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Trial record 1 of 1 for:    s1712
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Testing the Addition of Ruxolitinib to the Usual Treatment (Tyrosine Kinase Inhibitors) for Chronic Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT03654768
Recruitment Status : Recruiting
First Posted : August 31, 2018
Last Update Posted : November 18, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group

Tracking Information
First Submitted Date  ICMJE August 29, 2018
First Posted Date  ICMJE August 31, 2018
Last Update Posted Date November 18, 2020
Actual Study Start Date  ICMJE July 20, 2018
Estimated Primary Completion Date January 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 29, 2018)
Rate of molecular response 4.5 (MR4.5) [ Time Frame: At 12 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 15, 2020)
  • Overall survival [ Time Frame: From the date of randomization until death from any cause with observations censored at the date of last contact for patients last known to be alive, assessed up to 5 years ]
    Will be estimated using the Kaplan-Meier method.
  • Progression-free survival [ Time Frame: From the date of randomization on study until the first of treatment failure/loss of response, progression, or death from any cause, assessed up to 5 years ]
    Will be estimated using the Kaplan-Meier method.
  • Incidence of adverse events [ Time Frame: Up to 5 years ]
    Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. CTCAE version 5.0 will be utilized for serious adverse events reporting only.
  • MR4.5 attainment and failure [ Time Frame: Up to 12 months ]
    Will be summarized descriptively
  • Molecular rate 4.0 (MR 4.0) attainment and failure [ Time Frame: Up to 12 months ]
    Will be summarized descriptively
  • Drug compliance [ Time Frame: Up to 5 years ]
    Will be summarized descriptively
  • BCR-ABL/BCR analysis [ Time Frame: Up to 5 years ]
    Linear regression models will be used to assess associations between treatment arm and the quantitative endpoint.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 29, 2018)
  • Overall survival [ Time Frame: From the date of randomization until death from any cause with observations censored at the date of last contact for patients last known to be alive, assessed up to 5 years ]
    Will be estimated using the Kaplan-Meier method.
  • Progression-free survival [ Time Frame: From the date of randomization on study until the first of treatment failure/loss of response, progression, or death from any cause, assessed up to 5 years ]
    Will be estimated using the Kaplan-Meier method.
  • Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 5 years ]
  • MR4.5 attainment and failure [ Time Frame: Up to 12 months ]
    Will be summarized descriptively
  • Molecular rate 4.0 (MR 4.0) attainment and failure [ Time Frame: Up to 12 months ]
    Will be summarized descriptively
  • Drug compliance [ Time Frame: Up to 5 years ]
    Will be summarized descriptively
  • BCR-ABL/BCR analysis [ Time Frame: Up to 5 years ]
    Linear regression models will be used to assess associations between treatment arm and the quantitative endpoint.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Testing the Addition of Ruxolitinib to the Usual Treatment (Tyrosine Kinase Inhibitors) for Chronic Myeloid Leukemia
Official Title  ICMJE A Randomized Phase II Study of Ruxolitinib (NSC-752295) in Combination With BCR-ABL Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia (CML) Patients With Molecular Evidence of Disease
Brief Summary This randomized phase II trial studies how well ruxolitinib phosphate, and bosutnib, dasatinib, or nilotinib, work in treating patients with chronic myeloid leukemia. Chronic myeloid leukemia cells produce a protein called BCR-ABL. The BCR-ABL protein helps chronic myeloid leukemia cells to grow and divide. Tyrosine kinase inhibitors, such as bosutinib, dasatinib, and nilotinib, stop the BCR-ABL protein from working, which helps to reduce the amount of chronic myeloid leukemia cells in the body. Ruxolitinib is a different type of drug that helps to stop the body from making substances called growth factors. Chronic myeloid leukemia cells need growth factors to grow and divide. The addition of ruxolitinib to the tyrosine kinase inhibitor may or may not help reduce the amount of chronic myeloid leukemia cells in the body.
Detailed Description

PRIMARY OBJECTIVE:

I. To compare the rate of molecular response 4.5 (MR4.5) after 12 months of combination therapy with ruxolitinib phosphate (ruxolitinib) plus a tyrosine-kinase inhibitor (TKI) (bosutinib, dasatinib, or nilotinib) versus a TKI alone, based on local polymerase chain reaction (PCR) testing to measure BCR-ABL transcripts in chronic phase chronic myelogenous leukemia (CML) patients with molecular evidence of disease.

SECONDARY OBJECTIVES:

I. To estimate the frequency and severity of toxicities of each regimen in this patient population.

II. To estimate progression free survival and overall survival of each regimen in this patient population.

ADDITIONAL OBJECTIVES:

I. To describe patterns of MR4.5 and molecular response 4.0 (MR4.0) attainment and failure over the 3, 6, 9, and 12-month time points of each regimen in this patient population.

II. To evaluate drug compliance based on patient reported drug intake calendars in this patient population.

III. To describe the kinetics of response in this patient population (as measured by quantitative BCR-ABL/BCR ratio) in both arms over the 3, 6, 9, and 12-month time points.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive bosutinib orally (PO) daily or dasatinib PO daily or nilotinib PO twice daily (BID) on days 1-90. Treatment repeats every 90 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive ruxolitinib phosphate PO BID on days 1-90, and bosutinib PO daily or dasatinib PO daily or nilotinib PO BID on days 1-90. Treatment repeats every 90 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 2 years, and then annually up to 5 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Intervention  ICMJE
  • Drug: Bosutinib
    Given PO
    Other Names:
    • Bosulif
    • SKI 606
    • SKI-606
  • Drug: Dasatinib
    Given PO
    Other Names:
    • BMS-354825
    • Dasatinib Hydrate
    • Dasatinib Monohydrate
    • Sprycel
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Nilotinib
    Given PO
    Other Name: AMN 107 Base Form
  • Drug: Nilotinib Hydrochloride Monohydrate
    Given PO
    Other Names:
    • AMN107
    • Nilotinib Monohydrochloride Monohydrate
    • Tasigna
  • Drug: Ruxolitinib
    Given PO
    Other Names:
    • INCB-18424
    • INCB18424
    • Jakafi
    • Oral JAK Inhibitor INCB18424
  • Drug: Ruxolitinib Phosphate
    Given PO
    Other Names:
    • INCB-18424 Phosphate
    • Jakafi
Study Arms  ICMJE
  • Active Comparator: Arm I (dasatinib, nilotinib)
    Patients receive bosutinib PO daily or dasatinib PO daily or nilotinib PO BID on days 1-90. Treatment repeats every 90 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Bosutinib
    • Drug: Dasatinib
    • Other: Laboratory Biomarker Analysis
    • Drug: Nilotinib
    • Drug: Nilotinib Hydrochloride Monohydrate
  • Experimental: Arm II (ruxolitinib phosphate, dasatinib, nilotinib)
    Patients receive ruxolitinib phosphate PO BID on days 1-90, and bosutinib PO daily or dasatinib PO daily or nilotinib PO BID on days 1-90. Treatment repeats every 90 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Bosutinib
    • Drug: Dasatinib
    • Other: Laboratory Biomarker Analysis
    • Drug: Nilotinib
    • Drug: Nilotinib Hydrochloride Monohydrate
    • Drug: Ruxolitinib
    • Drug: Ruxolitinib Phosphate
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: August 29, 2018)
84
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 1, 2026
Estimated Primary Completion Date January 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must have a diagnosis of chronic phase chronic myeloid leukemia without any history of progression to accelerated or blast phase CML; no new bone marrow aspiration and biopsy is needed to prove diagnosis prior to randomization; however, documentation stating the patient is in chronic phase is required
  • Patients must have detectable BCR-ABL transcripts measured by reverse transcriptase (RT)-PCR at a clinical laboratory improvement act (CLIA)-approved laboratory and reported on the international scale (IS) with a value of > 0.0032% IS and =< 1.0% IS within 21 days prior to randomization; the RT-PCR assay must have the sensitivity to detect a 4.5 log reduction in BCR-ABL transcripts from 100% IS (0.0032% IS or lower)
  • Patients must have been receiving TKI treatment for CML for at least 12 months prior to randomization
  • Patients must be currently receiving treatment with bosutinib (within the allowable dose range of 200-500 mg daily), nilotinib (within the allowable dose range of 150-400 mg BID or a cumulative daily dose of 300-800 mg), or dasatinib (within the allowable dose range of 40-140 mg daily); they must have received their current TKI for a minimum of 6 months prior to randomization and must be expected to remain on the same TKI for the next 12 months
  • Patient must not have a history of resistance to any prior TKI drug; if patient has received more than one TKI, the reason for changing treatment must have been intolerance to the prior TKI and the treatment change must have occurred >= 6 months prior to randomization
  • Patients must not be receiving any other investigational agents
  • Patients must have complete history and physical examination within 28 days prior to randomization
  • If clinically indicated, patients must have corrected Fridericia's correction formula (QTcF) interval < 500 ms (by Fridericia calculation) on a 12-lead electrocardiography (EKG) within 7 days prior to randomization
  • Platelets >= 100,000/mm^3 (100.0 x 10^9/L) within 7 days prior to randomization
  • Absolute neutrophil count (ANC) > 1,000/mm^3 (1.0 x 10^9/L) within 7 days prior to randomization
  • Hemoglobin >= 8 g/dL within 7 days prior to randomization
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x institutional upper limit of normal (IULN) within 7 days prior to randomization
  • Total bilirubin =< 1.5 x IULN within 7 days prior to randomization (unless the patient has a known diagnosis of Gilbert's syndrome)
  • Serum creatinine =< 1.5 x IULN within 7 days prior to randomization
  • Prior malignancy is allowed providing it does not require concurrent therapy; exception: active hormonal therapy is allowed
  • Patients must not be pregnant or nursing due to the teratogenic potential of the drugs used on this study; women of child-bearing potential must have a negative serum pregnancy test within 7 days prior to randomization; women/men of reproductive potential must have agreed to use an effective contraceptive method during treatment and for 30 days after discontinuation of study drug; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
  • Patients known to be human immunodeficiency virus positive (HIV+) are eligible provided they meet all other eligibility criteria and have undetectable HIV viral loads on their most recent viral load test which must have been performed in the last 6 months
  • Specimens (peripheral blood) must be collected and submitted to a CLIA-approved laboratory, within 21 days prior to randomization; BCR-ABL transcripts must be measured using RT-PCR and results must be reported using the international scale; the RT-PCR assay must have the sensitivity to detect a 4.5 log reduction in BCR-ABL transcripts from 100% IS (must be able to detect 0.0032% IS or lower)
  • Patients must be offered participation in submission of specimens for central BCR-ABL quantification and banking for future specimens; this submission is highly encouraged as an important protocol endpoint; with patient's consent, specimens must be collected and submitted, within 21 days prior to randomization
  • Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
  • As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03654768
Other Study ID Numbers  ICMJE S1712
NCI-2017-02066 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
S1712 ( Other Identifier: SWOG )
S1712 ( Other Identifier: CTEP )
U10CA180888 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
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 Southwest Oncology Group
Study Sponsor  ICMJE Southwest Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Kendra L Sweet Southwest Oncology Group
PRS Account Southwest Oncology Group
Verification Date November 2020

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