Inclusion Criteria:
1. 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.
2. 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.
- - 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.
3. 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.
4. Adequate available archival tumor tissue as described in Section 5.4.3. Tumor tissue
from the most recent biopsy or resection is preferred, if adequate sample is
available. If no archival tumor tissue is available, enrollment may be permitted
with prior approval by the overall study PI or designee.
5. 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).
6. Females of childbearing potential must have a negative urine/serum pregnancy test.
7. 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.
8. 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)]
9. 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).
10. 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)
11. Prior treatment with irinotecan and/or temozolomide is permitted.
12. 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.
13. Subjects must agree to use sun protective measures while receiving treatment and for
4 weeks after the last dose of PEEL-224. 14. Parental/guardian permission (informed consent) and if appropriate, child assent.
Exclusion Criteria:
1. Prior treatment with PEEL-224.
2. Subjects receiving any other anti-cancer agents.
3. Subjects with primary central nervous system (CNS) solid tumors or central nervous
system (CNS) metastatic disease.
4. Subjects with prior allogeneic stem cell or solid organ transplantation.
5. Pregnant or lactating females.
6. Subjects with a known history of human immunodeficiency virus (HIV), hepatitis B,
and/or hepatitis C (testing not required as part of screening).
7. Subjects with symptomatic congestive heart failure.
