A Study to Evaluate the Efficacy and Safety of Vismodegib in Combination with Ruxolitinib versus Placebo and Ruxolitinib in Patients with Intermediate- or High-Risk Myelofibrosis

Phase 1

• Conditions: Intermediate- or high-risk myelofibrosis; MedDRA version: 19.1Level: PTClassification code 10028537Term: MyelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-001620-33-DE
• Lead Sponsor: F. Hoffmann-La Roche Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-09-16
• Last Update Posted: 10 July 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 104

Inclusion Criteria

- Pathologically confirmed diagnosis of primary myelofibrosis (PMF), post-polycythemia vera (PV) MF, or post-essential thrombocythemia (ET) MF, according to the 2008 revised WHO criteria
- Intermediate-1, intermediate-2, or high risk according to the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Dynamic International Prognostic Scoring System (DIPSS)
Patients in the intermediate-1-risk group because of age alone (i.e., patients >= 65 years old with no other risk factors) are not eligible
- In the investigator’s judgment, requires treatment for MF
- Age >=18 years
- Life expectancy of >=6 months
- Peripheral blood blast count of <10%
- Palpable splenomegaly of >5 cm below the left costal margin
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
- All non-hematological adverse events must have resolved to NCI CTCAE Grade <=2 prior to starting therapy
- Adequate hepatic and renal function:
. Total bilirubin =<2.0 × upper limit of normal (ULN), unless resulting from hemolysis and Gilbert’s Syndrome
. AST and ALT =<2.5 ×ULN (= 5 ×ULN if liver is involved by extramedullary hematopoiesis as determined by investigator)
. Serum creatinine =<1.5 × ULN and creatinine clearance >30 milliliter/minute
- Documented negative serum or urine pregnancy test for women of
childbearing potential and use of two forms of acceptable contraception,
including one highly effective contraceptive method plus a barrier
method with spermicide. Contraception must be used while the patient is
enrolled in the study and for 24 months after the last dose of vismodegib
- For men with female partners of childbearing potential, agreement to
use a latex condom and to advise their female partners to use an
additional method of contraception during the study and for 2 months or
3 months after the last dose of vismodegib, depending on the country
- Male patients must agree not to donate sperm during the study and for
at least 2 months or 3 months after the last dose of vismodegib,
depending on the country
- All patients must agree not to donate blood or blood products during
treatment and for 24 months after the last dose of vismodegib
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 52
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 52

Exclusion Criteria

- Prior treatment with a Hedgehog (Hh) or Janus kinase (JAK) pathway inhibitor
- Treatment with strong CYP3A4 inhibitors/inducers within 28 days prior to Day 1
- Prior therapy for the treatment of intermediate- or high-risk MF within 28 days prior to Day 1
- Prior splenectomy or splenic irradiation
- Inadequate bone marrow reserve
- Patients with any history of platelet counts of < 50,000/microliter or absolute neutrophil count of < 500/microliter, except during treatment for myeloproliferative neoplasm (MPN) or treatment with cytotoxic therapy for any other reason
- Pregnant, lactating, or intending to become pregnant during the study
- Patients who refuse to potentially receive blood products and/or have a severe hypersensitivity to blood products
- Planned allogeneic bone marrow transplant during the study
- Known history of HIV
- Chronic active or acute viral hepatitis A, B or C infection
- Patients with suspected active or latent tuberculosis
- History of other malignancy that could affect compliance with the protocol or interpretation of results
- Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator’s judgment, precludes the patient’s safe participation in and completion of the study
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infections at study enrollment or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization within 28 days prior to Day 1

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified