ADVL1011, A Phase 1 Study of JAK Inhibition (INCB018424) in Children with Relapsed or Refractory Solid Tumors, Leukemias, and Myeloproliferative Neoplasms
A phase I trial of INCB018424 administered orally BID on a continuous schedule will be conducted in children with refractory solid tumors, relapsed leukemias, or MPNs. Initially, the spectrum of toxicity and maximum tolerated dose (MTD) will be defined in patients with solid tumors. Patients with relapsed leukemias and MPNs (including, but not restricting to, patients with known CRLF2 and/or JAK mutations) will be entered at one dose level behind that of solid tumor patients, or at the starting dose level if dose escalation has not yet occurred in solid tumor patients. Pharmacokinetics of INCB018424 will be studied in patients with solid tumors, leukemias, and MPNs. Pharmacodynamic effects of INCB018424 on intracellular kinase signaling will be assessed by plasma inhibitory assays in all consenting patients and phosphoflow cytometry and JAK mutation sequencing and allele-specific PCR (if relevant) will also be performed in leukemia and MPN patients.
1. Patients must be > than 12 months and ≤ 21 years of age (≤ 18 years of age at this institution) at the time of study enrollment.
2. Patients must have a BSA ≥ 0.65m2 at the time of study enrollment.
3. Patients must have had histologic verification of an extracranial solid
tumor, leukemia or myeloproliferative neoplasms (MPN) at original diagnosis or relapse.
4. Patients must have either measurable or evaluable tumor.
5. Patient’s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
6. Performance Level: Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age.
7. Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
8. Patients must have adequate bone marrow, renal, and liver function.
9. All patients and/or their parent or legal guardian must sign a written informed consent.
10. All institutional, FDA, and NCI requirements for human studies must be met.