INCB18424 in Treating Young Patients With Relapsed or Refractory Solid Tumor, Leukemia, or Myeloproliferative Disease

Status: Recruiting
Phase: Phase 1
Diagnosis: Pediatric Solid Tumors, Pediatric Leukemia
NCT ID: NCT01164163 (View complete trial on
DFCI Protocol ID: 10-350


RATIONALE: INCB18424 (Ruxolitinib) may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase 1 clinical trial is studying the side effects and best dose of INCB18424 in treating young patients with relapsed or refractory solid tumor, leukemia, or myeloproliferative disease.


Conducting Institutions:
Dana-Farber Cancer Institute, Children's Hospital Boston

Overall PI:
Suzanne Shusterman, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:

Dana-Farber Cancer Institute: Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP,

Eligibility Criteria

DISEASE CHARACTERISTICS: - Histologically confirmed diagnosis of one of the following: - Extracranial solid tumor - Leukemia - At least 25% blasts in the bone marrow (M3) - Myeloproliferative neoplasm (MPN) - At original diagnosis or relapse - Current diagnostic criteria for MPNs include polycythemia vera, essential thrombocythemia, juvenile myelomonocytic leukemia, myelofibrosis, and atypical chronic myeloid leukemia - Measurable or evaluable disease (for patients with solid tumors) - Current disease state is one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life - No active CNS involvement (positive CSF cytology or known radiographic evidence of leptomeningeal dissemination) for patients with leukemia or MPNs PATIENT CHARACTERISTICS: - Karnofsky performance status (PS) 50-100% (for patients > 16 years old) or Lansky PS 50-100% (for patients ≤ 16 years old) - Patients who are unable to walk because of paralysis, but who can actively sit up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance status - Patients with solid tumors* must meet the following criteria: - Peripheral ANC ≥ 1,000/mm^3 - Platelet count ≥ 100,000/mm^3 (transfusion-independent, defined as > 7 days since prior platelet transfusions) - Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions) - ALT ≤ 110 U/L NOTE: *Patients with solid tumors and known bone marrow metastatic disease are eligible for study, but not evaluable for hematologic toxicity. These patients must not be known to be refractory to RBC or platelet transfusions. - Patients with leukemia or MPNs must meet the following criteria: - Platelet count ≥ 20,000/mm^3 (may receive platelet infusions) - Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions) - ALT ≤ 225 U/L - Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age/gender as follows: - ≤ 0.6 mg/dL (for patients 1 to < 2 years old) - ≤ 0.8 mg/dL (for patients 2 to < 6 years old) - ≤ 1 mg/dL (for patients 6 to < 10 years old) - ≤ 1.2 mg/dL (for patients 10 to < 13 years old) - ≤ 1.4 mg/dL (for female patients ≥ 13 years old) - ≤ 1.5 mg/dL (for male patients 13 to < 16 years old) - ≤ 1.7 mg/dL (for male patients ≥ 16 years old) - Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 times upper limit of normal for age - Serum albumin ≥ 2 g/dL - Corrected QT interval (QTc) < 450 msec on ECG - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception - Able to swallow crushed or whole tablets - Body surface area ≥ 0.65 m^2 (for patients at dose level -1, 1, and 2) - No uncontrolled infection, including patients with known active HIV or chronic hepatitis - No patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study PRIOR CONCURRENT THERAPY: - Fully recovered from the acute toxic effects of all prior anticancer therapy - At least 6 months since prior total-body irradiation (TBI), craniospinal radiotherapy, or radiotherapy to ≥ 50% of the pelvis - At least 3 months since prior stem cell transplantation or rescue without TBI and no evidence of active graft-vs-host disease - At least 6 weeks since other substantial bone marrow radiation - At least 3 weeks since prior myelosuppressive therapy (6 weeks for nitrosourea) (for patients with solid tumors) - At least 2 weeks since prior local palliative radiotherapy (small port) - At least 2 weeks since prior cytoxic chemotherapy (for patients with leukemia or MPNs) - Hydroxyurea may be initiated and continued for up to 24 hours before the start of study treatment - At least 2 weeks since prior long-acting hematopoietic growth factor (e.g., Neulasta) or 1 week for a short-acting growth factor - For agents that have known adverse events occurring beyond 1 week, this period must be extended beyond the time during which adverse events are known to occur (as discussed with the study chair) - At least 1 week since prior therapy with a biologic (antineoplastic) agent - For agents that have known adverse events occurring beyond 1 week, this period must be extended beyond the time during which adverse events are known to occur (as discussed with the study chair) - At least 3 half-lives of antibody since prior monoclonal antibody - No patients who have been on an increasing dose of corticosteroids for the past week - No other concurrent investigational drugs - No other concurrent anticancer agents, including chemotherapy, radiotherapy, immunotherapy, or biologic therapy - No concurrent systemic steroids (i.e., prednisone > 10 mg) - No concurrent aspirin > 150 mg/day - No concurrent medications for myelofibrosis (e.g., hydroxyurea, interferon, thalidomide, busulfan, lenalidomide, or anagrelide) - No concurrent cyclosporine, tacrolimus, or other agents to prevent graft-vs-host disease after bone marrow transplant or organ rejection after transplant
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