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

NCT01164163 | Completed Phase 1 DMC

• 2 other identifiers: ADVL1011COG-ADVL1011
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 24

Brief Summary

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.

Conditions

Chronic Myeloproliferative Disorders; Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Unspecified Childhood Solid Tumor, Protocol Specific

Keywords

unspecified childhood solid tumor, protocol specific; recurrent childhood acute lymphoblastic leukemia; recurrent childhood acute myeloid leukemia; refractory chronic lymphocytic leukemia; relapsing chronic myelogenous leukemia; childhood myelodysplastic syndromes; previously treated myelodysplastic syndromes; atypical chronic myeloid leukemia, BCR-ABL1 negative; chronic myelomonocytic leukemia; juvenile myelomonocytic leukemia; myelodysplastic/myeloproliferative neoplasm, unclassifiable; polycythemia vera; essential thrombocythemia; childhood acute promyelocytic leukemia (M3); acute myeloid leukemia/transient myeloproliferative disorder; primary myelofibrosis

Outcome Measures

Primary Outcomes (3)

• Maximum-tolerated dose and/or recommended phase II dose

  28 days

• Toxicity

  30 days post treatment

• Pharmacokinetics

  Up to 28 days

Secondary Outcomes (2)

• Antitumor activity

  Up to 30 days post treatment

• Toxicity and biologic activity

  Day 1 and Day 15

Study Arms (1)

Treatment (Ruxolitinib)

EXPERIMENTAL

Drug: ruxolitinib phosphate; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

ruxolitinib phosphate DRUG

Treatment (Ruxolitinib)

laboratory biomarker analysis OTHER

Treatment (Ruxolitinib)

pharmacological study OTHER

Treatment (Ruxolitinib)

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Histologically confirmed diagnosis of one of the following: * Relapsed or refractory extracranial solid tumor * Relapsed or refractory leukemia * At least 25% blasts in the bone marrow (M3) with the exception of patients with acute myeloid leukemia (AML), who must have \> 20% blasts in the bone marrow * Relapsed or refractory 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 * Relapsed or refractory leukemia or MPN that have confirmed JAK mutations and/or positive TSLPR surface staining * Testing for JAK mutations and/or confirmed positive flow cytometry surface staining for the thymic stromal lymphopoietin receptor (TSLPR; encoded by CRLF2); eligibility for part C will be contingent upon patients demonstrating overexpression of CRLF2 by flow cytometric methods measured at either JHU or U. Washington flow laboratories (therefore, pre-enrollment samples need to be sent to one of these laboratories after discussion with Dr. Loh) or if the patient has a CLIA lab documented alteration in JAK1 or JAK2, SH2B3, IL7RA, or another gene that would predict sensitivity to JAK inhibition. * 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 known active CNS involvement (radiographic or cytologic) 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) * Not refractory to to red cell or platelet transfusion * 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 * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Able to swallow crushed or whole tablets * Nasogastric or G tube administration is not allowed * 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 2 weeks since prior local palliative radiotherapy (small port) * At least 6 months since prior total-body irradiation (TBI), craniospinal radiotherapy, or radiotherapy to ≥ 50% of the pelvis (for patients with solid tumors) * At least 3 months since prior TBI, craniospinal radiotherapy, or radiotherapy to ≥ 50% of the pelvis (for patients with leukemia) * 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 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 * Intrathecal cytarabine (Ara-C) is not myelosuppressive chemotherapy * Patients with leukemia are permitted to receive intrathecal chemotherapy, including methotrexate or cytarabine, only if this is given at the time of diagnostic lumbar puncture at least 24 hours prior to the start of INCB018424 * 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 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (24)

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35294, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Children's Hospital Colorado Center for Cancer and Blood Disorders

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus

Atlanta, Georgia, 30322, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60611, United States

Location

Riley's Children Cancer Center at Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, 20892-1182, United States

Location

Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

C.S. Mott Children's Hospital at University of Michigan Medical Center

Ann Arbor, Michigan, 48109-0286, United States

Location

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, 63110, United States

Location

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Knight Cancer Institute at Oregon Health and Science University

Portland, Oregon, 97239-3098, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, 75390, United States

Location

Baylor University Medical Center - Houston

Houston, Texas, 77030-2399, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

Midwest Children's Cancer Center at Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Myeloproliferative Disorders; Leukemia; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Polycythemia Vera; Thrombocythemia, Essential; Leukemia, Myeloid, Acute; Myeloproliferative Syndrome, Transient; Primary Myelofibrosis

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Neoplasms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders

Study Officials

• Mignon Loh, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2010
• First Posted: July 16, 2010
• Study Start: September 1, 2010
• Primary Completion: October 1, 2014
• Last Updated: October 23, 2014

Record last verified: 2014-10

Locations

US (24)