Ruxolitinib for the Treatment of Chronic Myelomonocytic Leukemia (CMML): A Phase 2 Expansion

H. Lee Moffitt Cancer Center and Research Institute (Other)
Overall Status
Active, not recruiting ID
Incyte Corporation (Industry)

Study Details

Study Description

Brief Summary

This study is to find out if treating Chronic Myelomonocytic Leukemia (CMML) with a study drug (ruxolitinib) can improve outcomes of patients with CMML.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Anticipated Enrollment :
29 participants
Intervention Model:
Sequential Assignment
None (Open Label)
Primary Purpose:
Official Title:
A Sequential Two-Stage Dose Escalation Study to Evaluate the Safety and Efficacy of Ruxolitinib for the Treatment of Chronic Myelomonocytic Leukemia (CMML): A Phase 2 Expansion
Actual Study Start Date :
Aug 28, 2019
Anticipated Primary Completion Date :
Sep 19, 2022
Anticipated Study Completion Date :
May 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ruxolitinib

All patients will be given their first dose of oral Ruxolitinib, 20 mg at first scheduled visit. After that dose and on all other days patients will self-administer oral Ruxolitinib at a dose of 40 mg daily divided into two equal doses approximately 12 hours apart. Patients will be treated for a total of 16 weeks. After treatment, patients will be followed monthly.

Drug: Ruxolitinib
Ruxolitinib 5 mg tablets, 4 per dose
Other Names:
  • Jakafi
  • Outcome Measures

    Primary Outcome Measures

    1. Overall Response [At week 16]

      Proportion of participants achieving clinical benefit defined as hematologic improvement, complete remission, partial remission, or stable disease by the International Working Group Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN) Criteria.

    Secondary Outcome Measures

    1. Time to Acute Myeloid Leukemia (AML) transformation [Every 6 months after conclusion of treatment until end of study (24 months)]

      Time to AML transformation according to World Health Organization (WHO) Critieria

    2. Overall Survival [Up to 2 years]

      Overall survival will be from first dose of study drug until failure or death from any cause.

    3. Duration of Response [Up to 2 years]

      Duration of response measured using time to AML transformation according to WHO Critieria

    Other Outcome Measures

    1. Change in symptom score [Baseline, Week 17]

      Change in symptom score as defined by the Myeloproliferative Neoplasms Symptom Assessment Form-Total Symptom Score (MPN-SAF TSS). The MPN -SAF TSS scores symptoms of myeloproliferative neoplasm by rankings of 0 (symptom is absent) to 10 (Worst imaginable)

    2. Pathological Response [Baseline, Week 17]

      >/- 35% decrease in splenic volume as measured by CT scan

    3. Mutational Status [Baseline up to end of study (24 months)]

      Mutational Status in CMML patients measured by sanger sequencing of JAK2, c-CBL, N-RAS, K-RAS, RUNX-1, TET2, SRSF2, EZH2, ASXL1 and DNMT3a.

    Eligibility Criteria


    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Accepts Healthy Volunteers:
    Inclusion Criteria:
    • Confirmed diagnosis of Chronic Myelomonocytic Leukemia (CMML)using the World Health Organization (WHO) classification.

    • 18 years of age or older at the time of obtaining informed consent.

    • Must be able to adhere to the study visit schedule and other protocol requirements.

    • Participants must be able to provide adequate BM aspirate and biopsy specimens for histopathological analysis and standard cytogenetic analysis during the screening procedure.

    • An Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 is required.

    • Women of childbearing potential must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse 1) for at least 28 days before starting study drug; 2) while participating in the study; and

    1. for at least 28 days after discontinuation from the study.
    • Must understand and voluntarily sign an informed consent form.

    • Must have a life expectancy of greater than 3 months at time of screening.

    • Must have symptomatic splenomegaly and/or an Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score >17.

    Exclusion Criteria:
    • Any of the following lab abnormalities: Platelet count of less than 35,000/uL, Absolute Neutrophil Count (ANC) less than 250/uL, Serum Creatinine ≥ 2.0, Serum total bilirubin >1.5x ULN

    • Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of CMML within 28 days of the first day of study drug treatment.

    • Prior history of metastatic malignancy in past 2 years

    • Any serious medical condition or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he/she participates in the study.

    • Concurrent use of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF). Granulocyte Colony Stimulating Factor (G-CSF) could be used for the short-term management of neutropenic infection. Stable doses of erythropoietin stimulating agents that were started >8 weeks from first ruxolitinib dose or corticosteroids that were being administered prior to screening are allowed.

    • Uncontrolled current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

    • Pregnant women are excluded from this study because ruxolitinib has not been studied in pregnant participants. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ruxolitinib, breastfeeding should be discontinued if the mother is treated with ruxolitinib.

    Contacts and Locations


    Site City State Country Postal Code
    1 H. Lee Moffitt Cancer Center and Research Institute Tampa Florida United States 33612
    2 Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Baltimore Maryland United States 21231
    3 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    4 Weill Medical College of Cornell University New York New York United States 10021
    5 Cleveland Clinic Cleveland Ohio United States 44195

    Sponsors and Collaborators

    • H. Lee Moffitt Cancer Center and Research Institute
    • Incyte Corporation


    • Principal Investigator: Eric Padron, MD, H. Lee Moffitt Cancer Center and Research Institute

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:


    None provided.
    Responsible Party:
    H. Lee Moffitt Cancer Center and Research Institute Identifier:
    Other Study ID Numbers:
    • MCC-19727
    First Posted:
    Oct 29, 2018
    Last Update Posted:
    Jun 10, 2022
    Last Verified:
    Jun 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Studies a U.S. FDA-regulated Device Product:
    Keywords provided by H. Lee Moffitt Cancer Center and Research Institute
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jun 10, 2022