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Ruxolitinib in Combination With Autotransplant

Sponsor
Marina Kremyanskaya (Other)
Overall Status
Withdrawn
CT.gov ID
NCT02469974
Collaborator
Incyte Corporation (Industry)
0
Enrollment
1
Arm
15
Duration (Months)

Study Details

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.

Condition or Disease Intervention/Treatment Phase
N/A

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
0 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Ruxolitinib in Combination With High Dose Therapy and Autologous Stem Cell Transplantation for Myelofibrosis
Study Start Date :
May 1, 2015
Actual Primary Completion Date :
Aug 1, 2016
Actual Study Completion Date :
Aug 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ruxolitinib / INC 424

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.

Drug: RUXOLITINIB / INC 424
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).
Other Names:
  • RUX
  • Jakafi®

    • Drug: Filgrastim
    Peripheral blood stem cells (PBSC) will be mobilized with filgrastim 10 mcg/kg/day IV
    Other Names:
  • Neupogen®

    • Drug: Busulfan
    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
    Other Names:
  • Busulfex®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Safety of combining ruxolitinib with autologous HSCT measured by graft failure or death [2 years]

      Safety of this approach as measured by graft failure or death

    Secondary Outcome Measures

    1. CD34 cells [4 years]

      Total CD34+ cell dose will be calculated based on results of flow cytometric analysis and patient's weight.

    2. The regimen related mortality (RRM) [day 100]

    3. The regimen related mortality (RRM) [day 365]

    4. Rate of engraftment/graft failure [4 years]

    5. Time of engraftment for neutrophils and platelets [4 years]

    6. The incidence of serious infectious complications [up to 1 year post transplant]

    7. Changes in marrow fibrosis score [at 180 and 365 days post-transplant]

      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

    8. Change in FISH allele [at 365 days post-transplant]

      Changes in FISH abnormalities when present will be measured by cytogenetics.

    9. Change in JAK allele [at 365 days post-transplant]

      Changes in Jak 2 V617F allele burden when present will be measured by quantitative RT-PCR

    10. Rate of response [at 6 months post-transplant]

      Overall efficacy will be rated on a scale as complete remission, partial remission, clinical improvement, or stable disease

    11. Rate of response [at 1 year post-transplant]

      Overall efficacy will be rated on a scale as complete remission, partial remission, clinical improvement, or stable disease

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Marina Kremyanskaya
    • Incyte Corporation

    Investigators

    • Principal Investigator: Marina Kremyanskaya, MD, PhD, Icahn School of Medicine at Mount Sinai

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Marina Kremyanskaya, Assistant Professor, Icahn School of Medicine at Mount Sinai
    ClinicalTrials.gov Identifier:
    NCT02469974
    Other Study ID Numbers:
    • GCO 14-2106
    First Posted:
    Jun 12, 2015
    Last Update Posted:
    Aug 12, 2016
    Last Verified:
    Aug 1, 2016
    Keywords provided by Marina Kremyanskaya, Assistant Professor, Icahn School of Medicine at Mount Sinai
    Myelofibrosis
    RUXOLITINIB
    Autologous stem cell transplant
    Additional relevant MeSH terms:
    Primary Myelofibrosis
    Busulfan

    Study Results

    No Results Posted as of Aug 12, 2016