Clinical Trials /

Ruxolitinib Phosphate and Dasatinib or Nilotinib in Treating Patients With Chronic Myeloid Leukemia

NCT03654768

Description:

This randomized phase II trial studies how well ruxolitinib phosphate and dasatinib or nilotinib work in treating patients with chronic myeloid leukemia. Ruxolitinib, dasatinib, and nilotinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ruxolitinib Phosphate and Dasatinib or Nilotinib in Treating Patients With Chronic Myeloid Leukemia
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: S1712
  • SECONDARY ID: NCI-2017-02066
  • SECONDARY ID: S1712
  • SECONDARY ID: S1712
  • SECONDARY ID: U10CA180888
  • NCT ID: NCT03654768

Conditions

  • Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Interventions

DrugSynonymsArms
DasatinibBMS-354825, SprycelArm I (dasatinib, nilotinib)
NilotinibAMN 107 Base FormArm I (dasatinib, nilotinib)
Ruxolitinib PhosphateINCB-18424 Phosphate, JakafiArm II (ruxolitinib phosphate, dasatinib, nilotinib)

Purpose

This randomized phase II trial studies how well ruxolitinib phosphate and dasatinib or nilotinib work in treating patients with chronic myeloid leukemia. Ruxolitinib, dasatinib, and nilotinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Description

      PRIMARY OBJECTIVES:

      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)
      (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.

      TERTIARY OBJECTIVES:

      I. To describe patterns of MR4.5 and molecular rate 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 dasatinib orally (PO) daily or nilotinib PO twice daily (BID) on days
      1-90. Treatment repeats every 90 days for up to 4 courses in the absence of disease
      progression or unacceptable toxicity.

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

      After completion of study treatment, patients are followed up for up to 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (dasatinib, nilotinib)Active ComparatorPatients receive dasatinib PO daily or nilotinib PO BID on days 1-90. Treatment repeats every 90 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
  • Dasatinib
  • Nilotinib
Arm II (ruxolitinib phosphate, dasatinib, nilotinib)ExperimentalPatients receive ruxolitinib phosphate PO BID on days 1-90 and dasatinib PO daily or nilotinib PO BID on days 1-90. Treatment repeats every 90 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
  • Dasatinib
  • Nilotinib
  • Ruxolitinib Phosphate

Eligibility Criteria

        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 baseline (at least 0.0032% IS)

          -  Patients must be receiving treatment with dasatinib (within the allowable dose range
             of 70-100 mg daily) or nilotinib (within the allowable dose range of 200-400 mg BID)
             as first or second line therapy for a minimum of 6 months prior to registration

          -  Patients must not have received > 2 TKIs for treatment of CML (hydroxyurea prior to
             initiation of TKI is allowed)

               -  Patients must have been on their current TKI for a minimum of 6 months prior to
                  randomization

               -  If dasatinib or nilotinib is second-line therapy, the reason for stopping
                  first-line treatment must not have been resistance to prior treatment or failure
                  to achieve an adequate response on their first-line TKI (e.g., the patient could
                  have stopped due to intolerance to prior TKI)

          -  Patients must have been receiving TKI treatment for CML for at least one year and no
             more than 10 years prior to randomization

          -  Patients must be expected to remain on the same TKI for the next 12 months

          -  Patients must not be receiving any other investigational agents

          -  Patients must have complete history and physical examination within 28 days prior to
             randomization

          -  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

          -  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; 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

          -  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 baseline (at least 0.0032% IS)

          -  Patients must be offered participation in submission of specimens for central BCR-ABL
             quantification; 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 offered participation in specimen banking for future research; with
             patient?s consent, specimens must be submitted

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of molecular response 4.5 (MR4.5)
Time Frame:At 12 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:Will be estimated using the Kaplan-Meier method.
Measure: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
Safety Issue:
Description:Will be estimated using the Kaplan-Meier method.
Measure:Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:MR4.5 attainment and failure
Time Frame:Up to 12 months
Safety Issue:
Description:Will be summarized descriptively
Measure:Molecular rate 4.0 (MR 4.0) attainment and failure
Time Frame:Up to 12 months
Safety Issue:
Description:Will be summarized descriptively
Measure:Drug compliance
Time Frame:Up to 5 years
Safety Issue:
Description:Will be summarized descriptively
Measure:BCR-ABL/BCR analysis
Time Frame:Up to 5 years
Safety Issue:
Description:Linear regression models will be used to assess associations between treatment arm and the quantitative endpoint.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Southwest Oncology Group

Last Updated