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出境医 / 临床实验 / Ruxolitinib for the Treatment of Chronic Myelomonocytic Leukemia (CMML): A Phase 2 Expansion

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

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
Chronic Myelomonocytic Leukemia Leukemia Drug: Ruxolitinib Phase 2

Study Design
Layout table for study information
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 : May 1, 2022
Estimated 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 Name: Jakafi
Outcome Measures
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.


Eligibility Criteria
Layout table for eligibility information
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.
Contacts and Locations

Contacts
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Contact: Rahil Ismail 813-745-3825 Rahil.Ismail@moffitt.org

Locations
Layout table for location information
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Rahil Ismail    813-745-3825    Rahil.Ismail@moffitt.org   
Principal Investigator: Eric Padron, MD         
Sub-Investigator: Rami Komrokji, MD         
Sub-Investigator: Jeffrey E Lancet, MD         
Sub-Investigator: Kendra Sweet, MD         
Sub-Investigator: Bijal Shah, MD         
Sub-Investigator: David Sallman, MD         
Sub-Investigator: Chetasi Talati, MD         
Sub-Investigator: Andrew Kuykendall, MD         
Sub-Investigator: Timothy Kubal, MD         
United States, Maryland
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21231
Contact: Tracy Graham    410-955-7593    Tgraham8@jhmi.edu   
Contact: Colin Huck    410-614-3725    Chuck1@jhmi.edu   
Principal Investigator: Amy DeZern, MD         
Sub-Investigator: Gabriel Ghiaur, MD         
Sub-Investigator: Ivana Gojo, MD         
Sub-Investigator: Mark Lewis, MD         
Sub-Investigator: Gabrielle Prince, MD         
Sub-Investigator: Lukasz Gondek, MD         
Sub-Investigator: Douglas Smith, MD         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Margaret Geisler    617-632-4912    margaretb_geisler@dfci.harvard.edu   
Contact: Anna Colbert    617-632-6363    Annaj_Colbert@dfci.hardvard.edu   
Principal Investigator: Marlise Luskin, MD         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Mikkael A Sekeres, MD, MS    216-445-9353    sekerem@ccf.org   
Sub-Investigator: Anjali Advani, MD         
Sub-Investigator: Aaron Gerds, MD, MS         
Sub-Investigator: Sudipto Mukherjee, MD, PhD, MPH         
Sub-Investigator: Aziz Nazha, MD         
Sub-Investigator: Hetty Carraway, MD         
Sub-Investigator: Ronald Sobecks, MD         
Sub-Investigator: Betty Hamilton, MD         
Sub-Investigator: Yogen Sauntharaarajah, MD, PhD         
Sub-Investigator: Barb Tripp, CNS         
Sub-Investigator: Bhumika Patel, MD         
Sub-Investigator: Jaroslaw Maciejewski, MD, PhD         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Incyte Corporation
Investigators
Layout table for investigator information
Principal Investigator: Eric Padron, MD H. Lee Moffitt Cancer Center and Research Institute
Tracking Information
First Submitted Date  ICMJE October 25, 2018
First Posted Date  ICMJE October 29, 2018
Last Update Posted Date March 26, 2021
Actual Study Start Date  ICMJE August 28, 2019
Estimated Primary Completion Date May 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 25, 2018) 		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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2018)
  • 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
  • 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.
  • Duration of Response [ Time Frame: Up to 2 years ]
    Duration of response measured using time to AML transformation according to WHO Critieria
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 26, 2018)
  • 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)
  • Pathological Response [ Time Frame: Baseline, Week 17 ]
    >/- 35% decrease in splenic volume as measured by CT scan
  • 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.
Original Other Pre-specified Outcome Measures
 (submitted: October 25, 2018)
  • 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)
  • Pathological Response [ Time Frame: Baseline, Week 17 ]
    >/- 35% decrease in splenic volume as measured by CT scan
  • 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.
 
Descriptive Information
Brief Title  ICMJE Ruxolitinib for the Treatment of Chronic Myelomonocytic Leukemia (CMML): A Phase 2 Expansion
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Myelomonocytic Leukemia
  • Leukemia
Intervention  ICMJE Drug: Ruxolitinib
Ruxolitinib 5 mg tablets, 4 per dose
Other Name: Jakafi
Study Arms  ICMJE 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.
Intervention: Drug: Ruxolitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 25, 2018) 		29
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 1, 2024
Estimated Primary Completion Date May 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Rahil Ismail 813-745-3825 Rahil.Ismail@moffitt.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03722407
Other Study ID Numbers  ICMJE MCC-19727
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party H. Lee Moffitt Cancer Center and Research Institute
Study Sponsor  ICMJE H. Lee Moffitt Cancer Center and Research Institute
Collaborators  ICMJE Incyte Corporation
Investigators  ICMJE
Principal Investigator: Eric Padron, MD H. Lee Moffitt Cancer Center and Research Institute
PRS Account H. Lee Moffitt Cancer Center and Research Institute
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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