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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03722407
Recruitment Status : Active, not recruiting
First Posted : October 29, 2018
Last Update Posted : June 10, 2022
Sponsor:
Collaborator:
Incyte Corporation
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

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
Chronic Myelomonocytic Leukemia Leukemia Drug: Ruxolitinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 29 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 : August 28, 2019
Estimated Primary Completion Date : September 19, 2022
Estimated Study Completion Date : May 1, 2024


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 Name: Jakafi




Primary Outcome Measures :
  1. Overall Response [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline, Week 17 ]
    >/- 35% decrease in splenic volume as measured by CT scan

  3. Mutational Status [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03722407


Locations
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United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
United States, Maryland
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
Weill Medical College of Cornell University
New York, New York, United States, 10021
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Incyte Corporation
Investigators
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Principal Investigator: Eric Padron, MD H. Lee Moffitt Cancer Center and Research Institute
Additional Information:
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Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT03722407    
Other Study ID Numbers: MCC-19727
First Posted: October 29, 2018    Key Record Dates
Last Update Posted: June 10, 2022
Last Verified: June 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
CMML
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases
Hematologic Diseases