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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Leukemia; Chronic Myelomonocytic Leukemia
• Intervention / Treatment: Drug: Ruxolitinib

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center and Research Institute
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • New York
    • New York, New York, United States, 10021
      • Weill Medical College of Cornell University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 3) 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response	Number 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.	At week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival will be from first dose of study drug until failure or death from any cause.	Up to 2 years
Duration of Response	Duration of response measured using time to AML transformation according to WHO Critieria	Up to 2 years
Time to Acute Myeloid Leukemia (AML) Transformation	Time to AML transformation according to World Health Organization (WHO) Critieria	Every 6 months after conclusion of treatment until end of study (40.3 months)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in symptom score	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)	Baseline, Week 17
Pathological Response	>/- 35% decrease in splenic volume as measured by CT scan	Baseline, Week 17
Mutational Status	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.	Baseline up to end of study (24 months)

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: Incyte Corporation
• Investigators: Principal Investigator: Eric Padron, MD, H. Lee Moffitt Cancer Center and Research Institute

Publications and helpful links

Helpful Links

• Moffitt Cancer Center Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2019
• Primary Completion (Actual): September 19, 2022
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: October 25, 2018
• First Submitted That Met QC Criteria: October 25, 2018
• First Posted (Actual): October 29, 2018

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: CMML
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myeloid; Chronic Disease; Leukemia; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile
• Other Study ID Numbers: MCC-19727

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No