Clinical trial NCT02469974: Ruxolitinib in Combination With Autotransplant
Official title: Ruxolitinib in Combination With High Dose Therapy and Autologous Stem Cell Transplantation for Myelofibrosis
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Myelofibrosis
MF
Keywords: Myelofibrosis
RUXOLITINIB
Autologous stem cell transplant
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: Incyte Corporation
First posted: 2015-06-12
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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:

  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

Primary outcomes:
measure: Safety of combining ruxolitinib with autologous HSCT measured by graft failure or death
timeFrame: 2 years
Secondary outcomes:
measure: CD34 cells
timeFrame: 4 years
measure: The regimen related mortality (RRM)
timeFrame: day 100
measure: The regimen related mortality (RRM)
timeFrame: day 365
measure: Rate of engraftment/graft failure
timeFrame: 4 years
measure: Time of engraftment for neutrophils and platelets
timeFrame: 4 years
measure: The incidence of serious infectious complications
timeFrame: up to 1 year post transplant
measure: Changes in marrow fibrosis score
timeFrame: at 180 and 365 days post-transplant
measure: Change in FISH allele
timeFrame: at 365 days post-transplant
measure: Change in JAK allele
timeFrame: at 365 days post-transplant
measure: Rate of response
timeFrame: at 6 months post-transplant
measure: Rate of response
timeFrame: at 1 year post-transplant
Other outcomes:
Locations:
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Marina Kremyanskaya, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: