Phase l/II Study of Ruxolitinib for Acute Leukemia

NCT01251965 | Terminated Phase 1 Results

• 2 other identifiers: 2010-0450NCI-2011-02439
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of ruxolitinib that can be given to patients with acute leukemia and to learn if the study drug can help control the disease. The safety of the drug will also be studied.

Conditions

Leukemia

Keywords

Relapsed Acute Leukemia; Acute myeloid leukemia; AML; Acute lymphocytic leukemia; ALL; Ruxolitinib; Jakafi; INC424; INCB018424

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicities (DLTs)

  MTD defined as highest dose level at which no more than one out of six subject experiences dose limiting toxicity (DLT) during first cycle (28 days) of therapy. A non-hematologic DLT defined as a clinically significant grade 3 or 4 adverse event or abnormal laboratory value (according to Common Toxicity Criteria for Adverse Effects (CTCAE) criteria) assessed as related to study drug (and unrelated to disease progression, intercurrent illness, or concomitant medications) occurring during first 28 days on study. Participants who received at least 80% of the originally assigned doses in the first cycle were evaluable for DLT assessment of each cohort.

  End of first 28 day cycle for toxicity

• Maximum Tolerated Dose (MTD) of Ruxolitinib

  The MTD is defined as the highest dose level at which no more than one out of six subject experiences DLT during the first cycle (28 days) of therapy.

  End of first 28 day cycle

Secondary Outcomes (1)

• Participants With a Response

  Up to 1 year

Study Arms (3)

Ruxolitinib 50 mg BID

EXPERIMENTAL

Phase I - Starting dose of Ruxolitinib 50 mg by mouth twice a day for 28 day cycle.

Drug: Ruxolitinib

Ruxolitinib 100 mg BID

EXPERIMENTAL

Phase I dose of Ruxolitinib 100 mg by mouth twice a day for 28 day cycle.

Drug: Ruxolitinib

Ruxolitinib 200 mg BID

EXPERIMENTAL

Phase I dose of Ruxolitinib 200 mg by mouth twice a day for 28 day cycle.

Drug: Ruxolitinib

Interventions

Ruxolitinib DRUG

Phase I - Starting dose of 50 mg by mouth twice a day for 28 day cycle. Phase II - MTD reached in Phase I.

Also known as: Jakafi, INCBO18424, INC424

Ruxolitinib 100 mg BID; Ruxolitinib 200 mg BID; Ruxolitinib 50 mg BID

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be \>14 years of age
• Must be diagnosed with refractory or relapsed AML or ALL.
• Must have adequate organ function as demonstrated by the following: o Alanine Aminotransferase (ALT) (SGOT) and/or Aspartate Aminotransferase (AST) (SGPT) equal to or less than 1.5x upper limit of normal o Serum creatinine equal to or less than 2.5 mg/dL
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
• At least 2 weeks from prior leukemia-directed treatment to starting treatment drug (except for hydroxyurea, which is allowed if clinically indicated but should be stopped after 2 weeks of receiving study drug, and glucocorticoids, which are allowed but should be stopped upon starting treatment drug).
• Treatment-related toxicities from prior therapies must have resolved to Grade equal to or less than 1 (except for peripheral neuropathy, which should resolve to grade equal to or less than 2)
• No active malignancies with the exception of basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
• Females of childbearing potential (FCBP)(A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) must have negative pregnancy test. FCBP and males participating in the study must agree to use a reliable form of contraception or to practice complete abstinence from heterosexual intercourse while participating in the study and for at least 28 days after discontinuation from the study. If pregnancy or a positive pregnancy test does occur in a study subject, treatment with the study drug must be immediately discontinued.

You may not qualify if:

• Known positive status for HIV, or known active hepatitis A, B, or C infection.
• Any serious medical condition or psychiatric illness that would prevent, (as judged by the treating physician) the subject from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Pregnant or lactating females.
• Acute promyelocytic leukemia
• Concurrent use of strong inducers or strong inhibitors of cytochrome P450 3A4 (CYP3A4). Strong inducers are rifampin and St. John's Worth. Strong inhibitors are HIV-antivirals, clarythromycin, itraconazole, ketoconazole, nefazodone, and telithromycin.
• Participating in any other research trial.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Incyte Corporation: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Pemmaraju N, Kantarjian H, Kadia T, Cortes J, Borthakur G, Newberry K, Garcia-Manero G, Ravandi F, Jabbour E, Dellasala S, Pierce S, Verstovsek S. A phase I/II study of the Janus kinase (JAK)1 and 2 inhibitor ruxolitinib in patients with relapsed or refractory acute myeloid leukemia. Clin Lymphoma Myeloma Leuk. 2015 Mar;15(3):171-6. doi: 10.1016/j.clml.2014.08.003. Epub 2014 Sep 17.

  PMID: 25441108 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Srdan Verstovsek, Professor, Leukemia
• Organization: The University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-7734

Study Officials

• Srdan Verstovsek, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Model Details: Phase I is a standard 3+3 design and will be used to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD), and no formal evaluation of efficacy (response rate will be implemented. Patients in Phase I part who were treated at the MTD will be included toward patients assessed for response in the phase II stage.

Study Record Dates

• First Submitted: November 30, 2010
• First Posted: December 2, 2010
• Study Start: December 1, 2010
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: June 8, 2025
• Results First Posted: September 6, 2019

Record last verified: 2025-05

Locations

US (1)