Back to resultsRuxolitinib 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Withdrawn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
About this trial
This is an interventional treatment trial for Myelofibrosis focused on measuring Myelofibrosis, RUXOLITINIB, Autologous stem cell transplant
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
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
NCT ID
NCT02469974
First Posted
May 28, 2015
Last Updated
August 11, 2016
Sponsor
Marina Kremyanskaya
Collaborators
Incyte Corporation
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
We'll reach out to this number within 24 hrs