Ruxolitinib in Combination With Autotransplant

Marina Kremyanskaya

Status: Withdrawn

Conditions: Myelofibrosis; MF

Treatments: Drug: Busulfan; Drug: Filgrastim; Drug: RUXOLITINIB / INC 424

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02469974

GCO 14-2106

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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0 participants in 1 patient group

Ruxolitinib / INC 424

Experimental group

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.

Treatment:

Drug: RUXOLITINIB / INC 424

Drug: Filgrastim

Drug: Busulfan