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Ruxolitinib in Combination With Autotransplant

Primary Purpose

Myelofibrosis, MF

Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
RUXOLITINIB / INC 424
Filgrastim
Busulfan
Sponsored by
Marina Kremyanskaya
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelofibrosis focused on measuring Myelofibrosis, RUXOLITINIB, Autologous stem cell transplant

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically documented diagnosis of MF (idiopathic or post PV/ET)
  • Age 18-75 years
  • Intermediate-2/ high-risk disease as per Dynamic IPSS (DIPSS) criteria or Intermediate-1 risk disease with one of the following features within one year from screening:

    1. Red cell transfusion dependency
    2. unfavorable Karyotype
    3. platelet count <100 x 109/L
    4. symptomatic splenomegaly
    5. PB blasts > 1%
    6. Blasts in PB <20% prior to study enrollment
    7. No available suitable matched related (6/6 or 5/6) or unrelated donor (8/8 or 7/8 allele matched) or unwilling or unable to pursue allogeneic stem cell transplant
    8. WBC <50,000/ml at screening
  • Able to give informed written consent
  • ECOG Performance status of 0-2
  • Life expectancy >6 months
  • Off all myelofibrosis-related investigational or standard agents (except for ruxolitinib) for at least 4 weeks prior to study enrollment and recovered from all toxicities. If patient is already on ruxolitinib for a minimum of 16 weeks prior to study enrollment, patient can proceed to mobilization and collection
  • Adequate organ function defined as the following (*unless clearly disease related):

    1. Adequate renal function - creatinine <2 x ULN
    2. Adequate hepatic function - AST/ALT <3 x ULN, Total Bilirubin <3 x ULN, exception is elevated indirect bilirubin attributed to Gilbert's syndrome or hemolysis
    3. Adequate hematopoietic function - Platelet ≥50 x 109/L (without transfusion) and ANC ≥1.0 x 109/L
    4. LVEF >40% (MUGA or echocardiogram)
    5. Adequate pulmonary function with DLCO >40%

Exclusion Criteria:

  • Hypersensitivity to JAK inhibitor
  • Clinical evidence of cirrhosis
  • Leukemic transformation (>20% blasts in PB or BM any time prior to HCT)
  • Platelet count <50 x 109/L
  • Active uncontrolled infection
  • History of another malignancy within 5-years of date of HCT except history of basal cell or squamous cell carcinoma of skin or PV or ET
  • Known HIV positive
  • Woman of childbearing potential unwilling or unable to use adequate contraception Pregnant or nursing females Known active infection with hepatitis A, B or C virus

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Ruxolitinib / INC 424

    Arm Description

    Ruxolitinib, Jakafi ®, will be given orally at standard dose daily for 16 weeks pre ASCT and up to 3 months post-ASCT for 10 patients (allowing for 2 additional screen failures). Patients will restart ruxolitinib at 100 days after the ASCT as long as their platelet count is at least 50 x103. For patients whose platelet count is below 50 x103 at day 100, ruxolitinib should be restarted once platelet count reaches 50 x103. The dose of ruxolitinib can be titrated up as per clinical guidelines. PBSC mobilization will include G-CSF 10 mcg/kg/day. HDC for ASCT will consist of IV busulfan 2.0 mg/KBW once daily x 4 for days -5 to -2.

    Outcomes

    Primary Outcome Measures

    Safety of combining ruxolitinib with autologous HSCT measured by graft failure or death
    Safety of this approach as measured by graft failure or death

    Secondary Outcome Measures

    CD34 cells
    Total CD34+ cell dose will be calculated based on results of flow cytometric analysis and patient's weight.
    The regimen related mortality (RRM)
    The regimen related mortality (RRM)
    Rate of engraftment/graft failure
    Time of engraftment for neutrophils and platelets
    The incidence of serious infectious complications
    Changes in marrow fibrosis score
    The myelofibrosis score will be assessed as per the European Consensus Grading published by Thiele Grading Description at 365 days as compared to 180 days
    Change in FISH allele
    Changes in FISH abnormalities when present will be measured by cytogenetics.
    Change in JAK allele
    Changes in Jak 2 V617F allele burden when present will be measured by quantitative RT-PCR
    Rate of response
    Overall efficacy will be rated on a scale as complete remission, partial remission, clinical improvement, or stable disease
    Rate of response
    Overall efficacy will be rated on a scale as complete remission, partial remission, clinical improvement, or stable disease

    Full Information

    First Posted
    May 28, 2015
    Last Updated
    August 11, 2016
    Sponsor
    Marina Kremyanskaya
    Collaborators
    Incyte Corporation
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02469974
    Brief Title
    Ruxolitinib in Combination With Autotransplant
    Official Title
    Ruxolitinib in Combination With High Dose Therapy and Autologous Stem Cell Transplantation for Myelofibrosis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2016
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    no enrollments
    Study Start Date
    May 2015 (undefined)
    Primary Completion Date
    August 2016 (Actual)
    Study Completion Date
    August 2016 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Marina Kremyanskaya
    Collaborators
    Incyte Corporation

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    To determine the safety of the approach of giving RUXOLITINIB before and after an autologous stem cell transplant, as measured by graft failure or death.
    Detailed Description
    This is a pilot, single arm, single center study with no stratification to assess the safety (measured by graft failure or death) and feasibility (measured by adequacy of stem cell collection) of combining ruxolitinib with autologous Hematopoeitic Stem Cell Transplantation (HSCT) in patients with advanced myelofibrosis (MF). Patients will receive a short course of ruxolitinib prior to and during mobilization of HSCT with Filgrastim. Conditioning for the autologous HSCT will consist of Bulsulfan. Post-transplant patients will receive ruxolitinib maintenance.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Myelofibrosis, MF
    Keywords
    Myelofibrosis, RUXOLITINIB, Autologous stem cell transplant

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Ruxolitinib / INC 424
    Arm Type
    Experimental
    Arm Description
    Ruxolitinib, Jakafi ®, will be given orally at standard dose daily for 16 weeks pre ASCT and up to 3 months post-ASCT for 10 patients (allowing for 2 additional screen failures). Patients will restart ruxolitinib at 100 days after the ASCT as long as their platelet count is at least 50 x103. For patients whose platelet count is below 50 x103 at day 100, ruxolitinib should be restarted once platelet count reaches 50 x103. The dose of ruxolitinib can be titrated up as per clinical guidelines. PBSC mobilization will include G-CSF 10 mcg/kg/day. HDC for ASCT will consist of IV busulfan 2.0 mg/KBW once daily x 4 for days -5 to -2.
    Intervention Type
    Drug
    Intervention Name(s)
    RUXOLITINIB / INC 424
    Other Intervention Name(s)
    RUX, Jakafi®
    Intervention Description
    Administered orally 5-20 mg twice daily x 16 weeks of therapy prior to attempted peripheral blood stem cells (PBSC) collection, during the collection and rest period and 3 months of therapy after high dose chemotherapy (HDC).
    Intervention Type
    Drug
    Intervention Name(s)
    Filgrastim
    Other Intervention Name(s)
    Neupogen®
    Intervention Description
    Peripheral blood stem cells (PBSC) will be mobilized with filgrastim 10 mcg/kg/day IV
    Intervention Type
    Drug
    Intervention Name(s)
    Busulfan
    Other Intervention Name(s)
    Busulfex®
    Intervention Description
    Conditioning for autologous Hematopoeitic Stem Cell Transplantation (HSCT) will consist of IV busulfan 2.0 mg/KBW once daily x 4 for days -5 to -2
    Primary Outcome Measure Information:
    Title
    Safety of combining ruxolitinib with autologous HSCT measured by graft failure or death
    Description
    Safety of this approach as measured by graft failure or death
    Time Frame
    2 years
    Secondary Outcome Measure Information:
    Title
    CD34 cells
    Description
    Total CD34+ cell dose will be calculated based on results of flow cytometric analysis and patient's weight.
    Time Frame
    4 years
    Title
    The regimen related mortality (RRM)
    Time Frame
    day 100
    Title
    The regimen related mortality (RRM)
    Time Frame
    day 365
    Title
    Rate of engraftment/graft failure
    Time Frame
    4 years
    Title
    Time of engraftment for neutrophils and platelets
    Time Frame
    4 years
    Title
    The incidence of serious infectious complications
    Time Frame
    up to 1 year post transplant
    Title
    Changes in marrow fibrosis score
    Description
    The myelofibrosis score will be assessed as per the European Consensus Grading published by Thiele Grading Description at 365 days as compared to 180 days
    Time Frame
    at 180 and 365 days post-transplant
    Title
    Change in FISH allele
    Description
    Changes in FISH abnormalities when present will be measured by cytogenetics.
    Time Frame
    at 365 days post-transplant
    Title
    Change in JAK allele
    Description
    Changes in Jak 2 V617F allele burden when present will be measured by quantitative RT-PCR
    Time Frame
    at 365 days post-transplant
    Title
    Rate of response
    Description
    Overall efficacy will be rated on a scale as complete remission, partial remission, clinical improvement, or stable disease
    Time Frame
    at 6 months post-transplant
    Title
    Rate of response
    Description
    Overall efficacy will be rated on a scale as complete remission, partial remission, clinical improvement, or stable disease
    Time Frame
    at 1 year post-transplant

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Histologically documented diagnosis of MF (idiopathic or post PV/ET) Age 18-75 years Intermediate-2/ high-risk disease as per Dynamic IPSS (DIPSS) criteria or Intermediate-1 risk disease with one of the following features within one year from screening: Red cell transfusion dependency unfavorable Karyotype platelet count <100 x 109/L symptomatic splenomegaly PB blasts > 1% Blasts in PB <20% prior to study enrollment No available suitable matched related (6/6 or 5/6) or unrelated donor (8/8 or 7/8 allele matched) or unwilling or unable to pursue allogeneic stem cell transplant WBC <50,000/ml at screening Able to give informed written consent ECOG Performance status of 0-2 Life expectancy >6 months Off all myelofibrosis-related investigational or standard agents (except for ruxolitinib) for at least 4 weeks prior to study enrollment and recovered from all toxicities. If patient is already on ruxolitinib for a minimum of 16 weeks prior to study enrollment, patient can proceed to mobilization and collection Adequate organ function defined as the following (*unless clearly disease related): Adequate renal function - creatinine <2 x ULN Adequate hepatic function - AST/ALT <3 x ULN, Total Bilirubin <3 x ULN, exception is elevated indirect bilirubin attributed to Gilbert's syndrome or hemolysis Adequate hematopoietic function - Platelet ≥50 x 109/L (without transfusion) and ANC ≥1.0 x 109/L LVEF >40% (MUGA or echocardiogram) Adequate pulmonary function with DLCO >40% Exclusion Criteria: Hypersensitivity to JAK inhibitor Clinical evidence of cirrhosis Leukemic transformation (>20% blasts in PB or BM any time prior to HCT) Platelet count <50 x 109/L Active uncontrolled infection History of another malignancy within 5-years of date of HCT except history of basal cell or squamous cell carcinoma of skin or PV or ET Known HIV positive Woman of childbearing potential unwilling or unable to use adequate contraception Pregnant or nursing females Known active infection with hepatitis A, B or C virus
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Marina Kremyanskaya, MD, PhD
    Organizational Affiliation
    Icahn School of Medicine at Mount Sinai
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Ruxolitinib in Combination With Autotransplant

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