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Ruxolitinib in Combination With Autotransplant

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ClinicalTrials.gov Identifier: NCT02469974
Recruitment Status : Withdrawn (no enrollments)
First Posted : June 12, 2015
Last Update Posted : August 12, 2016
Sponsor:
Collaborator:
Incyte Corporation
Information provided by (Responsible Party):
Marina Kremyanskaya, Icahn School of Medicine at Mount Sinai

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
Myelofibrosis MF Drug: RUXOLITINIB / INC 424 Drug: Filgrastim Drug: Busulfan Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
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 2015
Actual Primary Completion Date : August 2016
Actual Study Completion Date : August 2016


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 Name: 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 Name: Busulfex®




Primary Outcome Measures :
  1. Safety of combining ruxolitinib with autologous HSCT measured by graft failure or death [ Time Frame: 2 years ]
    Safety of this approach as measured by graft failure or death


Secondary Outcome Measures :
  1. CD34 cells [ Time Frame: 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) [ Time Frame: day 100 ]
  3. The regimen related mortality (RRM) [ Time Frame: day 365 ]
  4. Rate of engraftment/graft failure [ Time Frame: 4 years ]
  5. Time of engraftment for neutrophils and platelets [ Time Frame: 4 years ]
  6. The incidence of serious infectious complications [ Time Frame: up to 1 year post transplant ]
  7. Changes in marrow fibrosis score [ Time Frame: 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 [ Time Frame: at 365 days post-transplant ]
    Changes in FISH abnormalities when present will be measured by cytogenetics.

  9. Change in JAK allele [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: at 1 year post-transplant ]
    Overall efficacy will be rated on a scale as complete remission, partial remission, clinical improvement, or stable disease



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

    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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02469974


Sponsors and Collaborators
Marina Kremyanskaya
Incyte Corporation
Investigators
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Principal Investigator: Marina Kremyanskaya, MD, PhD Icahn School of Medicine at Mount Sinai
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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: June 12, 2015    Key Record Dates
Last Update Posted: August 12, 2016
Last Verified: August 2016
Keywords provided by Marina Kremyanskaya, Icahn School of Medicine at Mount Sinai:
Myelofibrosis
RUXOLITINIB
Autologous stem cell transplant
Additional relevant MeSH terms:
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Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Busulfan
Immunologic Factors
Physiological Effects of Drugs
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Myeloablative Agonists