Ruxolitinib in Combination With Autotransplant

Myelofibrosis Clinical Trial

Official title:

Ruxolitinib in Combination With High Dose Therapy and Autologous Stem Cell Transplantation for Myelofibrosis

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02469974
• Other study ID #: GCO 14-2106
• Status: Withdrawn
• Phase: N/A
• First received: May 28, 2015
• Last updated: August 11, 2016
• Start date: May 2015
• Est. completion date: August 2016

Study information

• Verified date: August 2016
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• MF
• Myelofibrosis
• Primary Myelofibrosis

Intervention

Drug:
• 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).
• Filgrastim
Peripheral blood stem cells (PBSC) will be mobilized with filgrastim 10 mcg/kg/day IV
• 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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Marina Kremyanskaya	Incyte Corporation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of combining ruxolitinib with autologous HSCT measured by graft failure or death	Safety of this approach as measured by graft failure or death	2 years	Yes
Secondary	CD34 cells	Total CD34+ cell dose will be calculated based on results of flow cytometric analysis and patient's weight.	4 years	No
Secondary	The regimen related mortality (RRM)		day 100	No
Secondary	The regimen related mortality (RRM)		day 365	No
Secondary	Rate of engraftment/graft failure		4 years	No
Secondary	Time of engraftment for neutrophils and platelets		4 years	No
Secondary	The incidence of serious infectious complications		up to 1 year post transplant	No
Secondary	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	at 180 and 365 days post-transplant	No
Secondary	Change in FISH allele	Changes in FISH abnormalities when present will be measured by cytogenetics.	at 365 days post-transplant	No
Secondary	Change in JAK allele	Changes in Jak 2 V617F allele burden when present will be measured by quantitative RT-PCR	at 365 days post-transplant	No
Secondary	Rate of response	Overall efficacy will be rated on a scale as complete remission, partial remission, clinical improvement, or stable disease	at 6 months post-transplant	No
Secondary	Rate of response	Overall efficacy will be rated on a scale as complete remission, partial remission, clinical improvement, or stable disease	at 1 year post-transplant	No