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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00935987




Registration number
NCT00935987
Ethics application status
Date submitted
7/07/2009
Date registered
9/07/2009
Date last updated
1/02/2019

Titles & IDs
Public title
Safety and Efficacy Study of CYT387 in Primary Myelofibrosis (PMF) or Post-polycythemia Vera (PV) or Post-essential Thrombocythemia (ET)
Scientific title
A Phase I/II, Open-Label, Dose-Escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally-Administered CYT387 in Primary Myelofibrosis or Post-Polycythemia Vera or Post-Essential Thrombocythemia Myelofibrosis.
Secondary ID [1] 0 0
CCL09101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Myelofibrosis 0 0
Post-Polycythemia Vera Myelofibrosis 0 0
Post-Essential Thrombocythemia Myelofibrosis 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CYT387

Experimental: CYT387 -


Treatment: Drugs: CYT387
For the Part 1 dose-escalation portion of the study, patients will be assigned to dose levels in successive cohorts starting with a dose in the first cohort of 100 mg/day. CYT387 will be orally self-administered as a single daily dose beginning on Day 1 of the study, and thereafter at approximately the same time each day of the 28-day cycle. It is recommended that all doses be preceded by a 2-hour fast from food and beverages, and be followed by a 1-hour post-dose fast from food and beverages.
Twenty additional patients will be assigned to a 150 mg BID (twice daily) dosing schedule. CYT387 will be orally self-administered twice-daily with doses approximately 10-12 hours apart beginning on Day 1 of the study, and thereafter at approximately the same times each day of the 28-day cycle.
For the Part 2 dose confirmation portion of the study, patients will be assigned to either 150 mg or 300 mg QD (once daily) dose groups.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and tolerability, dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of orally-administered CYT387 in patients with PMF or post-ET/PV MF.
Timepoint [1] 0 0
Ongoing throughout therapy up until 30 days after last dose of CYT387
Primary outcome [2] 0 0
Objective Response Rate (ORR), as measured by complete response (CR) rate, partial response (PR) rate and clinical improvement (CI) rate according to International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) consensus criteria
Timepoint [2] 0 0
Baseline to study completion
Primary outcome [3] 0 0
Pharmacokinetics of CYT387 in patients with PMF or post-ET/PV MF
Timepoint [3] 0 0
Baseline to end of Cycle 1
Secondary outcome [1] 0 0
Effect of CYT387 on bone marrow or peripheral blood cytogenetic findings in patients with PMF or post-ET/PV MF.
Timepoint [1] 0 0
Baseline to study completion
Secondary outcome [2] 0 0
Effect of CYT387 on peripheral blood granulocyte JAK2V617F allele burden in patients with PMF or post-ET/PV MF.
Timepoint [2] 0 0
Baseline to study completion
Secondary outcome [3] 0 0
Effect of CYT387 on peripheral blood endogenous myeloid colony formation in patients with PMF or post-ET/PV MF.
Timepoint [3] 0 0
Baseline to study completion
Secondary outcome [4] 0 0
Effect of CYT387 on plasma levels of inflammatory, fibrogenic and angiogenic cytokines in patients with PMF or post-ET/PV MF
Timepoint [4] 0 0
Baseline to study completion
Secondary outcome [5] 0 0
Pharmacodynamic correlates of CYT387 activity in patients with PMF or post-ET/PV MF who are receiving treatment with CYT387.
Timepoint [5] 0 0
Baseline to Cycle 9

Eligibility
Key inclusion criteria
- Diagnosis of PMF or post-polycythemia Vera (PV) or post-essential Thrombocythemia (ET)
MF as per revised World Health Organization (WHO) criteria.

- High-risk or Intermediate-2 risk MF (as defined by the International Prognostic
Scoring System [IPSS]; Appendix 13.6); or intermediate-I risk MF (IPSS) associated
with symptomatic splenomegaly/hepatomegaly and/or unresponsive to available therapy.

- Must be at least 18 years of age with life expectancy of = 12 weeks.

- Must be able to provide informed consent and be willing to sign an informed consent
form.

- Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or
2.

- Must have evidence of acceptable organ function within 7 days of initiating study drug
as evidenced by the following:

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) = 2.5 x upper
limit of normal (ULN) (or = 5 x ULN if in the investigator's opinion the
elevation is due to extramedullary hematopoiesis)

- Bilirubin = 2.0 x ULN or direct bilirubin < 1.0

- Serum creatinine = 2.5 x ULN

- Absolute neutrophil count = 500/µL

- Platelet count = 50,000/µL

- Females of childbearing potential must have a negative pregnancy test within 4 days of
initiating study drug.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Any chemotherapy (eg, hydroxyurea), immunomodulatory drug therapy (eg, thalidomide),
immunosuppressive therapy, corticosteroids > 10 mg/day prednisone or equivalent, or
growth factor treatment (eg, erythropoietin) within 14 days prior to initiation of
study drug.

- Incomplete recovery from major surgery within four weeks of study entry.

- Radiation therapy within four weeks of study entry.

- Women of childbearing potential, unless surgically sterile for at least 3 months (ie,
hysterectomy), OR postmenopausal for at least 12 months (FSH > 30 U/mL), OR unless
they agree to take appropriate precautions to avoid pregnancy (with at least 99%
certainty) from screening through end of study. Permitted methods for preventing
pregnancy must be communicated to study subjects and their understanding confirmed.

- Men who partner with a woman of childbearing potential, unless they agree to take
appropriate precautions to avoid pregnancy (with at least 99% certainty) from
screening through to the end of study. Permitted methods for preventing pregnancy must
be communicated to study subjects and their understanding confirmed.

- Females who are pregnant or are currently breastfeeding.

- Known positive status for HIV.

- Clinically active hepatitis B or C.

- Diagnosis of another malignancy unless free of disease for at least three years
following therapy with curative intent. Patients with early-stage basal cell or
squamous cell skin cancer, cervical intraepithelial neoplasia, cervical carcinoma in
situ or superficial bladder cancer may be eligible to participate at the
Investigator's discretion.

- Any acute active infection.

- Cardiac dysrhythmias requiring treatment, or prolongation of the QTc (Fridericia)
interval to > 450 msec for males or > 470 msec for females at prestudy screening,
unless attributable to pre-existing bundle branch block.

- Presence of = Grade 2 peripheral neuropathy.

- Uncontrolled congestive heart failure (New York Heart Association Classification 3 or
4), uncontrolled or unstable angina, myocardial infarction, cerebrovascular accident,
or pulmonary embolism within 3 months prior to initiation of study drug.

- Uncontrolled inter current illness or any concurrent condition that, in the
Investigator's opinion, would jeopardize the safety of the patient or compliance with
the protocol.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2012
Sample size
Target
Accrual to date
Final
166
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
Minnesota
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
Canada
State/province [5] 0 0
Quebec

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sierra Oncology LLC - a GSK company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study seeks to (i) determine a safe and tolerated dose of CYT387 (momelotinib) given to
patients with PMF, post-PV or post-ET and, (ii) assess the effectiveness of
orally-administered CYT387 as a treatment for PMF, post-PV or post-ET.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00935987
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ayalew Tefferi, MD
Address 0 0
Mayo Clinic
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00935987