents.
  • Subjects with primary central nervous system (CNS) solid tumors or central nervous system (CNS) metastatic disease.
  • Subjects with prior allogeneic stem cell or solid organ transplantation.
  • Pregnant or lactating females.
  • Subjects with a known history of human immunodeficiency virus (HIV), hepatitis B, and/or hepatitis C (testing not required as part of screening).
  • Subjects with symptomatic congestive heart failure.

Trial locations and contacts

7 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Meghan Donnelly, MPH contact

267-426-9343

donnellymt@chop.edu

James Robinson, MSW, MPH contact

215-590-2053

robinsonj9@chop.edu

7 sites in 1 country

United States7 sites, 7 recruiting

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

    David Shulman, MD

    Recruiting

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

    David Shulman, MD

    Recruiting

  • Texas Children's Hospital

    Houston, Texas, 77030

    Jennifer Foster, MD

    Recruiting

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

    Leo Mascarhenhas, MD

    Recruiting

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

    Meghan Donnelly, MPH, 267-426-9343, donnellymt@chop.edu

    Jacquelyn Crane, MD

    Recruiting

  • University of Utah Hospital

    Salt Lake City, Utah, 84132

    Matthew Dietz, MD

    Recruiting

  • University of California, San Francisco

    San Francisco, California, 94143

    Jennifer Michlitsch, MD

    Recruiting

Other trials in United States

About this study

Official title: A Phase 1/2 Clinical Trial of the Novel Topoisomerase I Inhibitor PEEL-224 as a Single Agent and in Combination With Vincristine and Temozolomide in Children With Refractory, Progressive or Relapsed Solid Tumors

The phase 1 primary objective is to determine the pediatric recommended phase 2 dose (RP2D) of PEEL-224 as a single agent (phase 1A) and in combination with vincristine and temozolomide (phase 1B). The phase 2 primary objective is to estimate the objective response rate (ORR) in children with refractory, progressive and relapsed NBL and rhabdomyosarcoma (RMS) treated with the RP2D of PEEL-224 in combination with vincristine and temozolomide.

Read the detailed description

PEEL-224 will be a multi-institutional study conducted at pediatric cancer centers. Phase 1 will enroll approximately 24 subjects (maximum of 12 evaluable subjects in phase 1A and 12 evaluable subjects in phase 1B) between ages 1 to 18 years of age with a refractory, progressive or relapsed solid tumor. Phase 2 will enroll a maximum of 18 evaluable subjects with refractory, progressive or relapsed NBL and a maximum of 17 evaluable subjects with refractory, progressive or relapsed RMS. PEEL-224 will be administered at the assigned dose on days 1 and 8 of 21-day cycles as a single agent (phase 1A) or in combination with vincristine on days 1 and 8 and temozolomide on days 1-5 (phase 1B and phase 2). Subjects may continue protocol therapy for up to 24 cycles (approximately 18 months) in the absence of progressive disease or unacceptable toxicity. Subjects will be monitored with physical exams and labs on days 1 and 8 of each cycle and disease response assessments and patient reported outcome assessments will be performed after cycles 2, 4, 6, 9, 12, 18, and 24. During phase 1, PK blood samples will be drawn during cycle 1. The primary phase 1 endpoints are cycle 1 dose limiting toxicity (DLT) to define the RP2D. The primary phase 2 endpoint is best overall objective response to define the ORR.

Being tested
PEEL-224, Vincristine, Temozolomide (TMZ)
Keywords
Relapsed, Refractory, Solid Tumor
Medical subject headings
Neuroblastoma, Rhabdomyosarcoma, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PEEL-224Drug

    PEEL-224 (PEG-[SN22]4) is a novel topoisomerase I inhibitor

  • VincristineDrug

    Vincristine is an inhibitor of microtubular formation which is approved by the Food and Drug Administration (FDA) and is commercially available.

  • Temozolomide (TMZ)Drug

    Temozolomide is an alkylating agent which is approved by the FDA and is commercially available.

Study groups in NCT06721689
Study groupRoleWhat they receive
PEEL-224ExperimentalPhase 1A will test the safety, tolerability and PK profile of PEEL-224 as a single agent in pediatric patients with refractory, progressive and relapsed solid tumors.
Receives: Drug: PEEL-224
PEEL-224, Vincristine, and TemozolomideExperimentalPhase 1B will test the safety, tolerability and pharmacokinetic profile of PEEL-224 in combination with vincristine and temozolomide in pediatric subjects with refractory, progressive and relapsed solid tumors. Phase 2 will preliminary evaluate the activity profile of PEEL-224 in combination with vincristine and temozolomide in pediatric patients with refractory, progressive and relapsed NBL and RMS.
Receives: Drug: PEEL-224; Drug: Vincristine; Drug: Temozolomide (TMZ)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1A and Phase 1B: Number of participants who experience a dose limiting toxicity (DLT)

    The observation of a dose-limiting toxicity (DLT) or lack of observation of DLT in the period between treatment initiation up to initiation of cycle 2 treatment. A dose limiting toxicity (DLT) describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment.

    Measured: 1 month

  2. Phase 2 Neuroblastoma Cohort (NBL): Number of paricptants who achieve a complete response (CR), partial response (PR), or minor response (MR)

    Objective response as assessed by the Revised International Neuroblastoma Response Criteria (INRC). Response is defined as complete response (CR), partial response (PR) or minor response (MR), using best response measured at any point prior to local control.

    Measured: 2 years

  3. Phase 2 Rhabdomyosarcoma (RMS) Cohort: Number of participants who achieve a complete response (CR) or partial response (PR)

    Objective response as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Response is defined as complete response (CR) or partial response (PR), using best response measured at any point prior to local control.

    Measured: 2 years

Secondary outcomes (4)

  1. Number of subjects with an Adverse Event (AE) of greater than or equal to grade 3 at least possibly attributable to study treatment

    Adverse Events (AEs) will be graded by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Measured: 30 days after last dose

  2. Area under the plasma-concentration-time-curve of PEEL-224

    To characterize the pharmacokinetic (PK) profile of free SN22 and SN22 bound to PEG (PEEL-224)

    Measured: 1 month

  3. Number of participants demonstrating anti-tumor activity of PEEL-224

    To preliminarily evaluate antitumor activity of PEEL-224 by estimating event-free survival (EFS)

    Measured: 2 years

  4. Number of participants demonstrating anti-tumor activity of the combination of PEEL-224, vincristine and temozolomide

    To preliminarily evaluate antitumor activity of the combination of PEEL-224, vincristine and temozolomide by estimating event-free survival (EFS )

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Dec 2024
  2. Study start23 Mar 2025
  3. Primary completionApr 2030 (estimated)
  4. Study completionApr 2031 (estimated)

Resources

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
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
59 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06721689
Sponsor's protocol ID
24-022741
Acronym
PEEL-224
Status last verified
Oct 2026
First submitted
2 Dec 2024
Last updated
6 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing PEEL-224, Vincristine and Temozolomide (TMZ) in people with Refractory Solid Tumors and Relapsed Solid Tumors, run by Theodore Laetsch at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 50 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 6 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Meghan Donnelly, MPH (267-426-9343, donnellymt@chop.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1A and Phase 1B: Number of participants who experience a dose limiting toxicity (DLT) (time frame: 1 month). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06721689.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2026.

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