Ruxolitinib in Combination With Autotransplant

NCT ID: NCT02469974

Last Updated: 2016-08-12

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2016-08-31

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.

Conditions

Myelofibrosis; MF

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

RUXOLITINIB / INC 424

Intervention Type: DRUG

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).

Filgrastim

Intervention Type: DRUG

Peripheral blood stem cells (PBSC) will be mobilized with filgrastim 10 mcg/kg/day IV

Busulfan

Intervention Type: DRUG

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

Interventions

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).

Intervention Type: DRUG

Filgrastim

Peripheral blood stem cells (PBSC) will be mobilized with filgrastim 10 mcg/kg/day IV

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

RUX; Jakafi®; Neupogen®; Busulfex®

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Incyte Corporation

INDUSTRY

Sponsor Role: collaborator

Marina Kremyanskaya

OTHER

Sponsor Role: lead

Responsible Party

Marina Kremyanskaya

Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Marina Kremyanskaya, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Other Identifiers

GCO 14-2106

Identifier Type: -

Identifier Source: org_study_id