MF, Myelofibrosis
Conditions
Keywords
Myelofibrosis, RUXOLITINIB, Autologous stem cell transplant
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.
Interventions
DRUGRUXOLITINIB / 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).
DRUGFilgrastim
Peripheral blood stem cells (PBSC) will be mobilized with filgrastim 10 mcg/kg/day IV
DRUGBusulfan
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
Sponsors
Incyte Corporation
Marina Kremyanskaya
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| CD34 cells | 4 years | Total CD34+ cell dose will be calculated based on results of flow cytometric analysis and patient's weight. |
| The regimen related mortality (RRM) | day 100 | — |
| Rate of engraftment/graft failure | 4 years | — |
| 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 |
| The incidence of serious infectious complications | up to 1 year post transplant | — |
| 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 |
| Change in FISH allele | at 365 days post-transplant | Changes in FISH abnormalities when present will be measured by cytogenetics. |
| Time of engraftment for neutrophils and platelets | 4 years | — |
Outcome results
None listed