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

NCT ID: NCT01164163

Last Updated: 2014-10-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30

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.

Detailed Description

OBJECTIVES:

Primary

• To estimate the maximum-tolerated dose and/or recommended phase II dose of oral JAK inhibitor INCB18424 administered continuously, twice daily to pediatric patients with relapsed or refractory solid tumors.
• To define and describe the toxicities of this treatment administered on this schedule in pediatric patients with relapsed or refractory solid tumors, leukemias, or myeloproliferative neoplasms (MPNs).
• To characterize the pharmacokinetics of this treatment in pediatric patients with relapsed or refractory solid tumors, leukemias, or MPNs.

Secondary

• To preliminarily define the antitumor activity of this treatment within the confines of a phase I study.
• To assess the biologic activity of oral JAK inhibitor INCB18424 upon JAK-STAT signaling in pediatric patients with relapsed or refractory solid tumors, leukemias, or MPNs.
• To assess the cytotoxicity and biologic activity of oral JAK inhibitor INCB18424 upon phosphosignaling and mutation burden in pediatric patients whose leukemias or MPNs have known CRLF2 and/or JAK mutations.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive oral JAK inhibitor INCB18424 twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients with relapsed or refractory leukemia may receive intrathecal chemotherapy in course 2 and subsequent courses at the discretion of the treating physician.

Plasma, bone marrow, and blood samples may be collected at baseline, during course 1, and before subsequent courses for pharmacokinetic analysis and correlative biology studies.

After completion of study treatment, patients are followed up for 30 days.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (Ruxolitinib)

Group Type: EXPERIMENTAL

ruxolitinib phosphate

Intervention Type: DRUG

laboratory biomarker analysis

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

Interventions

ruxolitinib phosphate

Intervention Type: DRUG

laboratory biomarker analysis

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Children's Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mignon Loh, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

UAB Comprehensive Cancer Center

Birmingham, Alabama, United States

Children's Hospital of Orange County

Orange, California, United States

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Children's Hospital Colorado Center for Cancer and Blood Disorders

Aurora, Colorado, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

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

Atlanta, Georgia, United States

Children's Memorial Hospital - Chicago

Chicago, Illinois, United States

Riley's Children Cancer Center at Riley Hospital for Children

Indianapolis, Indiana, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, United States

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

Boston, Massachusetts, United States

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

Ann Arbor, Michigan, United States

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Knight Cancer Institute at Oregon Health and Science University

Portland, Oregon, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

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

Dallas, Texas, United States

Baylor University Medical Center - Houston

Houston, Texas, United States

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

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

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

COG-ADVL1011

Identifier Type: OTHER

Identifier Source: secondary_id

ADVL1011

Identifier Type: -

Identifier Source: org_study_id