Trial Ruxolitinib and Peg-interferon Alpha-2a Combination in Patients With Primary Myelofibrosis RUXOPeg

NCT02742324 | Completed Phase 1 DMC

• 1 other identifier: RUXOPeg
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

Phase 1/2, open-label, multi-center, trial, aiming at to identify the most efficacious dose combination that also satisfies certain safety requirements. It consists in a dose finding study to assess the safety of the combination of different doses of both ruxolitinib and peg-IFN alpha-2a, and a secondary randomized evaluation of the optimal doses found in the first part of the study to a total maximal number of 42 evaluable patients.

Conditions

Myelofibrosis

Keywords

efficacy; safety

Outcome Measures

Primary Outcomes (2)

• study treatment efficacy/safety phase I

  Phase 1 tolerance criterion : Occurrence of dose limiting toxicities DLT within the first 45 days

  day 45

• study treatment efficacy/safety phase II

  Phase II Efficacy criterion: Occurrence of at least 50% reduction in spleen length as measured by palpation within the first 6 months after randomization

  month 6

Secondary Outcomes (1)

• molecular response

  12 months

Study Arms (1)

Ruxolotinib and peg-IFN alpha -2a

EXPERIMENTAL

Phase I LeveL 1 Ruxolotinib 10 mg BID and peg-IFN alpha -2a 45 mcg weekly increasing doses to level 9 : Ruxolotinib 20 mg BID and peg-IFN alpha -2a 135 mcg weekly Phase II Ruxolotinib and peg-IFN alpha -2a randomized between selected doses from phase I

Drug: Ruxolotinib; Drug: peg-IFN alpha -2a

Interventions

Ruxolotinib DRUG

Ruxolitinib is administered orally twice a day (bid) everyday in 28-day treatment cycles. The starting dose is 10 mg BID and may go up to 20 mg BID. Ruxolotinib therapy starts on Cycle 1 day 1.

Also known as: Jakavi

Ruxolotinib and peg-IFN alpha -2a

peg-IFN alpha -2a DRUG

Peg-IFN-alpha-2a is administered subcutaneously once a week. The doses tested are 45, 90 and 135 mcg/week. .Peg-IFN-alpha-2a therapy starts at Cycle 1Day 15.Of note, Peg-IFN-alpha-2a will only be started if the platelet count is ≥ 50x109/L at C1D15.

Also known as: Pegasys

Ruxolotinib and peg-IFN alpha -2a

Eligibility Criteria

• Age: 18 Years - 66 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years and \< 66 years
• Diagnosis of primary or secondary myelofibrosis according to the 2008 World Health Organization (WHO) criteria for PMF (Tefferi and Vardiman 2008) and the proposed criteria for PPV-MF and PET-MF outlined by the International Working Group for Myelofibrosis Research and Treatment (Barosi et al 2008)
• Patients classified as high risk, OR intermediate risk-2, OR intermediate risk-1, as defined by the International Working Group, IWG (Cervantes, et al 2009) at diagnosis (or by the DIPSS (Passamonti et al. 2010) for patients assessed after diagnosis of PMF)
• Need for active therapy, defined as presence of at least one of the following:
• symptomatic splenomegaly
• presence of constitutional symptoms
• anemia (Hb\< 10g/dl)
• leukocytosis \> 25 G/l
• thrombocytosis \> 400 G/l
• Presence of JAK2V617F , Calreticulin or MPL mutations
• Platelet counts ≥ 150 x 109/L not reached with the aide of transfusions at screening
• Patients with ANC ≥ 1.5 x 109/L at screening without the use of G-CSF
• Peripheral blood blast count of ≤ 10% at Screening
• ECOG performance status of 0, 1, or 2 at Screening
• Negative serological Hepatitis B test (i.e. HBsAg negative and anti-HBc negative, patients positive for anti-HBc may be included if PCR for HBV DNA is negative); negative testing of Hepatitis C RNA; negative HIV test within 6 weeks prior to registration.

You may not qualify if:

• ANC \< 1.5 G/l or platelets \< 150 G/l
• \> 10% circulating blasts
• Contra-indication to IFN alpha or to ruxolitinib
• Patients previously treated with IFN alpha or a JAK2 inhibitor
• Documented autoimmune disease at screening or in the medical history
• History or presence of depression requiring treatment with antidepressant
• Evidence of severe retinopathy (e.g. cytomegalovirus retinitis, macular degeneration) or clinically relevant ophthalmological disorder (due to diabetes mellitus or hypertension)
• Thyroid dysfunction not adequately controlled
• Women of childbearing potential who have a positive serum pregnancy test at screening or who cannot or do not wish to use an effective method of contraception, during treatment and for 75 days after the last dose of study drug.
• Pregnant or nursing (lactating) women
• Patients with known active hepatitis B or C or with known HIV positivity
• Patient with a concurrent malignancy or malignancy within 3 years of Screening, with the exception of adequately treated basal or squamous cell carcinoma, non melanomatous skin cancer or curatively resected cervical cancer.
• Patient has a history of cardiac dysfunction including any of the following:
• Myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function
• History of documented congestive heart failure (New York Heart Association functional classification III-IV)

Sponsors & Collaborators

• French Innovative Leukemia Organisation: lead

Study Sites (1)

FILO French Innovative Leukemia Organization

Tours, 37044, France

Location

Related Links

• FILO internet site

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

ruxolitinib; peginterferon alfa-2a

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Jean Jacques KILADJIAN, MD PD

  FIM/GOELAMS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2016
• First Posted: April 19, 2016
• Study Start: March 1, 2016
• Primary Completion: December 30, 2021
• Study Completion: December 31, 2021
• Last Updated: July 27, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will share

Locations

FR (1)